phd projects 2024

The 2024 PhD Project Annual Conference

March 21-22, 2024.

Hyatt Regency O'Hare

Please text PhdProject1 to 888-689-3135 to opt-in for Conference Updates.

Welcome to Set Your Course – Impact the Future!

Life Changing Moments Stories from PhD Project Business Faculty Members

Through conferences, mentoring, and networking, The PhD Project encourages and supports historically underrepresented candidates on their journey to acquiring a PhD. We are a critical bridge between businesses and our alumni PhDs and their students, providing connections to high-potential recruits. With demonstrated success in creating more diverse business faculty, we are doing more than transforming the face of business education. We are inspiring new generations of future leaders, bringing diversity to our workforce, and creating a better world for all of us.

Our History

Origins: How It Began

Living the dream a new generation of minority business school professors, following the dream, is this for me, sacrifice… or investment, finding a balance, living the dream, paying it forward creating tomorrow’s leader in business through academe, leading the way, changing the face of business education, changing the face of business research, influencing undergraduates, impacting the community.

Pave the way

Making an Impact Leveraging Leadership

One-on-one with phd project trailblazers, search for story.

Search for an Author, Institution, Organizations or Publication

2024 PhD Project Annual Conference

March 21-22, 2024

The flagship event for The PhD Project is our annual conference for potential doctoral students. At this 2-day conference, you can network with doctoral students, business school representatives, professors and sponsor organizations, all in one place.

Board of Directors PhD Project Staff
Our History
Member Stories
Hall of Fame
Is a PhD Right for You?
Doctoral Resources
Network of Support
Doctoral Student Associations
Faculty Networking Groups
Corporate Partners
University Partners
Strategic Alliances
Annual Conference

Building a stronger, more diverse workforce. Together.

We create the future

We empower our community, we believe diversity is crucial, why pursue a business phd.

There are many compelling reasons, including:

an MBA is not required, just the GMAT/GRE test score;
universities generally provide stipends and don’t charge tuition;
business experience is highly valued;
academic compensation packages are attractive

Dreams achieved

Meet our new faculty.

Andria Hill

University of Central Florida

Ryan Ballestero

University of Texas-Austin

Isaac Addae

Morgan State University

Lumumba Seegars

Harvard University

Karren Knowlton

University of Pennsylvania

Aziza Jones

Rutgers University

Summer Jackson

Hilda Carillo

University of South Florida

Michigan State University

Dorian Boncoeur

University of Texas at Dallas

Edwyna Hill

University of Georgia

Case Western Reserve University

Schools & departments

PhD Projects 2024

PhD Research Projects on offer at the IfA

At the Institute for Astronomy, we study every astronomical scale from the solar system up to the large-scale structure of the Universe. Listed below you will find the wide range of PhD projects that are offered for entry in September 2024. You will also find some short videos from supervisors that introduce their projects.

When you apply for a PhD place at the IfA , we strongly encourage you to select 4 projects from 4 different supervisors to maximize your chances for a good match. Those invited to interview will be given the opportunity to meet their selected supervisors either in-person or virtually. After the interview days have concluded, we will make offers matched to a specific project and supervisor.

Active Galactic Nuclei

Astrobiology, astronomical instrumentation computational astrophysics, galaxy formation & evolution, milky way & local universe, solar system.

Imperial College London Imperial College London

PhD Projects

Projects on offer for 2024 entry will be progressively added here in December and January. The projects themselves may evolve somewhat before October 2024.

We strongly encourage you to come to the open day on November 29th, 2023, to discuss the projects with potential supervisors. Information about the open day can be found here , under PhD opportunities. However, you do not need to specify projects/supervisors when you apply; you are free to describe your areas of interest in the application, and we will match you with suitable supervisors. You are welcome to contact academic staff members to discuss projects in more detail.

Theoretical Topics in Exoplanet Atmospheres - James Owen

Exoplanet discoveries of the last 30 years have taught us the planets are far more common and diverse than our Solar System led us to believe. From the original Hot Jupiters to the ubiquitous sub-Neptunes and the mysterious super-Earths, many problems about the origin and evolution abound. With the successful launch of JWST and the upcoming ARIEL mission, we now have a new way to explore exoplanets: by observing the properties and composition of their atmospheres. However, these new observations can only be interpreted in the framework of any theoretical model. At the moment, there is yet to be a clear picture of what knowledge of the composition of an exoplanet's atmosphere tells us. The structure, composition, cloud properties and dynamics of exoplanet atmospheres need to be better understood with many open theoretical problems. In this project, you will use analytical, numerical, and simulation methods to tackle these challenges head-on, guided by results from state-of-the-art JWST observations. Given the large number of open theoretical problems, you will be free to develop your research direction.

Finding The Most Distant Quasars With Euclid - Daniel Mortlock

The Euclid space telescope, which launched successfully in July 2023, is in the process of surveying one third of the sky, during which it will produce a catalogue with billions of detected astronomical sources. A few hundred of these will be quasars in the early Universe, seen as they were less than a billion years after the Big Bang, some of which will be beyond the current record of redshift z = 7.5. On the timescale of a PhD starting in October 2024 Euclid data will allow us to push our understanding of the quasar population back to redshift 9, which in turn will reveal the nature of the first super-massive black holes; this project will be based on the interpretation and analysis of this new data. As such the project sits at the interface between astronomy, statistics and data science, so would suit a student interested in these areas.

Disentangling stellar and planetary signals in exoplanet transits - Yvonne Unruh

Stellar magnetic activity introduces uncertainties and biases in the determination of exoplanet parameters, and disentangling the stellar from the planetary signal is critical if we want to study exoplanets. As stellar magnetic activity also leaves a trace in stellar spectra (through changes in spectral line shape and strength, as well as by modulating stellar granulation signals, stellar limb darkening and broad-band emergent intensities), it should be possible to remove the stellar signal from the planetary signal. The aim of this project is to do just that by identifying reliable tracers of stellar activity and developing models to remove the stellar from the planetary signal. You will be using radiative transfer codes to derive the emergent radiation from (magneto-convection) models of stellar surfaces with a range of activity levels.

Accurate cosmology with the Rubin LSST - Boris Leistedt

With its Legacy Survey of Space and Time (LSST), the Rubin Observatory (first light in 2027) will provide the widest and deepest measurements of the clustering and gravitational lensing of galaxies to date. Thanks to its high cadence, Rubin will also revolutionise transient science, for example detecting hundreds of thousands of supernovae type Ia. This PhD project will tackle the challenges of modeling the spatial distributions of the detected high-redshift galaxies and supernovae at the precision needed to harness their cosmological information. This will require developing innovative techniques to model and accurately propagate potential systematic uncertainties all the way from the processing of photometric images to the extraction of cosmological parameters. Machine learning is likely to play a big role in making these techniques computationally efficient, for example in accelerating image processing or simulations. Data from Rubin-like precursor surveys such as Hyper Supreme Cam Survey and the Dark Energy Survey will be employed as a testbed, in combination with valuable information (e.g., CMB lensing) from CMB experiments such as the Atacama Cosmology Telescope and the Simons Observatory.

Planet Formation in the Inner Regions of Protoplanetary Discs - Subhanjoy Mohanty

This PhD project will study the formation of planets in the inner regions of protoplanetary disks. Specifically, it will focus on modelling the growth of planetesimals and planetary embryos into full-fledged planets in the inner disk, via N-body simulations supplemented with the effects of interactions with gas. The successful applicant will have a strong background in undergraduate physics, including a solid understanding of undergraduate-level hydrodynamics, and good programming skills (e.g., in python).

Confronting the theory of exoplanet evolution with observations – James Kirk

Over the last 30 years 5500 extrasolar planets have been found orbiting stars beyond our solar system, with the vast majority orbiting extremely close to their host stars. These discoveries have fundamentally challenged our understanding of planet formation and evolution. Theory predicts that an exoplanet’s atmospheric composition depends on how and where the planet formed and that the extreme radiation suffered by close-in exoplanets leads to strong atmospheric winds and atmospheric loss. To robustly test these theories requires observations of the planets with the largest signals, “hot Jupiters”, which will pave the way for future observations of Earth-sized exoplanets. This project will combine the revolutionary sensitivity of the James Webb Space Telescope (JWST) with Hubble and ground-based data to measure the chemical compositions of hot Jupiters in unprecedented detail. In doing so, the project will perform robust tests of how and why hot Jupiters came to be and how their atmospheres respond to extreme irradiation.

Dusty Star-Forming Galaxies Near and Far - Dave Clements

The Herschel Space Observatory has revealed that galaxies containing substantial amounts of dust obscured star formation, so-called Dusty Star-Forming Galaxies (DSFGs), play a major role in the evolution of the galaxy population. However, these objects are hard to study in the optical and near-infrared since the large amounts of dust within them absorb light at these wavelengths and re-emit it at longer far-IR and submm wavelengths. Surveys with Herschel have revealed the DSFG population at large redshift, z~2-4, with some exceptional objects at still higher redshift. Studying these objects and determining their properties at other wavelengths will allow us to place them in the broader context of galaxy and large scale structure evolution: do they, for example, evolve into massive elliptical galaxies, and if so, do they lie in galaxy clusters or protoclusters at high redshift? What triggers their star formation activity - is it the result of galaxy interactions and mergers, as seen in the local universe, or are other factors such as cold gas flows from the cosmic web involved? What is their relationship to quasars and other types of active galaxy - in the local universe galaxy mergers are thought to trigger quasar-like activity; is this true for the Herschel high redshift DSFGs? What is the role of gravitational lensing in our view of these objects, and can this be used to study the less luminous but far more numerous underlying population of dusty galaxies? New data from our own observations and from large projects such as Euclid and JWST surveys will be used to answer these questions. At the same time, new insights into the DSFGs’ local counterparts, Ultraluminous Infrared Galaxies (ULIRGs), are becoming possible thanks to the new generation of submm instruments. Recent observations led by the Imperial Infrared group have detected polarised dust emission in the core of the nearest ULRG, Arp220, suggesting the presence of magnetic fields at the heart of this object. Is this true for other local ULIRGs, and what are the implications for these rapidly star forming galaxies? Meanwhile, a new generation of far-IR space missions are being proposed to NASA. Simulations and predictions of what these missions might find are needed to help develop their science cases and optimise their instruments. Our observations of DSFGs near and far will feed into this process and help set the scene for far-IR astronomy in the 2030s and beyond.

Past Projects

Exoplanets origins and evolution - Dr James Owen
Accretion discs around polluted white dwarfs - Dr Chris Manser and Dr James Owen
Atmospheres of Habitable Zone Exoplanets around M dwarfs - Dr Subhanjoy Mohanty
Epoch of Reionization with REACH and SKA - Dr Jonathan Pritchard
Cosmology with the CMB - Prof Andrew Jaffe and Prof Alan Heavens
The most luminous galaxies in the local Universe - Dr Dave Clements
Astrophysics and cosmology from the 21cm line - Dr Jonathan Pritchard
Cosmology with the next generation of CMB experiments - Prof Andrew Jaffe
Planet formation and habitability - Dr Subu Mohanty
The first quasars and supermassive Black Holes - Dr Daniel Mortlock
Bayesian Analysis of the dynamic Universe - Dr Florent Leclercq and Prof Alan Heavens
Bayesian analysis of weak gravitational lensing - Prof Alan Heavens and Prof Andrew Jaffe
Searching for the most distant quasars - Dr Daniel Mortlock
Higgs, Dark Matter and the Global Search for Physics beyond the Standard Model - Dr Pat Scott
Direct Detection of Dark Matter and Global Fits - Prof Roberto Trotta
Cosmology and Fundamental Physics with Euclid - Prof Roberto Trotta
Extreme Dusty Star-Forming Galaxies - Dr Dave Clements
The Nature and Evolution of 70 micron selected galaxies - Dr Dave Clements
The X-ray-Starburst Connection in the Herschel Era - Dr Dave Clements
Advanced statistical methods for astrophysical probes of dark energy - Prof Roberto Trotta
The early Universe and cosmological parameters from the Cosmic Microwave Background, Gravitational Waves, and other observations - Professor Andrew Jaffe
Determining the topology of the Universe from the Cosmic Microwave Background - Professor Andrew Jaffe
Accretion Disks, Planet Formation and Habitability Around Red and Brown Dwarfs - Dr Subu Mohanty
Towards optimal statistics of reionization a5 Emulating radiation from variable stars - Dr Yvonne Unruh nd the 21 cm signal - Dr Jonathan Pritchard
Cool pre-main sequence stars: their surfaces and circumstellar environments - Dr Yvonne Unruh
Understanding solar brightness changes on climate-relevant time scales - Dr Yvonne Unruh
Gravitational lensing, dark matter, and black holes - Professor Steve Warren
The most luminous galaxies in the local Univers e - Dr Dave Clements
Pushing the limits of high-z LSS structure cosmology - Dr Boris Leistedt
Emulating radiation from variable stars - Dr Yvonne Unruh
Cosmology with likelihood-free inference - Prof Alan Heavens
The highest redshift quasars - Professor Stephen Warren
Planet Formation in the Inner Disc-The First End to End Model - Dr Subu Mohanty
Stellar Brightness Variability and Exoplanets – Dr Yvonne Unruh
The Earliest Stages of Planet Formation - Dr Richard Booth
Molecules in the Atmosphere of Venus - Dr David Clements and Dr Ingo Mueller

PhD projects 2024

Many of our PIs are recruiting doctoral candidates in this year's application round. Below you can find their project proposals or research descriptions. Get inspired by these to draft the research proposal for your application. Your research proposal should be longer than the summary provided here (approximately 2-3 pages) and should show some of your own input, including a title, a short background of the topic, a research question, proposed methods and references. Moreover, we encourage you to explain how you plan to include both sides of the experimental-theoretical spectrum in your project. For instance, how could laboratory experiments help support the conclusions of your bioinformatics project? Which bioinformatics tools do you plan to include in your wet laboratory project?

[NEW] - Co-evolution of transposable element activity and host genome

[NEW] - Understanding the Distribution of Mutations along Genomes

[NEW] - Chromatin regulation in stem cells and development

[NEW] - Molecular mechanisms of genome transcription regulation & dysregulation

[NEW] - Investigating Antisense Oligonucleotide (ASO) Treatments for Neurodegenerative Diseases

[NEW] - Transcriptional condensates

[NEW] - Computational systems medicine and disease control

[NEW] - Comparative Analysis of DNA Methylome Conservation Across Species

[NEW] - Genome Regulation Department

[NEW] - Synthetic biology of long-range gene regulation

[NEW] - lncRNAs in 3D – dissecting the gene regulatory function of long non-coding RNAs

[NEW] - Evolution of primate transcription factor genes

Mathematical modelling of cis-regulatory landscapes

[NEW] - Epigenetic mechanisms controlling cell fate decisions during the early stage of liver, pancreas and biliary tree development

[NEW] - Transcriptional Regulation Group

[NEW] - Molecular mechanisms of bacterial immunity

PhD Projects

Our researchers belong to one of four research centres that investigate problems using different approaches. Many of our projects are cross-disciplinary, with advisors from different centres, giving you the benefit of a wider range of expertise.

Our PhD projects are divided into 'Earmarked PhD Projects' and 'Standard PhD Projects'. Please select a Centre to explore all available PhD projects in that category. Subscribe to alerts to be notified of any new PhD projects and for any queries, please contact the HDR Liaison Officer, [email protected] .

Subscribe to alerts PhD Homepage

Standard PhD Projects

All standard PhD projects qualify for a UQ Graduate School Scholarship . Those marked with an asterisk (*) qualify for an additional scholarship, the IMB Global Challenges Scholarship , which is a top-up to the UQ Graduate School Scholarship (projects that qualify will be announced soon). This year's theme for Global Challenges Scholarship projects is 'Drugs inspired by nature'.

When you have chosen a project (or wish to devise a new project), please contact the Principal Advisor via email ensuring the project title (or proposed project title) is in the subject line and your latest CV is attached. Once you have confirmation that they will endorse you for your project, you may officially apply via the UQ Application Portal making sure you select 'UQ Graduate School Scholarship' when you do so.

Centre for Cell Biology of Chronic Diseases
Centre for Chemistry and Drug Discovery
Centre for Superbug Solutions
Centre for Population and Disease Genomics

A new strategy to treat chronic liver disease

Principal Advisor: Prof Irina Vetter (IMB)

Associate Advisor: A/Prof Frederic Gachon (IMB)

Non-alcoholic fatty liver disease (NAFLD) is a severe health burden which can progress to cirrhosis and hepatocellular carcinoma. Associated with obesity and a sedentary lifestyle, NAFLD affects around 25% of the world’s population and up to 90% of people with morbid obesity. To date, there are no treatment possibilities available for NAFLD and therapeutic strategies are highly sought after. We recently demonstrated that the size of the liver fluctuates over the day. These daily fluctuations are regulated by circadian and feeding rhythms and accompany the daily rhythms of nutrient storage, drug detoxification and ribosome biogenesis. While high amplitude circadian rhythms are associated with a healthy liver, the rhythmicity of liver size and physiology are attenuated in obesity and liver disease. Our preliminary data suggests that the regulation of ion channels play a role in liver size fluctuation and the development of liver fibrosis. This project aims at identifying new small molecules targeting these ion channels to target liver size with the aim to restore normal liver physiology and counteract the development or even cure NAFLD, opening new avenues for treatment and prevention of NAFLD.

AI and Mechanical Ventilation

Principal Advisor: Professor John Fraser ( [email protected] )

Associate Advisor: TBC

To test the effect of introduction of AI algorithms to help analyse ventilator waveforms and data from the mechanical ventilator. This will include the testing of feasibility and safety, and impact on clinical decision making.

Bioengineering of novel nanovesicles for drug delivery

Principal Advisor: Professor Rob Parton ( [email protected] )

Associate Advisor: Dr Ye-Wheen Lim ( [email protected] )

How are nanoparticles transported across different biological barriers from the bloodstream to their target sites? This project will use tumor xenograft models and live imaging in the zebrafish to uncover the trafficking of nanoparticles in a live organism.

De-risking the drug development pipeline by finding biomarkers of drug action

Principal Advisor: Associate Professor Nathan Palpant ( [email protected] )

Associate Advisors: Dr Sonia Shah ( [email protected] ) and Professor Glenn King ( [email protected] )

Greater than 90% of drugs fail to advance into clinical approval. Genetic evidence supporting a drug-target-indication can improve the success by greater than 50%. This project aims to make use of consortium-level data resources (UKBiobank, Human Cell Atlas, ENCODE etc) to identify genetic links between genetic targets and phenotypes to help facilitate the translation of drugs from healthy individuals (Phase 1 clinical trial assessing safety) into sick patients (Phase 2 clinical trial assessing efficacy). Finding orthogonal biomarkers of drug action in healthy individuals is critical to de-risk drug dosing when transitioning from Phase 1 to Phase 2 trials. Using ASIC1a as a candidate drug being developed to treat heart attacks, this project will develop a functionally validated computational pipeline to predict orthogonal biomarkers of ASIC1a inhibitor drug action in healthy individuals to help inform dosing in human clinical trials. Computationally predicted biomarkers will be validated using genetic knockout animals and pharmacological inhibitors of ASIC1a. Collectively, this project will help develop proof-of-principle computational pipeline for orthogonal biomarker prediction of drug targets in the human genome.

*Designing mini-protein chaperones for dementia treatment

Principal Advisor: Dr Michael Healy ( [email protected] )

Associate Advisor: Professor Brett Collins ( [email protected] )

At the heart of neurodegeneration is the concept of proteostasis, the tight regulation of protein synthesis, transport, degradation, and recycling. Defective proteostasis results in the toxic accumulation of proteins and peptides such as amyloid β (Aβ) and phosphorylated tau. The major pathway that regulates proteostasis is the sorting and degradation of transmembrane proteins in the endolysosomal system, and associated autophagic and lysosomal destruction of toxic cytosolic molecules. Retromer is a trimeric protein complex that is a central player in regulating the endolysosomal system and is downregulated in the hippocampus of patients with Alzheimer’s disease. Molecules (termed molecular chaperones) that stabilise this complex increase Retromer levels in neurons and decrease levels of neurotoxic Aβ, however, to date no molecule has made it into the clinic. Here I will use our knowledge of fundamental Retromer biology to design a suite of ‘mini-protein’ molecular chaperones using revolutionary machine learning techniques (Alphafold, RFdiffusion) and test their ability to stabilise Retromer in vitro and reverse dysfunction in known cellular models of neurodegeneration. Unlike traditional drug screening approaches, these revolutionary techniques allow for the generation of novel protein backbones that bind to specified regions of a protein or protein complex. If successful, these molecular chaperones could represent novel therapeutics for the treatment of the underlying molecular pathology that is common in neurodegeneration.

*Qualifies for the Global Challenges Scholarship .

Developing new therapeutic and diagnostic tools for tissue ischemia

Associate Advisors: Professor Glenn King ( [email protected] )

The research project will test the hypothesis that acid sensing ion channel 1a (ASIC1a) mechanistically underpins ischemia-induced injury across diverse organs and thus provides both a diagnostic marker and a therapeutic target for tissue ischemia. While ischemic injuries to the heart and brain in the form of heart attack and stroke are the most significant contributors to the global burden of disease, all organs are susceptible to ischemic injury whether in the context of patient care or during the procurement and storage of organs for transplantation. My laboratory aims to accelerate the diagnosis and prevention of organ damage due to tissue ischemia. This project stems from our elucidation of ASIC1a as a novel target for ischemic injuries and our discovery of Hi1a, the most potent known inhibitor of this channel, from venom of an Australian funnel-web spider. In preclinical studies we showed that Hi1a is a safe and potent therapeutic that reduces brain injury after stroke, improves recovery after a heart attack, and enhances the performance of donor hearts procured for transplantation. These remarkable therapeutic properties stem from Hi1a’s ability to protect cells from ischemic injury by inhibiting ASIC1a. Exciting preliminary data demonstrating that Hi1a interacts only with ASIC1a in tissue regions experiencing acute ischemia and not in healthy or the remote zone of injured tissue. This presents a unique opportunity to develop Hi1a as a diagnostic tool (theranostic) to measure the progression of ischemic injuries using clinical imaging methods. This project will develop peptidic ASIC1a inhibitors as a diagnostic marker of tissue ischemia. We will develop radiolabelled peptides that bind to ASIC1a with high affinity to image the progression of organ ischemia in vivo using positron emission tomography-magnetic resonance imaging (PET-MRI). The project will also determine the temporal-spatial activation of ASIC1a-Hi1a interactions across organ systems in response to acute acidosis. Using a murine model of global hypercapnic acidosis, we will determine ASIC1a-Hi1a interactions at a tissue and sub-cellular level during acute ischemic stress to reveal the broader therapeutic landscape for ASIC1a inhibitors. The over-arching goal of this project is to understand the biology of ASIC1a stress response mechanisms across diverse organ systems.

Endometrial stem cell maturation and its role in reproductive disease

Principal Advisor: Dr Brett McKinnon (IMB)

Associate Advisor: A/Prof Emaneual Pelosi (UQ Centre for Clinical Research)

The endometrium is a key organ of the reproductive system. It is a complex biological structure of epithelial glands, vascularised stroma and infiltrating immune cells that require intimate communication for normal function. The endometrium is unique in that it undergoes cyclical shedding and regeneration each month regenerated from the resident mesenchymal stem and epithelial progenitor cells in the basalis layer. The maturation and differentiation of these cells into a fully functional endometrium must be tightly regulated. Variations in this maturation from stem cell to mature cell could lead to aberrant cell subsets that increase disease susceptibility and underpin disease variations.

We propose to apply complex organoid and translation models to study stem cell maturation in the endometrium, identify the relationship between altered maturation and molecular signatures of disease and identify the potential to personalise treatment based on these signatures. We will use a combination of single-cell and spatial multi-omics data to determine gene and protein expression and quantitative microscopy to map endometrial maturation and its relationship to reproductive disease. This project will develop skills in both wet-lab and dry-lab techniques incorporating experimental design, performance and data analysis.

*From Bugs to Drugs: Improving drug delivery into cancer and immune cells.

Principal Advisor: Professor Jennifer Stow ( [email protected] )

Associate Advisor: Professor Mark Schembri ( [email protected] ) and Professor Halina Rubinsztein-Dunlop (SMP; [email protected] )

The efficient delivery of drugs, vaccines, mRNAs and nanoparticles into human cells is still a major challenge for treating and preventing disease. Bugs, or bacteria, hold the key for penetrating our cells by hijacking endocytic, phagocytic and other trafficking pathways with their effector proteins. We can use these effectors too, to develop new methods for penetrating cancer cells and immune cells to improve drug delivery and to manipulate cell function and survival. Our bug-based effectors will be made, tagged and used for microscopy and live imaging of cells and for measuring biophysical properties of the cell membranes. We will explore effector-enhanced drug delivery and monitor disease processes in organoids and live tissues, in collaboration with microbiologists, physicists, immunologists and clinicians.

Endothelial stabilisation and resuscitation in septic shock

Associate Advisors: Dr Jacky Suen ( [email protected] ) and Dr Nchafatso Obonoyo ( [email protected] )

To investigate whether endothelial stabilisation and resuscitation in septic shock improves organ function.

How does abnormal light exposure affect Alzheimer’s disease progression?

Principal Advisor: Dr Benjamin Weger (IMB)

Associate Advisor: Dr Juergen Goetz (QBI); A/Prof Frederic Gachon (IMB)

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. One of the factors that may contribute to AD development and progression is chronodisruption, which occurs when the circadian clock is misaligned with the environmental light-dark cycle. This can happen due to shift work, aging, or exposure to aberrant light patterns. Chronodisruption can impair cognitive performance, mood, and sleep quality in people with AD. Moreover, it can precede the onset of clinical symptoms by several years. Bright light therapy has been shown to improve some of these aspects in AD patients, suggesting a causal link between light exposure, chronodisruption and AD.

In this project, we will use a mouse model of AD that exhibits early cognitive impairment and expose it to an aberrant light regimen that mimics the disrupted light environment often experienced by people with AD. We will assess the effects of this regimen on circadian rhythms, memory and learning abilities and molecular markers of AD pathology. This project will reveal how aberrant light exposure influences AD progression and provide insights for developing chronotherapeutic strategies that could slow down or prevent AD.

Hypothermic organ preservation (HOPE) to improve donor heart availability

Principal Advisor: Dr Jacky Suen ( [email protected] )

Associate Advisor: Professor John Fraser ( [email protected] )

Donor hearts are extremely sensitive to time once extracted from donor, with increasing time directly associated with increased graft dysfunction and patient mortality. The PhD fellow will work with leading clinical scientists in cardiac transplantation to push the boundary of donor heart preservation. Our previous work has extended the allowable storage time from 4 to 8 hours. This PhD will be the first worldwide to examine the feasibility to further extend this beyond 12 hours. This study is funded by an NHMRC Ideas grant.

Identifying vascular cell types and genes involved in human skeletal disease

Principal Advisor: Dr John Kemp (IMB)

Associate Advisor: Dr Anne Lagendijk (IMB); Dr Dylan Bergen (University of Bristol, UK)

Genetic association studies offer a means of identifying drug targets for disease intervention. However, few of the causal genes underlying skeletal disease associations have been identified and functionally validated in vivo. Our team has developed a workflow that integrates genetic association study results, single-cell transcriptomics, and phenotype data from knockout animal models to identify disease-causing genes and predict the cellular context through which they function. Unpublished results from our team suggest that vascular cell-specific genes have underappreciated roles in bone homeostasis. This PhD project aims to better understand how vascular genes contribute to the development of skeletal disease. Research objectives: (i) To define a single-cell RNA sequencing census of different cell types, present in the bone microenvironment of zebrafish, and contrast the transcriptomic profiles of different bone cells across mice, and humans. (ii) Investigate whether profiles of different bone cell types are conserved across species, and whether vascular cell types are also enriched for skeletal disease associated genes. (iii) Identify candidate vascular cell-specific genes (and drug targets) and validate their predicted roles in skeletal disease using zebrafish knockout models and live imaging to monitor vessel network formation and function.

Impact of the sex-specific growth hormone secretion on the pathogenesis of type 2 diabetes

Principal Advisor: A/Prof Frederic Gachon (IMB)

Associate Advisor: Dr Frederik Steyn (UQ School of Biomedical Sciences)

Associated with obesity and a sedentary lifestyle, T2D affects around 10% of the world’s population, mainly associated with morbid obesity. T2D starts with a pre-diabetic state characterized by an increased blood glucose level caused mainly by insulin resistance. As insulin overproduction occurs over a long period of time, insulin-producing pancreatic beta-cells lose their capacity to produce insulin, defining the beginning of T2D. Associated with obesity, insulin resistance is triggered by inflammation and fibrosis initiated by lipid accumulation. Metabolic diseases, including T2D, are characterized by a strong sex-specific difference of incidence defined by sex-dependent physiology and metabolism. This sex-specific difference is caused, in part, by the dimorphic secretion pattern of growth hormone (GH) between males and females. Interestingly, GH secretion is perturbed during T2D and has been associated with the development of the disease. However, in both human and animal models, changes in GH secretion protects against T2D, even in obese individuals. Therefore, we hypothesize that modulation of GH secretion pattern could be a protective response of the organism to counteract the development of T2D. The goal of this project is to test this hypothesis, opening new avenues for the treatment of T2D using time resolved sex-specific administration of GH.

Inflammasome inhibitors in disease: Is there a therapeutic trade-off of compromised host defence?

Principal Advisor: Prof Kate Schroder (IMB)

Associate Advisor: Dr Sabrina Sofia Burgener (IMB); Prof Avril Robertson

Inflammasome inhibitors offer tremendous promise as new disease-modifying therapeutics. Inflammasomes are signalling platforms with caspase-1 (CASP1) protease activity that induce potent inflammatory responses, including pathological inflammation and disease in many human conditions, such as chronic liver disease. Inflammasomes are thus exciting new drug targets, with inhibitors of one inflammasome (the NLRP3 inflammasome) entering Phase 2 clinical trials for the treatment of genetic auto-inflammatory disease and neurodegenerative diseases. Inhibitors that target multiple inflammasomes (e.g. CASP1 inhibitors) are currently under development for treating diseases driven by multiple inflammasomes (e.g. chronic liver disease). But the beneficial functions of these new therapeutics might come at a cost – a “trade-off” – of promoting patient susceptibility to infection. This is because inflammasomes also exert protective functions in host defence against microbes. For example, the NLRP3 inflammasome is essential for host defence against the clinically-important fungus Candida albicans limiting fungal dissemination and reducing disease, while in immunocompromised patients, C. albicans causes severe and life-threatening infections.

This project seeks to understand whether the future clinical use of inflammasome inhibitors for inflammatory disease treatment may come with the therapeutic trade-off of compromised host defence against C. albicans .

Introduction of VR and other technologies in ICU and patient outcomes

Associate Advisors: TBC

To study the feasibility, safety, and effectiveness of introduction of various technologies (including VR) and ability of patients to exercise, and impact on patient outcomes.

Investigating the importance of blood flow pattern for advanced life support

Associate Advisor: Professor John Fraser ( [email protected] )

Increasing number of patients with critical cardiac-respiratory failure is supported by advanced life support. Yet, certain conditions have failed to see any improvement in patient outcomes. The PhD fellow will work with industry leader to examine and develop the next generation advanced life support. Our previous study demonstrated superiority of pulsatile blood flow in supporting patients with cardiogenic shock. This PhD will focus on further understanding the underlying physiological and biological impact of blood flow pattern.

Investigating the molecular basis of motor neurone disease

Principal Advisor: Dr Fleur Garton (IMB)

Associate Advisor: Dr Adam Walker (QBI); Dr Allan McRae (IMB)

Motor neuron disease (MND) is a devastating disease for those affected and their family. It is an adult-onset, neurodegenerative disorder that progressively leads to paralysis and death. For most individuals with MND, diagnosis comes as a surprise, with no family history. The estimated genetic contribution to disease is significant and genome-wide association studies (GWAS) are now identifying these. The causal gene/mechanism is not known and further analyses must be carried out.

This project aims to identify molecular mechanisms contributing to MND to help support the path to translation. It will harness the in-house, Sporadic ALS Australia Systems Genomics Consortium (SALSA-SGC) platform. The current cohort, N~400 cases and N~200 controls is larger than existing datasets and has a rich set of matched data both genomic and clinical. Samples will be run for ‘omics analyses including DNA methylation and RNA-seq. Profiling expression with genomic and clinical data is expected to help identify lead disease mechanisms. Any new finding can be modelled in-vitro or in-vivo using cell or animal models. There is no effective treatment for MND and this project will help drive progress in unlocking molecular variations that contribute to the disease.

Lipid droplets and immune defence

Principal Advisor: Dr Harriet Lo ( [email protected] )

Associate Advisor: Dr Tom Hall ( [email protected] )

We recently discovered a novel process whereby eukaryotic cells are able to kill invading pathogens using lipid droplets. This project will use cell-based infection models and live imaging in zebrafish to identify and characterise the proteins involved.

Microenvironmental regulation of Melanoma Brain Metastasis

Principal Advisor: Dr Melanie White (IMB)

Associate Advisor: Dr Samantha Stehbens (AIBN); Prof Alan Rowan (AIBN)

Despite significant progress by scientists and clinicians, melanoma is often fatal due to rapid spread throughout the body, especially to the brain. The brain is vastly different to other tissues, and melanoma is particularly efficient at travelling to the brain and surviving in the new environment to establish disease there. Clinically, it is difficult to stop melanoma spreading to the brain and once it is there, it is complicated to treat. This is because melanoma in the brain is distinct due to the differences in the tissue structure and types of cells surrounding the tumour. This project will seek to develop novel integrative cancer models including cell biology and quail embryo xenograft models, to understand how melanoma survives in the brain microenvironment. By understanding crosstalk, we aim to identify a novel mechanism to block transmission of signals from the tumour microenvironment- inhibiting melanoma proliferation, survival, and invasion. This project is cross-disciplinary integrating cell biology with neuroscience and vascular biology.

Mitochondrial transplantation to improve donor heart function

Principal Advisor: Dr Jacky Suen ( [email protected] )

Associate Advisor: Professor John Fraser ( [email protected] )

This project focuses on the use of mitochondria transplantation to improve the quality and function of donor heart, in order to reduce the risk of primary graft dysfunction, as well as improving utility of marginal donor heart. Currently up to 80% of hearts were discarded, partly due to existing conditions. This is becoming an increasing problem as Australian faces an aging population. The fellow will work closely with our collaborator at Harvard Medical School and initial funding awarded from the Heart Foundation.

Modelling human genetic variants for muscle and adipose phenotypes using the zebrafish

Principal Advisor: Dr Tom Hall ( [email protected] )

Associate Advisor: Dr Harriet Lo ( [email protected] )

The results of genetic testing in humans are often difficult to interpret. This project will use live imaging and CRISPR/Cas9 technology to introduce human variants into zebrafish and examine the effects on muscle and adipose tissue.

Modulating G protein-coupled receptors in chronic inflammatory diseases

Principal Advisor: Prof David Fairlie (IMB)

Associate Advisor: A/Prof David Vesey (ATH, UQ Faculty of Medicine and Department of Nephrology, Princess Alexandra Hospital); Dr James Lim (IMB)

G protein-coupled receptors (GPCRs) are membrane-spanning proteins expressed on the cell surface and they act as signalling mediators between chemicals and proteins outside cells and signalling networks inside cells, enabling transduction of chemical signals into diverse physiological responses. Some of these receptors are the targets for about a third of all known pharmaceuticals, yet most GPCRs have not yet been sufficiently studied to become validated drug targets. We have previously discovered a number of GPCRs that are important links between extracellular signalling networks and intracellular metabolic signalling networks that drive inflammation and inflammatory diseases. This project will investigate the signalling connections between cellular activation of GPCRs and immunometabolic outputs that drive mouse models of chronic inflammatory/fibrotic disease associated with the liver/kidney. Techniques to be applied include PCR, western blots, cell culture, CRISPR-Cas9, flow cytometry, fluorescence microscopy, ELISA, G protein and b-arrestin signalling, GPCR secondary messenger assays (Ca2+, cAMP, ERK, Rho, arrestins, etc) and administration of experimental drugs to mouse models of chronic disease, measurement of metabolic, inflammatory and disease markers in tissues and cells. The project will be aided by availability of unique small molecule GPCR modulators, developed by chemists in our team, as probes and experimental drugs for various diseases.

Multi-modal biosensors for cell polarity and migration

Principal Advisor: Prof Jennifer Stow (IMB)

Associate Advisor: Dr Nicholas Condon (IMB); Prof Halina Rubinsztein-Dunlop (UQ School of Mathematics and Physics)

Epithelial cells and neurons are permanently polarised in order to perform directional transcytosis, endocytosis and secretion of many substances. This polarity is essential for allowing epithelial cells to act as selective barriers and for neurotransmission in neuronal networks. Many other cell types become transiently polarised, for instance while they are migrating, when they reorient to have a front and back. Measuring cell polarity is important for understanding both how cells and tissues normally function and the loss of function associated with genetic diseases, cancer, infection and inflammatory disease. This PhD project will create cellular models for measuring polarity and assessing loss of polarity after gene deletions. We will develop a suite of bifunctional, genetically-encoded biosensors as biological and biophysical detectors to measure polarised membrane domains in living cells. Model epithelial cells and neurons expressing these biosensors will be established as 3D organoids or in migration chambers and used to define polarity and to explore loss of polarity.

Novel pathways of stress signalling in cancer

Principal Advisor: Prof Rob Parton (IMB)

Associate Advisor: Dr Alan Rowan (AIBN); A/Prof Alpha Yap (IMB)

Caveolae, abundant cell surface organelles, have been extensively linked to chronic disease. Changes in the major proteins of caveolae have been linked to numerous cancers including breast cancer, pancreatic cancer, melanoma, thyroid cancer, gastric cancer, and colorectal cancer. In addition, caveolar proteins are dramatically upregulated in cells treated with chemo-therapeutics and their loss sensitises cells to toxic agents. Understanding the role of caveolae in cancer susceptibility and progression (to invasion and metastasis) requires a complete understanding of how caveolae, both in the cancer cell and the cancer cell environment, respond to intrinsic risk factors and to external stress.

This project will build on our findings that caveolae can sense mechanical and environmental stress. It will test the hypothesis that caveolae can protect cells against mechanical forces by activating signalling pathways from the cell surface to the nucleus and that loss of this pathway can promote DNA damage leading to cancer progression. It will employ novel systems in which defined mechanical stimuli can be combined with genetically-modified cells and state-of-the-art microscopic methods. This will define the role of caveolae in both the host cells, and in the neighbouring cellular environment, and determine the contribution of caveolar dysfunction to cancer progression.

Sleep & Circadian Rhythms in ICU

To study the quality and quantity of sleep for patients admitted to ICU. Also, to validate various proposed new methodologies to objectively evaluate sleep against current gold standard polysomnography. Finally, to evaluate the effect of an improved ICU bedspace environment on patient outcomes.

Targeting macrophage-mediated chronic inflammation

Principal Advisor: Prof Matt Sweet (IMB)

Associate Advisor: Prof Michael Yu (AIBN)

Macrophages are key cellular mediators of innate immunity. These danger-sensing cells are present in all tissues of the body, providing frontline defence against infection and initiating, coordinating, and resolving inflammation to maintain homeostasis. Dysregulated macrophage activation drives pathology in numerous inflammation-associated chronic diseases, for example chronic liver disease, inflammatory bowel disease, rheumatoid arthritis, atherosclerosis and cancers. Emerging technologies, including nanoparticle-mediated delivery of mRNAs and small molecules, provide exciting new opportunities to target otherwise "undruggable” intracellular molecules and pathways within macrophages. Such approaches hold great potential for manipulating macrophage functions to suppress inflammation-mediated chronic disease. This project will characterize and target specific pro-inflammatory signalling pathways in macrophages as proof-of-concept for intervention in chronic inflammatory diseases.

Understanding and preventing relapse of Inflammatory Bowel Disease

Principal Advisor: Prof Alpha Yap (IMB)

Associate Advisor: Dr Julie Davies (Mater, UQ)

The inflammatory bowel diseases, Crohn’s Disease and Ulcerative Colitis, are chronic diseases that display patterns of relapse and remission which contribute significantly to the burden that they carry. A key to reducing this burden, both for patients and the community, lies in being able to prolong how long patients stay in remission from active disease. Common approaches to maintain remission include immunosuppression and cytokine inhibitors, but these carry significant side effects and often eventually fail. In this project, we aim to investigate alternative ways to understand the mechanisms that lead to relapse, as a foundation to design new therapies. Specifically, our recent discoveries indicate that the mechanical properties of the bowel epithelium may play a critical role in relapse. Increased mechanical tension prevents the bowel epithelium from eliminating injured cells, thus increasing their capacity to provoke inflammation and disease relapse. We will pursue this by developing new clinically-applicable diagnostic tools to evaluate tissue mechanics and test how correcting mechanical properties can prevent disease relapse. Our goal is to support remission through approaches that can complement currently-available therapies.

Understanding blood vessel expansion and rupture using 3D models

Principal Advisor: Dr Emma Gordon (IMB)

Associate Advisor: Dr Mark Allenby (UQ School of Chemical Engineering)

Blood vessels are comprised of an ordered network of arteries, veins and capillaries, which supply oxygen and nutrients to all tissues of the body. Growth and expansion of the vascular system occurs during embryonic development, or in response to tissue injury or disease in the adult. As a result of their unique functions, vessels are subjected to distinct mechanical stresses that confer physical forces on cells that line the vessel wall, such as fluid shear stress, stretch and stiffness. In diseases of the vasculature, such as aortic and intracranial aneurysms, these physical forces become dysregulated, leading to changes in the shape of the vessel and eventually rupture. Using biofabrication technology and advanced imaging techniques, this project will use 3D printed models of the vasculature to study how changes in vessels occur at the molecular level in response to altered physical forces. These findings will allow us to understand how vessels may be manipulated to develop improved therapeutic strategies to prevent expansion and rupture.

Variants of neuronal ion channels that give rise to neurodevelopmental disorders

Principal Advisor: Dr Angelo Keramidas (IMB)

Associate Advisor: Prof Irina Vetter (IMB); A/Prof Victor Anggono (QBI)

Genetic variants of ion channels that mediate neuronal electrical communication (such as voltage-gated sodium channels and glutamate-gated synaptic receptors) can cause neurological disorders that include epilepsy, ataxia, neurodevelopmental delay and autism spectrum disorder. Understanding the molecular level deficits of an ion channel caused by a variant is essential to accurate molecular diagnosis and tailoring treatment options that correct variant-specific functional deficits. This personalised approach increases the efficacy of treatment, minimises side effects.

This project focussed on variants of voltage-gated sodium channels that are key generators of neuronal action potentials, and synaptic receptors such as GABA- and glutamate-gated ion channel receptors that mediate neuronal inhibition and excitation, respectively.

The project will combine high-resolution and high-throughput electrophysiology and pharmacology as well as ion channel protein synthesis and forward trafficking to understand the pathology of ion channel variants. Standard and new treatment options will be tested against each variant to optimise treatment that is tailored to each variant.

Together these approaches will enhance our understanding of the structure and function of neuronal ion channels and improve our understanding neurological disease mechanisms and treatments.

This project will involve a close collaboration between two groups across two institutes at UQ (IMB and QBI), offering students the opportunity for cross-disciplinary training in neuroscience research with the potential for therapeutic applications for patients.

Biosynthesis of circular antimicrobial peptides

Principal Advisor: Dr Conan Wang (IMB)

Associate Advisor: Prof David Craik (IMB); Prof Ian Henderson (IMB); Dr Thomas Durek (IMB)

Circular proteins are modified in a post-translational reaction that covalently joins their N- and C-termini. Deciphering the underlying biochemical reactions may lead to the development of new drugs that are more stable and potent and may provide new tools for protein and peptide engineering. Circular bacteriocins are a unique class of these biomolecules produced naturally by bacteria and have exhibited promising activities against a wide range of refractory pathogens in both the clinic and food industry. This project aims to reveal the secrets of how certain bacterial cells produce these proteins, how they protect themselves from the effects of these antimicrobials and how these molecules kill susceptible strains.

We encourage candidates with a strong background and interests in microbiology, biochemistry and/or molecular biology and who are interested in working in a diverse research environment, to apply. The host laboratory is embedded within the ARC Centre of Excellence for Innovations in Peptide and Protein Science, and therefore there are many opportunities to collaborate with scientists nationally and internationally. The project will involve whole-genome genetic manipulations, biochemistry, structural biology, biophysics and analytical chemistry. The project will lead to a better understanding of how some of nature’s most unique proteins are produced and could lead to new industry partnerships.

*Characterisation of blood-brain barrier nutrient transporters

Principal Advisor: Dr Rosemary Cater ( [email protected] )

Associate Advisor: Dr Anne Lagendijk ( [email protected] )

The blood-brain barrier (BBB) is a layer of tightly packed endothelial cells that separate the blood for the brain. The BBB has evolved to protect our brains from blood-borne neurotoxins and pathogens, but unfortunately, it also prevents the majority of potential neurotherapeutics from entering the brain. In fact, it has been estimated that ~98% of all small-molecule drugs are not able to cross the BBB. This creates a major bottleneck in the development of treatments for diseases such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, anxiety, and depression. The more we know about what can enter the brain, the better informed we will be for developing treatments for these diseases. Transporter proteins expressed at the BBB play a very important role in regulating the entrance of molecules in a highly specific manner. For example, the transporters FLVCR2 and MFSD2A allow for the uptake of choline and omega-3 fatty acids into the brain – both of which are essential nutrients that the brain requires in very large amounts. This project will utilise biochemical techniques and structural biology (cryo-EM) to further understand transport proteins at the BBB and how they transport specific molecules into the brain. This will provide critical insights that for the development of neurotherapeutics that can hijack these transporters to allow for entrance into the brain.

Deconstructing the genetic causes of disease to discover new drug targets

Principal Advisor: A/Prof Nathan Palpant (IMB)

Associate Advisor: Dr Andrew Mallett (IMB); Dr Sonia Shah (IMB), Dr Mikael Boden (UQ School of Chemistry and Molecular Biosciences)

Industry partnership opportunities: HAYA Therapeutics; Maze Therapeutics

Despite strong vetting for disease activity, only 10% of candidate new drugs in early-stage clinical trials are eventually approved. Previous studies have concluded that pipeline drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. This project will take advantage of increasing clinical disease data, rapid growth in GWAS datasets, drug approval databases, and innovative new computational methods developed by our team. The overall goal is to develop unsupervised computational approaches to understand what genetic models and data are most predictive of future drug successes. Underpinning this work, the project will build and implement computational and machine learning methods to dissect the relationships between genome regulation, disease susceptibility, genetic variation, and drug development. The project will not only reveal fundamental insights into genetic control of cell differentiation and function but also facilitate development of powerful unsupervised prediction methods that bridge genetic data with disease susceptibility and drug discovery. Students with background/expertise in computational bioinformatics and machine learning are ideal for this work. Informed by clinical, computational, and cell biological supervisory team, the project will have an opportunity to engage with diverse international companies through internships and collaborations to facilitate co-design of these methods for uptake in industry discovery and prediction pipelines.

Developing Models of Cancer Therapy-Induced Late Effects

Principal Advisor: Dr Hana Starbova (IMB)

Associate Advisor: Prof Irina Vetter (IMB; UQ School of Pharmacy); Dr Raelene Endersby (Telethon Kids Institute)

Treatments such as radiotherapy and chemotherapy for childhood and adult brain cancers save many lives. However, they also cause long-term debilitating adverse effects, also termed "late effects", such as pain, cognitive disabilities and sensory-motor neuropathies. Currently, no effective treatments are available, and brain cancer survivors are forced to live with long-term disabilities.

Animal models are important for the understanding of disease pathology and for preclinical testing of novel treatment strategies. However, currently there are no appropriate animal models available for the testing of late effects of cancer therapy.

To address this gap, this PhD project aims to develop in-vivo animal models of cancer therapy-induced late effects and to test the efficacy of novel treatment strategies. This project forms a foundation for future clinical studies.

Animal handling and behavioural assessments in rodents are vital for this project.

Developing new drugs targeting acid sensitive channels to treat ischemic heart disease

Principal Advisor: Prof Nathan Palpant (IMB)

Associate Advisor: Prof Jennifer Stow (IMB); Prof Brett Collins (IMB); A/Prof Markus Muttenthaler (IMB)

Industry partnership opportunities: Infensa Bioscience

This project focuses on strategies to prevent organ damage associated with ischemic injuries of the heart. There are no drugs that prevent organ damage caused by these injuries, which ultimately leads to chronic heart failure, making ischemic heart disease the leading cause of death worldwide. Globally, 1 in 5 people develop heart failure, with annual healthcare costs of $108 B. Our team has discovered a new class of molecules, acid sensitive ion channels, that mediate cell death responses in the heart during ischemic injuries like heart attacks. This project will study the function of acid sensing channels using cell and genetic approaches. We will use innovative new drug discovery platforms to find new peptides and small molecules that inhibit acid channel activity. Finally, the project will use disease modelling in stem cells and animals to evaluate the implications of manipulating these channels using genetic or pharmacological approaches to study the implications in models of myocardial infarction. The candidate will benefit from background/expertise in cell biology and biochemistry. Collectively, this project will deliver new insights, tools, and molecules that underpin a key area of unmet clinical need in cardiovascular disease. The project will be supervised by experts in drug discovery, cell biology, and cardiovascular biology and includes opportunities for internships with industry partners such as Infensa Bioscience, a new spinout company from IMB developing cardiovascular therapeutics for heart disease.

*Development of peptide-based blood-brain barrier shuttles

Principal Advisor: A/Prof Markus Muttenthaler ( [email protected] )

Associate Advisor: A/Prof. Johan Rosengren (SBMS, [email protected] )

The blood-brain barrier controls the transfer of substances between the blood and the brain, protecting us from toxic compounds while allowing the transfer of nutrients and other beneficial molecules. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. The project will involve cell culture, blood-brain barrier assays, proteomics, peptide chemistry, NMR structure determination, and molecular biology and pharmacology. The candidate should have a degree in biochemistry, pharmacology or cell biology, good hands-on laboratory skills and strong ambition and work ethics. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences.

Development of venom-derived blood-brain barrier shuttles

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences)

*Exploring Australian Microbes for Next-Generation Medicines through Soils for Science (S4S)

Principal Advisor: Dr Zeinab Khalil ( [email protected] )

Associate Advisor: Dr Angela Salim ( [email protected] ), Professor Rob Capon ( [email protected] ) and A/Prof Loic Yengo ( [email protected] )

Microbes have been a new promising source of modern medicines, including antibiotics (e.g. penicillin) and immunosuppressants (e.g. sirolimus) and well as agents to treat cancer (e.g. adriamycin) and cardiovascular (e.g. statins) disease, as well as many more. Recent advances in genomics offer the prospect of exciting new approaches to discovering the next generation of medicines hidden within the Australian microbiome.

This project will annotate the S4S microbe library to prioritize those that are genetically and chemically unique. These will be subjected to cultivation profiling, and fermentation, followed by chemical analysis to isolate, identify and evaluate new classes of chemical diversity.

The successful candidate will join a multi-disciplinary team where, supported by microbiological and genomic sciences, they will gain skills and experience in analytical, spectroscopic and medicinal chemistry – to inform and inspire the discovery of future medicines.

Applicants must have a strong background with outstanding grades in organic chemistry, and with an interest in learning multidisciplinary biosciences.

*Fine-tuning the application of peptide-based antimalarial drugs through understanding their mechanism of action

Principal Advisor: Dr Nicole Lawrence ( [email protected] )

Associate Advisor: Professor Denise Doolan ( [email protected] ) and Professor David Craik ( [email protected] )

Malaria is a disease caused by Plasmodium parasites. The disease kills half a million people every year and the parasites rapidly evolve resistance to new drugs. Developing new drugs with different ways of killing the parasites is important for staying ahead of the disease progression. We have developed peptide-based drugs that target red blood cells infected with malaria parasites. The peptides are safe and selective and are also less likely to result in the parasites developing drug resistance compared to existing small molecule drugs. We are seeking a motivated PhD student to join our discovery team and contribute valuable knowledge required for developing lead peptides into new treatments for malaria. The overall aims of the PhD project are:

1. Undertake genetic studies to understand how lead peptides affect malaria parasites at transcription and protein expression levels 2. Explore whether lead peptides have immune modulatory properties in animals 3. Identify combination treatment options by combining peptides with existing antimalarial drugs that have different mechanisms of killing parasites

Investigating the role and therapeutic potential of the oxytocin receptor in prostate cancer

Principal Advisor: A/Prof Markus Muttenthaler

Associate Advisor: A/Prof. Jyotsna Batra (QUT; [email protected] )

Prostate cancer is the second most frequent malignancy in men worldwide, causing over 375,000 deaths a year. When primary treatments fail, disease progression inevitably occurs, resulting in more aggressive subtypes with high mortality. This project focuses on the oxytocin/oxytocin receptor (OT/OTR) signalling system as a potential new drug target and biomarker to improve prostate cancer management and patient survival. Anticipated outcomes include a better understanding of OT/OTR’s role in prostate cancer and new therapeutic leads for an alternative treatment strategy.

The candidate should have a degree in biochemistry, pharmacology or cell biology, good hands-on laboratory skills, some bioinformatics skills (e.g., ability to implement statistical tests in R/Python and program scripts to automate analyses) and strong ambition and work ethics. The candidate will be involved in genetic/bioinformatic analysis, cancer cell signalling assays, chemical synthesis of OT ligands, GPCR pharmacology and characterisation of therapeutic leads in prostate cancer models.

Investigating the therapeutic potential of the trefoil factor family for treating gastrointestinal disorders.

Principal Advisor: A/Prof Markus Muttenthaler ( [email protected] )

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences; [email protected] )

Inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS) affect 10–15% of the population, having a substantial socio-economic impact on our society. The aetiology of these disorders remains unclear, and treatments focus primarily on symptoms rather than the underlying causes.

Our research group is pursuing innovative therapeutic strategies targeting gastrointestinal wound healing and protection to reduce and prevent such chronic gastrointestinal disorders. This project focuses on the trefoil factor family, an intriguing class of endogenous gut peptides and key regulators for gastrointestinal homeostasis and protection. The project will focus on the chemical synthesis of the individual members and molecular probe and therapeutic lead development to advance our understanding of their mechanism of action and explore the therapeutic potential of these peptides for treating or preventing gastrointestinal disorders.

The candidate should have a degree in chemistry, biochemistry, pharmacology or cell biology, good hands-on laboratory skills, and strong ambition and work ethics. The candidate will be involved in solid-phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, NMR, cell culture, wound healing assays, gut stability assays, cell signalling and receptor pharmacology.

*Mapping chemical diversity in Australian marine microbes

Associate Advisor: Dr Angela Salim ( [email protected] ), Professor Rob Capon ( [email protected] ) and Dr Mariusz Skwarczynski (SCMB)

There are multiple reasons why the discovery and development of new marine bioproducts is highly dependent on a quantitative understanding (mapping) of the chemical diversity intrinsic to different Australian marine biomass.

Firstly, the informed selection of marine biomass strains to support commercial production is greatly enhanced by knowledge of the yield, structures and diversity of small molecule and peptide bioactives – especially where these are the active agents critical to product properties (ie human health immunomodulatory, anti-infective, cardioprotective, neuroprotective and antioxidants; animal health antiparasitics; crop protection fungicides, herbicides and insecticides; livestock/crop productivity grow promoters; and/or new fine chemical pigments or flavouring agents).

Secondly, knowledge of chemical diversity and bioactives can significantly advance the design of optimal methods for production, harvest, handling, biorefining, biomanufacturer and product formulation, inclusive of quality control to monitor bioactive recovery, stability and content at each stage of the production cycle.

Thirdly, knowledge of chemical diversity can be used to improve the utilisation of biomass, and increase commercial returns, by identifying additional product classes from a single biomass. For example, analysis of biorefinery fractions after recovery of a primary marine bioproduct (ie omega-3-fatty acids or fucoidan) could reveal new product classes – with application inclusive of new functional foods and feeds, nutriceuticals, therapeutics, livestock and crop agrochemicals, and more.

This project seeks to develop advanced and optimised methods in UPLC-QTOF-MS/MS molecular networking, to rapidly, cost effectively, reproducibly and quantitatively map the small molecule and peptide chemical diversity of taxonomically and geographically diverse Australian marine microbes and microalgae, including fresh and processed biomass, biorefinery fractions and outputs, and formulated marine bioproducts – to advance the discovery and development of valuable new marine bioproducts.

*Medicinal chemistry strategies to remove bacterial biofilms associated with gastrointestinal disorders

Associate Advisor: Professor Mark Blaskovich ( [email protected] )

Gastrointestinal disorders such as irritable bowel disorders (IBS) and inflammatory bowel diseases (IBD) affect 10–15% of the population, reduce the quality of life of millions of individuals, and result in substantial socioeconomic costs. Recently, we revealed a high prevalence of macroscopically visible bacterial biofilms in the gastrointestinal tracts of IBD and IBS patients, linking these biofilms to a dysbiosis of the microbiome and the pathologies. Using patient-derived biofilm-producing bacterial strains, we established biofilm bioassays and identified leads capable of removing these biofilms.

This project pursues cutting-edge medicinal chemistry strategies to advance various lead molecules towards drug candidates and enhance their therapeutic window and biofilm-specificity. Techniques that will be acquired include: solid-phase peptide synthesis, organic chemistry, medicinal chemistry, high-performance liquid chromatography, mass spectrometry, proteomics, nuclear magnetic resonance spectroscopy, gut stability assays, and antimicrobial and biofilm assays.

The candidate should have a degree in chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and a desire to drive the project. The candidate will be involved in solid-phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, gut stability assays, and antimicrobial, antibiofilm and cytotoxicity assays.

Molecular mechanisms of jellyfish envenomation

Principal Advisor: Dr Andrew Walker (IMB)

Associate Advisor: A/Prof Nathan Palpant (IMB)

Jellyfish cause some of the most serious envenomation syndromes of all animals, responsible for >77 deaths in Australia to date and many more around the world. Two jellyfish of interest are the box jellyfish Chironex fleckeri, whose venom targets the heart to kill in as little as two minutes; and its much smaller relative the Irukandji jellyfish Carukia barnesi, envenomation by which causes a long-lasting and painful ordeal. Jellyfish also represent an ancient group of venomous animals with unique biology different from all other venomous animals. Despite this, little is known about jellyfish toxins, how they work, or how we might design therapeutics or novel treatments to ameliorate their effects. This project would involve combining state-of-the-art techniques to isolate and characterise jellyfish toxins, test them using a range of bioassays, and assess possible agents to protect from their harmful effects.

New chemical space as a source of new drug leads

Principal Advisor: Dr Zeinab Khalil (IMB)

Associate Advisor: Prof Ian Henderson (IMB); Prof Rob Capon (IMB)

To this end in 2020 we launched Soils for Science (S4S) as an Australia wide citizen science initiative, designed to engage the public, to collect 10's of thousands of soil samples from backyards across the nation, from which we will isolate 100's thousands of unique Australian microbes. This project will annotate the S4S microbe library to prioritize those that are genetically and chemically unique. These will be subjected to cultivation profiling, and fermentation, followed by chemical analysis to isolate, identify and evaluate new classes of chemical diversity.

Applicants must have a strong background with outstanding grades in organic chemistry, and with an interest in learning multidisciplinary biosciences.

*Targeting the oxytocin receptor for breast tumour reduction

Principal Advisor: A/Prof Markus Muttenthaler ( [email protected] )

Associate Advisor: A/Prof Loic Yengo ( [email protected] )

Over half a million women die from breast cancer annually (>3,000 in Australia), affecting one in eight women. It is therefore important to pursue new drug targets to improve therapy and patient survival. The oxytocin/oxytocin receptor (OT/OTR) signalling system plays a key role in childbirth, breastfeeding, mother-child bonding and social behaviour. It is also involved in breast cancer, where it modulates tumour growth, including subtypes such as triple-negative breast cancer that remain difficult to treat.

This project will investigate OT/OTR’s role in tumour growth and metastasis and assess its therapeutic potential in breast cancer management. It will focus on the OTR-specific tumour growth and metastasis pathways and on developing therapeutic leads derived from nature to reduce tumour growth. Anticipated outcomes include a better understanding of OT/OTR’s role in breast cancer and new therapeutic leads for an alternative treatment strategy.

The discovery and development of highly stable venom-derived peptide drug leads

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences)

Venoms comprise a highly complex cocktail of bioactive peptides evolved to paralyse prey and defend against predators. The homology of prey and predator receptors to human receptors renders many of these venom peptides also active on human receptors. Venoms have therefore become a rich source for new neurological tools and therapeutic leads with many translational opportunities.

This project covers the discovery, chemical synthesis, and structure-activity relationship studies of venom peptides, with a specific focus on gastrointestinal stability and drug targets in the gut. Venom peptides are known for their disulfide-rich frameworks supporting secondary structural motifs not only important for high potency and selectivity but also for improved metabolic stability. While primarily studied for their therapeutic potential as injectables, this project will break new ground by investigating evolutionarily optimised sequences and structures that can even withstand gastrointestinal digestions, thereby providing new insights for the development of oral peptide therapeutics targeting receptors within the gut. These therapeutic leads will have enormous potential for the prevention or treatment of gastrointestinal disorders or chronic abdominal pain.

The candidate should have a degree in synthetic chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and strong ambition and work ethics. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, NMR structure determination, CD studies, structure-activity relationship studies, gut stability assays, and receptor pharmacology.

The physiological role and therapeutic potential of gut peptides modulating appetite

Associate Advisor: Dr. Sebastian Furness (SBMS, [email protected] )

The advent of highly processed, calorie-rich foods in combination with increasingly sedentary lifestyles has seen a rapid rise in overweight and obesity. 60–80% of populations in developed countries are overweight or obese, and over three million deaths each year are attributed to a high body mass index. Obesity is also a risk factor for diabetes, hypertension, cardiovascular disease, kidney disease and cancer. This has a clear impact on life expectancy, with predictions that this generation will be the first to have a shorter life expectancy than the last. Despite this enormous socio-economic impact, treatment options are limited.

Our research groups are interested in the role of the gut peptides GLP-1 and CCK in regulating appetite and satiety. A subset of GLP-1 mimetics are already successful treatments for obesity; however, compliance is low as they are injectables. The project will focus on the development of orally active mimetics. The project will also develop molecular probes to facilitate the study of the GLP1 and CCK1 receptors in the context of appetite regulation across the gut-brain axis.

The candidate should have a degree in chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and a desire to drive the project. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, cell culture, gut stability assays, cell signalling and receptor pharmacology.

The therapeutic potential of the trefoil factor family in chronic gastrointestinal disorders

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: Prof Alpha Yap (IMB)

Inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS) affect 10–15% of the Western population, having a substantial socio-economic impact on our society. The aetiology of these disorders remains unclear, and treatments focus primarily on symptoms rather than the underlying causes.

The candidate should have a degree in chemistry, biochemistry, pharmacology or cell biology, good hands-on laboratory skills, and strong ambition and work ethics. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, NMR, cell culture, wound healing assays, gut stability assays, cell signalling and receptor pharmacology.

Towards the sustainable discovery and development of new antibiotics

Associate Advisor: Dr Angela Salim ( [email protected] ), Professor Rob Capon ( [email protected] ) and Professor Waldemar Vollmer ( [email protected] )

The worldwide emergence and relentless escalation of antibiotic drug resistance (i.e. methicillin-resistant Staphylococcus aureus) have demanded ongoing commitment over decades to discovering new antimicrobial weapons.1 Yet, even with the widespread acceptance of the need for new antibiotics in both the scientific community and the public at large, an urgent need for new approaches remains. Fortunately, microorganisms continue to produce their own wealth of structurally diverse and highly specialised metabolites, each with a remarkable range of biological activities that in themselves could present the next antibiotic breakthrough.

Microbial genomes are rich in silent biosynthetic gene clusters (BGCs), encoding for defensive agents (i.e. antibiotics) that fail to express in standard laboratory monoculture conditions, presumably due to the paucity of environmental cues. Nitric oxide (NO) is well known for its regulatory role in mammalian and plant biology, little is known about its role in regulating microbial silent BGCs. We revealed Nitric Oxide Mediated Transcriptional Activation (NOMETA) as a potentially cost-effective & rapid approach for an in situ (i.e. non-genome mining) approach to accessing the valuable chemistry encoded within microbial silent BGCs.

This project will deliver two key solutions to the major problem of AMR: (i) develop an innovative method that applies NO to activate the transcription of microbial silent BGCs to access new defensive agents capable of informing the development of new antibiotic classes, and (ii) apply new genomic and metabolomics data mining technologies for microbes identified in our Soils for Science citizen science program to identify additional antibiotics for future drug development.

Join our collaborative team as we explore the frontiers of analytical, spectroscopic, and medicinal chemistry, guided by the expertise of microbiological and genomic sciences. Together, we are on the verge of unveiling the mysteries of nature, paving the way for groundbreaking discoveries in the antibiotic drug discovery.

*Understanding the molecular structures of proteins involved in rare disease

Associate Advisor: Dr Brett Collins ( [email protected] )

Rare diseases are often caused by genetic mutations that disrupt protein function. In some cases, we already understand the three-dimensional structure and functional role of these proteins in healthy individuals. However, unfortunately, for some rare diseases, we lack this knowledge. This lack of information prevents us from understanding how mutations within the protein can lead to malfunction and disease onset, which in turn prevents us from understanding the disease and how to treat it. This project will employ biochemical techniques, structural biology (cryo-EM), and computational approaches to understand the normal 3D structure and role of proteins implicated in rare diseases. By elucidating these aspects, we will provide critical insights for the development of drugs to treat these rare diseases.

*Unveiling Potential Drug Candidates for Inflammatory Bowel Disease within the Rich Tapestry of the Australian Microbiome

rincipal Advisor: Dr Zeinab Khalil ( [email protected] )

Associate Advisor: Dr Angela Salim ( [email protected] ), Professor Rob Capon ( [email protected] ) and Dr Rabina Giri (Mater Health)

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, encompassing disorders like Crohn's disease and ulcerative colitis. With existing treatments often falling short, there's a growing need for innovative solutions.

In 2020, we initiated the Soils for Science (S4S) project, a nationwide citizen science endeavor collecting soil samples from backyards across Australia. Within this diverse microbial landscape, we seek answers to IBD.

Our mission involves annotating the S4S microbe library, prioritizing genetically and chemically unique microbes. Through cultivation profiling and fermentation, we aim to harness the untapped potential of these microbes for drug discovery. The ensuing chemical analysis will isolate, identify, and evaluate new compounds with the potential to revolutionize IBD treatment.

Join our multidisciplinary team and dive into the world of analytical, spectroscopic, and medicinal chemistry, guided by microbiological and genomic sciences. Together, we are poised to unlock nature's secrets and pave the way for groundbreaking treatments for Inflammatory Bowel Disease.

Using transposon sequencing to probe whole cell protein-protein interactions inside the bacterial cell

Principal Advisor: Dr Emily Goodall (IMB)

Associate Advisor: Prof Ben Hankerman (IMB); Prof Ian Henderson (IMB)

Friend or Foe, bacteria are powerhouses at the centre of many important biotechnological processes, but also the disease-causing agents of many infectious diseases. Understanding the fundamental processes of a bacterial cell is key to understanding (1) how to harness these organisms for biotechnological gain and (2) how to target them in the treatment of an infection. Using the model organism, Escherichia coli , we aim to develop a method for identifying protein-protein interactions in a high throughput format. The methodology developed in this project will enable total proteome screening and has implications for studying both fundamental cell physiology as well as the potential for studying protein-drug interactions in vivo. After development, the technology will be validated by screening for chemical inhibitors of protein-protein interactions.

Venom-derived drugs for targeting ion channels involved in genetic epilepsies

Principal Advisor: Prof Glenn King (IMB)

Associate Advisor: A/Prof Lata Vadlamudi (UQ Centre for Clinical Research)

There are more than 65 million people currently living with epilepsy, and more than 1/3 are resistant to anti-seizure medications (ASMs). For these latter patients, new efficacious ASMs are urgently required. This project will focus on development of biologic drugs for treatment of genetic epilepsies caused by aberrant expression of a voltage-gated ion channel. We are specifically interested in: (i) Dravet syndrome, which is caused by aberrant function of the voltage-gated sodium channel Nav1.1, and (ii) KCNH1 epilepsy, caused by gain-of-function mutations in the voltage-gated potassium channel Kv10.1, which was first described here at the Institute for Molecular Bioscience. This project brings together the expertise of the King lab in venoms-based peptide-drug discovery and development, and the clinical expertise of Prof. Vadlamudi in treatment of genetic epilepsies. Lead compounds will be isolated from arthropod venoms, the best known source of ion channel modulators. Prof. King’s lab has access to the largest collection of arthropod venoms in the world (>500 species). Lead compounds will be tested in brain organoids produced from patient-derived stem cells as well as in vivo rodent models of Dravet syndrome and KCNH1 epilepsy.

Venom-derived ion channel inhibitors as novel neuroprotective drugs for neurodegenerative diseases

Principal Advisor: Dr Fernanda C Cardoso (IMB)

Associate Advisor: Dr Jean Giacomotto (QBI/Griffith); Prof Glenn King (IMB)

Neurodegenerative diseases are caused by progressive loss of neurons, leading to dementia, motor dysfunction, paralysis, and death. Investigation of ion channels in central neurons unravelled clusters of voltage-gated ion channel subtypes playing a key pathological role in the pre-symptomatic stages of neurodegenerative diseases. Venoms are an exceptional source of peptides modulating ion channels with higher potency and selectivity than poorly efficacious drugs used in the treatment of neurodegeneration. This project involves systematically interrogating venoms using computational approaches, high throughput in vitro and in vivo screens, venomics and pharmacology to discover venom peptides that selectively modulate ion channels in central neurons and therefore have the potential to prevent central neurodegeneration. This is a multidisciplinary project in drug discovery utilizing venoms and other natural repertoires as main sources of bio-active molecules. PhD scholars will develop skills in computational biology, manual and automated whole-cell patch clamp electrophysiology, ex vivo tissue electrophysiology, in vivo screen in zebrafish, high performance liquid chromatography, mass spectrometry, recombinant expression, peptide synthesis, amongst other state-of-the-art methods and techniques. Students will author papers and be involved in writing and preparation of figures for research publications from their work.

Venom-derived peptides as novel analgesic leads

Principal Advisor: Prof Irina Vetter IMB)

Associate Advisor: Dr Richard Clark (UQ School of Biomedical Sciences)

Voltage-gated sodium channels are well-validated analgesic targets, with loss-of-function mutations leading to an inability to sense pain, but otherwise normal physiology and sensations. However, efforts to mirror these genetic phenotypes with small molecule inhibitors have highlighted that both selectivity over ion channel subtypes and mechanism of action are key considerations for the development of safe and effective analgesics.

This project will leverage the exquisite potency and selectivity of peptide sodium channel modulators from venoms for the rational development of novel, safe and effective molecules with analgesic activity.

Students will gain experience with peptide synthesis, patch-clamp electrophysiology, sensory neuron culture, microscopy and in vivo behavioural assays to tackle the global problem of unrelieved chronic pain with innovative molecules targeting peripheral sensory neuron function.

*Venom-derived peptides to study heart function and treat cardiovascular disease

Associate Advisor: A/Prof Nathan Palpant ( [email protected] )

Cardiovascular disease is the leading cause of death in the world. Although therapies have improved, mortality remains high, and 1 in 5 people develop heart failure, resulting in global annual healthcare costs of $108 billion. Innovative solutions are therefore required to develop new therapies for heart disease.

Venoms comprise a complex cocktail of bioactive peptides that target many human receptors and are therefore a rich source of new pharmacological tools and therapeutic leads. This project focuses on identifying and developing such new tools and leads with interesting functions on the human heart.

Techniques will include venom-heart-function screens, tissue culture, proteomics, chemical synthesis and structure-activity relationship studies. Identified compounds will support the study of heart function and might lead to innovations in the prevention or treatment of cardiovascular disorders.

The candidate should have a degree in biochemistry, pharmacology and/or cell biology, good hands-on laboratory skills, and strong ambition and work ethics.

Boosting innate immune defence to combat antibiotic-resistant bacterial infections

Principal Advisor: Prof Matt Sweet (IMB)

Associate Advisor: Prof Mark Schembri (IMB)

For bacterial pathogens to colonise the host and cause disease, they must first overcome frontline defence of the innate immune system. Innate immune cells such as macrophages engage a suite of direct antimicrobial responses to destroy engulfed bacteria, including free radical attack, lysosomal degradation, nutrient starvation, metal ion poisoning, and lipid droplet-mediated delivery of antimicrobial proteins. A detailed understanding of such pathways can provide opportunities to manipulate macrophage functions to combat antibiotic-resistant bacterial infections. This project will explore the regulation of specific macrophage antimicrobial responses, with the goal of manipulating the functions of these cells to combat infections caused by uropathogenic E. coli, a major cause of urinary tract infections and sepsis.

*Chemical embedding in artificial intelligence models

Principal Advisor: Dr Johannes Zuegg ( [email protected] )

The embedding of chemical structures for deep learning network is currently limited to a few approaches that fail to represent the chemical properties in an efficient and comprehensive way. Especially for large language models the embedding of chemical information is limited to methods containing few chemical properties, or associated biological activities in the case of bioactive chemicals. The project will explore and develop embedding methods that can enrich chemical and biological properties, using chemical relevant transformations to provide enriched descriptors. The project will explore their application in predictive and generative models, able to generate new chemical structures with a desired biological activity. The project has thereby access to the existing large of the Community for Open Antimicrobial Drug Discovery (CO-ADD), which has collected the structures and biological activity of over 500,000 chemicals.

*Developing ionobiotics for the targeted treatment of multi-drug resistant bacteria

Principal Advisor: Professor Mark Walker ( [email protected] )

Associate Advisor: Dr David De Oliveira ( [email protected] ) and Proessor Maree Smith (SBMS; [email protected] )

Antimicrobial resistance (AMR) is a growing source of morbidity, mortality, and economic and health-care costs. The innovative use of ionophores to break antibiotic resistance in clinically relevant multidrug-resistant bacteria has paved a therapeutic pathway to investigate ionophores as direct-acting antibiotics. By utilising a validated drug development program, this project will define the utility of these promising new compounds by exploring their mode of action, the range of pathogens that can be treated, and their drug pharmacology profiles during infection. Ionophores represent a NEW-CLASS of antibiotics with broad-spectrum activity against a wide range of antimicrobial-resistant bacterial species. Our overarching goal is to expand the repertoire of effective antibiotic therapies available for AMR associated infections.

Genetics of biofilms

Principal Advisor: Prof Mark Schembri ( [email protected] )

Associate Advisors: Dr Nhu Nguyen ( [email protected] ) and Dr Zack Lian (IMB; [email protected] )

Biofilms are surface-attached clusters of bacteria encased in an extracellular matrix and are significantly associated with increased antibiotic resistance. This project will apply molecular microbiology methods to understand the structure, function and regulation of biofilms produced by uropathogenic E. coli that cause urinary tract infections, and investigate new strategies to disrupt biofilms. The project will build skills in cutting edge genetic screens, molecular microbiology, genome sequencing, bioinformatics, microscopy, imaging and animal infection models. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

How antibiotic resistant bacteria cause urinary tract infection

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisor: Prof Matt Sweet (IMB)

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of ~175M cases. UTI is also a major precursor to sepsis, which affects ~50M people worldwide each year, with a mortality rate of 20-40% in developed countries. Uropathogenic E. coli (UPEC) is the major cause of UTI and a leading cause of sepsis. The last decade has seen an unprecedented rise in antibiotic resistance among UPEC, resulting in high rates of treatment failure and mounting pressure on healthcare systems. This project will explore how UPEC cause disease and become resistant to antibiotics, with a goal to identify new approaches to treat and prevent infection.

How bacteria cause severe life-threatening infections in infants

Associate Advisor: A/Prof Adam Irwin (UQ Centre for Clinical Research)

Neonatal meningitis is a devasting disease with high rates of mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis and the most common cause of meningitis in preterm neonates. Despite this, we have limited knowledge about the global epidemiology of E. coli that cause neonatal meningitis, genomic relationships between different strains, and mechanisms that enable E. coli to cause severe infection in new-born infants. This project will identify and characterise common genomic features of E. coli that cause neonatal meningitis, and employ molecular microbiology methods in conjunction with animal models to understand disease pathogenesis and antibiotic resistance. Our goal is to develop new diagnostic and therapeutic interventions to prevent this life-threatening disease.

How bacteria fortify their cell envelope under stress

Principal Advisor: Professor Waldemar Vollmer ( [email protected] )

Associate Advisor: Prof Mark Schembri ( [email protected] )

Gram-negative bacteria use some of their most abundant cellular proteins connect the outer membrane with the underlying cell wall (peptidoglycan) layer and this tight connection protects the cell from many toxic molecules and even antibiotics. However, most of the known peptidoglycan-interacting proteins are poorly characterised and we lack a comprehensive inventory of these proteins and their functions in key pathogens. In this project, the PhD student will develop novel proteomics approaches to identify all peptidoglycan-bound proteins in important Gram-negative pathogens, and then identify peptidoglycan-interacting proteins that fortify the cell envelope when bacteria encounter host defence factors and antibiotics. In addition to state-of-the art molecular biology and high-throughput microbiology screening techniques, the student will use cell biology and biochemical methodologies to gain understanding of the cellular roles of new cell envelope proteins identified. The student will benefit from working in an outstanding research environment and in research groups with a strong expertise in bacterial cell envelope biology and pathogenicity. The expected outcomes will be important to develop new strategies to fight infections caused by antibiotic resistant bacteria.

*How E. coli cause urinary tract infections

Principal Advisor: Professor Mark Schembri ( [email protected] )

Associate Advisors: Professor Matthew Sweet ( [email protected] )

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of approximately 400 million cases. UTI is also a major precursor to sepsis, which affects about 50 million people worldwide each year, with a mortality rate of 20-40% in developed countries. Uropathogenic E. coli (UPEC) is the major cause of UTI and a leading cause of sepsis, and associated with high rates of antibiotic resistance. This project will explore how UPEC cause disease, with a goal to identify new approaches to treat and prevent infection. Students with an interest in microbiology, bacterial pathogenesis, animal infection models and antibiotic resistance are encouraged to apply.

How does innate immune signalling combat influenza in birds?

Principal Advisor: Dr Larisa Labzin (IMB)

Associate Advisor: A/Prof Kirsty Short (UQ School of Chemistry and Molecular Biosciences)

Emerging viruses such as Highly Pathogenic Avian Influenza, HPAIV and SARS-CoV-2 can cause deadly outbreaks that decimate wild and domestic animal populations or cause global pandemics. . Some species, particularly bats and wild birds, can carry these viruses with minimal disease, meaning they can easily spread viruses between farms, states and even countries. The immune response is the best protection against viral infection, yet in susceptible species (such as chickens and pigs), immune overactivation may cause collateral tissue damage, driving disease pathology. This PhD project will study how the immune systems of different species recognise viral infections. This research will determine if viral reservoir species (such as ducks and bats) mount a specific kind of immune response that allows them to tolerate viruses, which is distinct to susceptible species (such as chickens and pigs). This project will utilise cell biology, imaging, molecular cloning, and virology to identify new ways to prevent pandemic virus outbreaks and protect vulnerable species.

Molecular Immunology of Malaria

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Prof Gabrielle Belz (Frazer Institute)

An opportunity exists for a PhD position in the molecular immunology of malaria. The focus of this project will be to apply cutting-edge technologies to understand the molecular basis of protective immunity to malaria. It will take advantage of controlled human infection models and as well as animal models to explore the mechanisms underlying protective immunity to malaria and immune responsiveness. Using a range of interdisciplinary approaches including immune profiling, transcriptomics, proteomics, and small molecule characterization, the project aims to define the critical cells and signalling pathways required for protective immunity against malaria. It is anticipated that this research will have broad application to a wide range of infectious and chronic diseases, with important implications for vaccination.

Subject areas: Immunology, Molecular immunology, Systems biology, Vaccinology, Malaria Eligibility: Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements). Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; excellent computer, communication, and organisational skills are required.

Novel assays for antibiotic discovery

Principal Advisor: Prof Waldemar Vollmer (IMB)

Associate Advisor: Mr Alun Jones (IMB); Prof Rob Capon (IMB)

The PhD project addresses the global burden of Antimicrobial Drug Resistance (AMR) by developing new assays for antibiotic discovery. The bacterial cell wall is targeted by some of our best antibiotics (e.g., beta-lactams, glycopeptides) and remains an attractive target for antibiotic drug discovery. Our group investigates the molecular mechanisms underpinning cell wall synthesis during growth and division of a bacterial cell. We pioneered the development of biochemical assays to monitor the activities and interactions of essential enzymes required for the synthesis of peptidoglycan, identified the first activators of peptidoglycan synthases and deciphered the activation mechanism. The PGR student will be trained in a wide range of molecular biology, (analytical) biochemistry and bacterial cell biology techniques and use these to develop innovative assay for key peptidoglycan enzymes that built and remodel the cell wall in pathogenic bacteria. The PGR student will then use the new assays to screen compound libraries to identify inhibitors. Hit compounds will be characterised by cellular and biochemical techniques and assessed for their potential to be developed into new antibiotics.

PET Imaging of Bacterial Infections

Principal Advisor: A/Prof Mark Blaskovich (IMB)

Associate Advisor: Prof Kristofer Thurecht (UQ Centre for Advanced Imaging); Dr Anthony Verdosa (IMB)

Infections caused by drug resistant bacteria pose a significant threat to global human health, with predicted annual mortality of 10 million by 2050. Most research is focused on developing better therapies, but improving diagnosis could quickly have substantial impact by reducing unnecessary antibiotic use and enhancing therapeutic efficacy. There is no current clinical technology capable of specifically identifying bacterial infections by imaging the site of a bacterial infection. Suspected chronic infections, such as endocarditis and prosthetic joint infections, are particularly difficult to accurately diagnose without invasive techniques. A whole-body imaging diagnostic that could simultaneously determine whether an infection was present and rapidly pinpoint the site of the infection, then monitor the efficacy of subsequent treatment, would directly inform targeted treatment, leading to substantial health and economic benefits. This project will extend our current research on fluorescent tracers that bind to the surface of bacteria with high specificity and selectivity. We will replace the fluorophore component of these tracers with radioisotope chelating ligands, creating new constructs suitable for positron emission tomography (PET) whole body imaging. These tracers will be tested both in vitro and in mice to demonstrate specific PET imaging of bacterial infections.

Systems immunology and multi-omics approaches to understand protective immunity to human malaria

Associate Advisor: Dr Carla Prioetti (IMB); A/Prof Jessica Mar (AIBN)

This PhD project aims to develop and apply computational approaches that integrate systems biology and molecular immunology to understand host-pathogen immunity and predict immune control of malaria. The project will utilise systems-based immunology and multi-omics approaches to profile the host immune response in controlled infection models of malaria at molecular, cellular, transcriptome and proteome-wide scale.

The overall aim will be to develop and apply omics-based technologies and computational tools, including network theory and machine learning, to integrate multiple high-dimensional datasets and reveal novel insights into host-pathogen immunity and predict immune responsiveness and parasite control. Modelling of large-scale existing datasets, including those generated by single-cell RNA-sequencing technologies, may also be a feature of this project. The opportunity to identify new knowledge and integrate this with experimental data produced by our laboratory will be instrumental to extending the impact of these bioinformatics analyses. This project will provide an opportunity to be at the forefront in cutting-edge technologies and advances in computational analysis of integrated high-dimensional omic data.

Eligibility:

Entry: BSc Honours Class I (or equivalent via outstanding record of professional or research achievements) Experience/Background: Experience with programming languages, mathematics, statistics and/or background in immunology and molecular sciences, with an interest in integrating the fields of immunology and bioinformatics.

Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged.

Targeting the membrane steps in bacterial cell wall synthesis for antibiotic drug discovery

Principal Advisor: Prof Waldemar Vollmer (IMB)

Associate Advisor: Mr Alun Jones (IMB); Prof Rob Capon (IMB)

There is an urgent need to develop new antibiotics to address the global challenge of antimicrobial drug resistance (AMR). The membrane steps in bacterial cell wall biogenesis include verified targets for antibiotics (e.g. daptomycin, teixobactin) which cause death and lysis of a bacterial cell. We study the key essential steps of cell wall synthesis at the cell membrane, including the synthesis of lipid-linked precursor, the polymerisation of the cell wall and the recycling of the carrier lipid. The PGR student will receive extensive training in molecular biology, biochemistry and mass spectrometry techniques and develop new assays to measure the activities of membrane-bound cell wall enzymes. The PGR student will then use the new assays in proof-of-principle studies to screen for new inhibitors. The student will characterise the activity of hit molecules by bacterial cell biology techniques and assess their potential to be developed into new antibiotics.

References: 1. Egan et al. 2020. Regulation of peptidoglycan synthesis and remodelling. Nature Reviews Microbiology 18, 446–460. 2. Oluwole et al. 2022. Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients. Nature Communications 13:2278.

The application of metagenomics to clinical microbiology and infection control

Principal Advisor: Dr Brian Forde ( [email protected] )

Associate Advisors: Dr Patrick Harris (UQCCR, [email protected] ), Dr Kym Lowry (UQCCR, [email protected] )

Hospital-acquired infections (HAIs) present significant healthcare challenges globally, affecting patients in both developed and developing nations. In Australia alone, over 165,000 patients suffer from HAIs annually, with antimicrobial resistance (AMR) compounding the issue by limiting treatment options and worsening patient outcomes. Prospective whole-genome sequencing (WGS) has emerged as an optimal approach for rapidly identifying transmission of multi-drug resistant (MDR) bacteria. However, current surveillance methods primarily rely on culture-based isolation of specific pathogens, followed by detailed genomics characterisation of individuals, which is labour-intensive, prone to selection bias, and fails to provide insights into community dynamics and interactions between patients and the hospital environment. This project aims to pioneer an alternative approach: prospective metagenomic surveillance. By leveraging high-throughput metagenomics, this project seeks to profile overall community structure, characterise community dynamics, and identify and control pathogen transmission in clinical settings. The research will involve developing new workflows and pipelines to integrate metagenomic surveillance into routine clinical practice, thereby enhancing infection control strategies and patient care

Understanding antibiotic resistance

Associate Advisor: Dr Brian Forde ( [email protected] ), Dr Patrick Harris (UQCCR; [email protected] ), Dr Minh-Duy Phan (IMB; [email protected] )

Antimicrobial resistance (AMR) is a major threat to global human health. In 2019 alone, there were an estimated 4.95 million deaths associated with bacterial AMR, with uropathogenic E. coli (UPEC) a leading pathogen associated with urinary tract infections, sepsis and high rates of antibiotic resistance. This project will use cutting edge genetic screens, molecular microbiology, genome sequencing and bioinformatics to understand how plasmids contribute to the spread of antibiotic resistance in UPEC. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

Understanding the link between EBV and Multiple Sclerosis

Associate Advisor: Dr Carla Prioetti (IMB)

An opportunity exists for a PhD position in molecular immunology, where cutting-edge technologies will be applied to understand the molecular basis of the link between EBV and Multiple Sclerosis. Epstein-Barr virus (EBV) is the top identified causative agent of Multiple Sclerosis , but how this occurs is not known. This project aims to apply an innovative approach using proteome-wide screening of EBV to identify the subset of EBV proteins from the complete EBV proteome that triggers MS. It will compare responses in individuals with different stages of MS and apply sophisticated computational analytics to identify specific EBV proteins that predict MS disease. This EBV signature of MS could be translated into a clinic-friendly point-of-care test. If successful, this project could revolutionize the diagnosis and management of MS, providing patients with a quicker and more accurate diagnosis and enhanced quality of life.

Eligibility: Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements) Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; excellent computer, communication, and organisational skills are required.

Understanding the role of lipids in inflammation and immune clearance of pathogens

Principal Advisor: Dr Jessica Rooke (IMB)

Associate Advisor: Prof Ian Henderson (IMB); Prof Matt Sweet (IMB)

Salmonella enterica is a broad host range pathogen that is distributed globally. Worryingly, S. enterica strains are becoming increasingly resistant to routinely used antibiotics, leading to the World Health Organisation classifying S. enterica as a high priority pathogen for which alternative treatments are desperately needed. By understanding how Salmonella infects a host, novel therapies and vaccines can be designed to prevent disease. Recent evidence suggests that pathogen-lipid interactions are important for pathogens to survive in the host and that Salmonella has a unique, conserved lipase that is essential for these interactions. This project aims to establish the molecular mechanism by which Salmonella interacts with host lipids to enable evasion and manipulation of host immune responses. These investigations will provide novel insights into fundamental Salmonella biology and aid in the development of more effective strategies to treat Salmonella infections, such as novel drug targets and/or novel vaccine candidates.

Vaccine Engineering

An opportunity exists for a PhD position in vaccine engineering. Vaccines are one of the most effective health care interventions but remain a challenge for many diseases, and in particular intracellular pathogens such as malaria where T cell responses are particularly desirable. We have been exploring novel approaches to rationally design an effective vaccine against challenging disease targets. By taking advantage of recent advances in genomic sequencing, proteomics, transcriptional profiling, and molecular immunology, we have discovered unique targets of T cell responses or antibody response. This project will test these antigens as vaccine candidates by assessing immunogenicity, protective capacity and biological function using different vaccine platforms. By designing an effective vaccine from genomic data, this project is expected to result in significance advances in vaccinology as well as immunology, with important public health outcomes.

Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements) Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; e xcellent computer, communication, and organisational skills are required.

Gender matters: Using genomic data to understand sex-specific risk in heart disease

Principal Advisor: Dr Sonia Shah (IMB)

Associate Advisor: Prof Gita Mishra (UQ School of Public Health)

The 2019 Women and Heart Disease forum highlighted clear disparities in CVD outcomes between males and females. The report (Arnott et al 2019 Heart, Lung and Circulation), highlighted a need to increase our understanding of sex-specific pathophysiology driving susceptibility to common diseases, and identification of sex-specific risk factors to improve early detection and prevention of CVD in women. Until recently, sex-specific research was underpowered and most studies on heart disease included a much smaller number of female participants. But this is beginning to change with the availability of large biobank data. This project will require statistical analysis of very large datasets with health records linked to genomic data to address these gaps in our understanding of heart disease in women. This includes data from the UK Biobank cohort in ~500,000 individuals (54% women) and data from the Australian Women’s Longitudinal Study (led by Prof Gita Mishra), a study looking at the factors contributing to the health and wellbeing of over 57,000 Australian women, and is the largest, longest-running project of its kind ever conducted in Australia. This project will lead to a better understanding of sex-specific risk factors for CVD, which will inform better CVD prevention strategies in women.

Genomics of Caveolae Disease

Principal Advisor: Dr Allan McRae (IMB)

Associate Advisor: Prof Robert Parton (IMB)

Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. Loss or mutation of genes involved in caveolae have shown to cause disease including lipodystrophy and pulmonary arterial hypertension. This project will ustilise publicly available genomic data to further explore the role of genetic variation in caveole genes in disease.

Harnessing biobank information to understand Motor Neuron Disease

Associate Advisor: Dr Fleur Garton (IMB), A/Prof Robert Henderson (UQ Centre for Clinical Research)

Motor neuron disease results in the degeneration of the motor neurons leading to paralysis and death. There is limited knowledge on the underlying causes and no treatment can significantly change the fatal course of the disease. Slowing the discovery process has been the limited, clinic-based sample sizes. At least three large international biobank datasets, with matched genotype and phenotype data are now available and more are anticipated. The large sample provides a powerful opportunity to investigate this complex disease. Our group has expertise in harnessing large datasets such as the UK Biobank to answer questions about complex traits and diseases. This project will aim to integrate multiple international biobank datasets to better understand the disease and avenues for treatment.

Leveraging high-throughput genetic screens to evolve the power of algae in biotechnology

Principal Advisor: Prof Ben Hankamer

Associate Advisor: Prof Ian Henderson

Algae cells have evolved over ~3 billion years of natural selection to yield a diverse array of highly efficient, self-assembling, light-responsive membranes. These act as Nature’s solar interfaces, via which plants tap into the power of the sun. These interfaces contain nano-machinery to drive the photosynthetic light reactions which convert light from the sun into food, fuel, and atmospheric oxygen to support life on Earth. However, microalgae can be used to produce foods/nutraceuticals, vaccines, peptide therapeutics, novel antibiotics, fuel, and bioremediation. While much successful work has been done to improve the use of algae, the genetics of the various species are not well understood. Here we will deploy a high through put genetic approach to identify essential and conditionally-essential genes in algae providing insight into the fundamental biology of these organisms. We will leverage this approach to forcibly evolve algae and improve recombinant protein production.

Parsing the genome into functional units to understand the genetic basis of cell identity and function

Principal Advisor: Associate Professor Nathan Palpant ( [email protected] )

Associate Advisors: Dr Woo Jun Shim ( [email protected] ), Dr Sonia Shah ( [email protected] ), Dr Bastien Llamas (University of Adelaide)

The billions of bases in the genome are shared among all cell types and tissues in the body. Understanding how regions of the genome control the diverse functions of cells is fundamental to understanding evolution, development, and disease. We recently identified approaches to define diverse biologically constrained regions of the genome that appear to control very specific cellular functions. This project will evaluate how these biologically constrained regions of the genome have influenced evolutionary processes, evaluate their regulatory basis in controlling the identity and function of cells, and analyse the promiscuity of cross-talk between different biologically constrained regions. The project will also study how these genomic regions impact disease mechanisms by evaluating how disease-associated variants in different regions influence survival of patients with cancer and assessing whether these regions are associated with identifying causal disease variants in human complex trait data. The project will involve significant collaborative work with industry partners and researchers across Australia with the goal of providing critical insights into fundamental mechanisms of genome regulation.

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Proietti (IMB); Dr Jessica Mar (AIBN)

We invite applications for a PhD position focused on identifying human host factors that predict immune control of malaria. The project will utilise systems-based immunology and multi-omics approaches to profile the host immune response in controlled infection models of malaria at molecular, cellular, transcriptome and proteome-wide scale. The overall aim will be to develop and apply computational approaches, including network theory and machine learning, which integrate systems biology and molecular immunology to understand host-pathogen immunity and predict immune responsiveness and parasite control. Modelling of largescale existing datasets, including those generated by single cell RNA-sequencing technologies, may also be a feature of this project. The opportunity to identify new knowledge and integrate this with experimental data produced by our laboratory will be instrumental to extending the impact of these bioinformatics analyses. This project will provide an opportunity to be involved in cutting-edge advances integrating diverse fields of high dimensional omic datasets to inform the development of vaccines, immunotherapies or diagnostic biomarkers.

Methodologies: Bioinformatics, Machine Learning, Immunology, Systems Immunology, Systems Biology, Genomics/Proteomics/Transcriptomics, Molecular and Cell Biology, Statistics

Eligibility: Entry: BSc Honours Class I (or equivalent via outstanding record of professional or research achievements) Experience/Background: Experience with programming languages, mathematics, statistics and/or background in immunology and molecular sciences, with an interest in integrating the fields of immunology and bioinformatics. Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged.

Understanding the genetic and phenotypic basis of rare disease variants

Associate Advisors: Dr Sonia Shah ( [email protected] ) and Dr Mikael Boden (SCMB)

Genome sequencing is a powerful tool for studying the biological basis of disease, yet out of millions of data points, finding the underlying cause of disease can be difficult. Current protocols for classifying variants from patient DNA data largely rely on prior knowledge about normal and abnormal gene variation contained in large public databases, known disease-causing gene panels, or identifying variants causing amino acid changes in proteins (which only comprise 2% of the genome). Despite these powerful approaches, studies indicate that classifying variants as pathogenic occurs in only a minority of cases and among variants reported in ClinVar, a public archive of relationships between human variation and phenotype, wherein a large proportion (37%) are classified as variants of unknown significance (VUS). This project aims to address this key gap in knowledge, involving work in computational and/or cell biology studies, depending on the student skills and interests. For computational studies, this project aims to develop methods that integrate predictive, genome-wide identifiers of pathogenicity. We will use machine learning to build non-linear prediction methods that outperform individual prediction tools in identifying genetic causes of disease and accelerating clinical diagnosis of genetic diseases. For cell biology studies, we aim to use clinical genetics data (from the Australian Functional Genomics Network) to determine pathogenicity of variants from patients with inherited cardiovascular diseases. The approaches will include: 1) cell modelling with human pluripotent stem cells (hPSCs), a disease-agnostic and scalable platform for high-throughput hPSC variant screening. To study variants in genes such as transcription factors that are known to cause genetic diseases, we will use molecular phenotyping by genome-wide proximity labelling with DNA adenine methyltransferase (DamID) to study how disease-causing variants alter regulatory control of the genome. Collectively, this aim implements computational predictions with disease modelling as an efficient, scalable, and disease agnostic pipeline to increase the diagnostic rate of unresolved cases.

Using genetic adaptation to high altitude to discover mechanisms regulating acute responses to ischemia

Associate Advisors: Professor Glenn King ( [email protected] ), Dr Sonia Shah ( [email protected] ) and Dr Toby Passioura (University of Sydey)

Human populations living in high-altitude hypoxic environments have shown generational gene adaptations compared to lowland cohorts. These extreme stresses result in adaptive changes in the genome to maintain cell viability and function. We hypothesise that genes adapted to high altitude provide a unique approach for discovering novel mechanisms to protect organs from acute ischemic stresses like heart attacks. My laboratory is studying the genetics of lowland versus highland populations in China and Central America and using human pluripotent stem cells (hiPSCs) to study genes selected for high-altitude survival. Preliminary single-cell RNA-seq analysis of differentiated European vs. Han Chinese iPSCs revealed a unique gene expression signature for hypoxia pathways shared by the Han Chinese iPSCs with high altitude-associated haplotypes. We have also identified the gene encoding TMEM206, an acid-sensing ion channel, as a candidate “high-altitude gene”. Genetic knockout of TMEM206 reduces cardiomyocyte sensitivity to ischemia. These data and cell tools are a rich resource for discovering genes under adaptive pressure that could in turn reveal mechanisms and drug targets for protecting the heart against acute injury. This project will use iPSCs selected by known high-altitude haplotypes and compared using in vitro ischemia assays to measure cardiomyocyte cell death. We will analyse haplotype differences in differentiated cardiomyocytes by RNA-seq to identify gene expression programs associated with high altitude-adapted genotypes. We will then use the Broad Institute Connectivity MAP, which links drug perturbations to gene expression changes, to identify novel drugs that induce a “high altitude” gene expression profile in cardiomyocytes. Candidate drugs will be tested in wildtype cells (lacking the high-altitude haplotypes) to assess efficacy in reducing cell death during acute ischemic stress. Using our CRISPR gene methods, we will also knockout candidate “high-altitude genes” identified from statistical genetic studies and assay them using in vitro acidosis/ischemia models. For genes such as TMEM206 that show a role in mediating cardiomyocyte cell death, we will work with associate supervisors Glenn King (UQ) and Toby Passioura (U Sydney) in using the RaPID screen to discover cyclic peptides that inhibit stress-sensitive ion channels.

Earmarked PhD Projects

Earmarked PhD Projects are projects that are aligned to recently awarded research grants. They are accompanied by a UQ Earmarked Scholarship which is funded by the Australian Government and offered to support candidates with their living costs and tuition fees. Applications are now open to Domestic and International (onshore and offshore) candidates. Please see project description to confirm the project's individual application deadline as it may vary.

When you are ready to apply, please contact the Principal Advisor via email ensuring the project title is in the subject line and your latest CV is attached. Once you have confirmation that they will endorse you for your chosen project, you may officially apply via the UQ Application Portal following the instructions listed on the UQ Earmarked Scholarship site. Sign up to alerts to be notified of any new Earmarked PhD projects as well as other PhD opportunities.

Characterising a specific regulator of venous vessel integrity

Principal Advisor: Dr Anne Lagendijk (IMB)

Associate Advisor: Dr Emma Gordon (IMB)

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Our blood vasculature forms a protective barrier between the blood and surrounding tissues. Blood vessels are kept intact by building strong connections between cells that line the blood vessel wall. These connections are established by adhesion proteins. We have uncovered that adrenomedullin peptides can control adhesion in veins but not arteries. This project aims to understand how adrenomedullin controls venous adhesion so specifically and if this is conserved between species. We will examine this using uniquely suitable mammalian models. The project aims to improve our understanding on how to strengthen vessels and holds the potential to enhance tissue engineering and will expand the scope of Australian research.

*Qualifies for an Earmarked Scholarship .

Early warning mechanisms for epithelial tissue self-protection

Principal Advisor: Prof Alpha Yap (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This project aims to discover how epithelial tissues in the body protect themselves against cell injury and cancerous transformation through the early detection and elimination of abnormal cells. Epithelia are found in major organs, such as the lung, breast and gastrointestinal tract - tissues that are common sources of major diseases, such as inflammation and cancer. The Yap group has pioneered work to understand how mechanical forces are detected as early warnings of cellular dysfunction in epithelia. Conversely, we have found that abnormal tissue mechanics may increase the susceptibility of epithelial tissues to disease. We aim to understand how mechanical signals are detected, how they may be disturbed, and whether correcting mechanics can improve disease outcomes. We work at the interface between experimental biology and theoretical physics. So, projects can be tailored to student's interests, but will give experience in experimental cell biology and physical theory.

*Qualifies for an Earmarked Scholarship .

Host-Microbe Interactions and the circadian clock in Liver Disease

Principal Advisor: Dr Benjamin Weger (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2026, which means you must apply no later than 30 September, 2025.

Non-alcoholic fatty liver disease (NAFLD) is a major global health problem and refers to a spectrum of liver conditions including simple steatosis, non-alcoholic steatohepatitis and fibrosis. NAFLD affects at least 25% of adults in developed nations and is a leading cause of cirrhosis and hepatocellular carcinoma, but current treatment options remain limited.

Increasing evidence points to a crucial role of gut microbiota in the pathophysiology of NAFLD, yet the underlying mechanisms remain scarcely understood. This PhD project is based on our findings that microbiota modulates growth hormone (GH) secretion of the host (microbiota-GH axis) to regulate diurnal/circadian liver physiology in a sex-dependent manner.

The study will explore the role of an altered microbiota-GH axis in NAFLD progression and will test whether its targeted modulation may provide a new way for treating NAFLD. This project involves a multi-omics approach and combines innovative cell culture and pre-clinical models of NAFLD. Students with an interest in liver physiology and/or the circadian clock are encouraged to apply.

How epithelial tissues detect and respond to cell death and injury

Principal Advisor: Professor Alpha Yap (IMB)

Associate Advisor: TBC

Two PhD projects are available as part of Professor Yap’s ARC Laureate Program which commences in 2024. This prestigious 5-year program aims to understand how cells communicate with one another by mechanical force to detect injury in epithelial tissues such as the gastrointestinal tract and embryonic skin. We apply physical and cell biological approaches to understand how those mechanical forces are generated and detected for tissue health and repair. We use innovative approaches from different disciplines, including live-cell microscopy and genetic manipulation in zebrafish embryos; experimental tools and theory from physics that provide new ways to understand the biological phenomena; and testing how failure of mechanical communication may allow injury to disrupt tissue integrity. Individual projects will be designed that emphasize different aspects within this overall program, tailored for the specific interests of students, which can range from biology to biological physics. Independent of the specific focus of an individual project, the interdisciplinary range of this Laureate Program provides an exciting opportunity for students to train across biological and physical disciplines, to enhance their capacity and versatility for the future.

Research Environment

These projects will be supported by the world-class resources of the IMB and the network of national and international experts who are collaborating with Professor Yap’s ARC Laureate Program. Depending on the specific requirements of each project, students have the opportunity to learn cutting-edge experimental approaches, such as biophysical techniques to analyse tissue mechanics and the use of organoids and zebrafish embryos to model cell injury and tissue responses. This project is part of a program that provide a rich, interdisciplinary network for their training. Local collaborators bring experience in cell biology (Prof. Rob Parton, Dr. Samantha Stehbens), zebrafish models (Dr Anne Lagendijk),inflammation (Professors Kate Schroder and Matt Sweet) and gastrointestinal function (Professor Jake Begun, MMRI-UQ); while national and international collaborators bring expertise in mechanobiology (e.g. Richard Morris, UNSW; Virgile Viasnoff, Nat Uni Singapore; Phillipe Marcq, ESPCI Paris). More broadly, the IMB and UQ campus provide a vibrant, multidisciplinary environment for this training, where they will get exposure to disciplines such as developmental biology, gastroenterology and genomics, as well as the cell biology and biophysics of the host lab.

Identifying novel factors that can reduce severity of stroke-prone vascular malformations

Principal Advisor: Dr Anne Lagendijk ( [email protected] )

Associate Advisor: Samantha Stehbens (AIBN/IMB; [email protected] )

Cerebral Cavernous Malformation (CCM) is a progressive vascular disease whereby focal clones of defective endothelial cells give rise to distinctive bulging vascular lesions. The endothelial cells in progressed lesions show reduced adhesion with each other as well as cellular thinning and spreading. CCM lesions form exclusively in venous vessels of the central nervous system (CNS: brain and spinal cord), at a surprisingly high frequency of up to 0.5% of the population. Due to their location and fragile structure CCMs cause chronic headaches, seizures, and stroke. CCM disease is induced by mutations in one of three CCM genes: CCM1, CCM2, or CCM3 which leads to uncontrolled KLF2/4 transcription factor activity.

We recently identified novel factors that are downregulated in CCM disease, and when these factors are fully absent CCM phenotypes worsen. This project will investigate these new players using zebrafish and bioengineered 3D vessel-on-a-chip models and determine these might prevent CCM progression.

Migration dependent signalling in immune cells

Principal Advisor: Prof Jennifer Stow (IMB)

Immune cells migrate through tissues to sites of infection or damage to provide immune defence and to promote tissue repair. Using advanced live cell imaging we can detect trails left by migrating immune cells that help guide other cells to sites of infection. This project will characterise this new form of signalling between cells, uncovering new aspects of immune cell migration vital for fighting infection and wound healing. The project will build skills in cutting edge cell and tissue microscopy and imaging, including in model organisms and organoids, and involve biochemical and genetic analyses. The project is a collaboration between 3 universities with the potential for cross disciplinary research and training in a diverse team.

Peptide absorption in the gastrointestinal tract and development of peptide drugs

This student project is part of a grant-funded industry partnership, with partners at UQ/IMB and Monash U/MIPS and an international pharmaceutical company. As a student member of this team you will receive exceptional training and work experience at the interface between research in academic and industry settings. The project will be part of a broader program investigating how peptides and peptide drugs are absorbed across the wall of the gastrointestinal tract (GIT); multidisciplinary approaches are being taken by the team and the student project will be focussed on using multiple modes of microscopy to examine peptide uptake and distribution. Confocal microscopy, live imaging of cells, organoids, explants and tissues, will be employed, using cutting edge equipment and state of the art technologies; there will be some biochemical and protein studies and you will be involved in quantitative image analysis and handling of big image data. Throughout the project you will work with world class experts for training, supervision and technical innovations. The project will be based at UQ (Brisbane) and involve active interstate and international collaborations. You will emerge from this project with translatable skills, work experience and scientific outputs, having contributed to a project that will have practical outcomes and global impact.

Understanding how inflammation predisposes to cancer

Chronic inflammation of epithelial organs, such as the gut, are known to predipose to cancer. But the mechanisms responsible for this predisposition are poorly understood. Elucidating such mechanisms are essential to identify patients at increased risk for cancer and present novel opportunities to decrease cancer risk.

This project builds on our pioneering discoveries to test how inflammation may increase cancer risk by altering the epithelium within which cancer originates. We recently made the exciting discovery that abnormalities in the mechanical properties of epithelial tissues may increase cancer risk by disabling the tissue's ability to eliminate newly-transformed cancer cells. Understanding how inflammation affects tissue mechanics will provide new opportunities for diagnosis and therapeutics.

This project will provide training in a wide range of modern research approaches, including advanced microscopy, bioengineered systems to study cell behaviour, and animal models of cancer development and elimination.

Principal Advisor: Associate Professor Nathan Palpant ( [email protected] )

Associate Advisors: Dr Sonia Shah ( [email protected] ) and Professor Mikael Boden ( [email protected] )

Despite these powerful approaches, studies indicate that classifying variants as pathogenic occurs in only a minority of cases and among variants reported in ClinVar, a public archive of relationships between human variation and phenotype, wherein a large proportion (37%) are classified as variants of unknown significance (VUS).

This project aims to address this key gap in knowledge, involving work in computational and/or cell biology studies, depending on the student skills and interests. For computational studies, this project aims to develop methods that integrate predictive, genome-wide identifiers of pathogenicity. We will use machine learning to build non-linear prediction methods that outperform individual prediction tools in identifying genetic causes of disease and accelerating clinical diagnosis of genetic diseases. For cell biology studies, we aim to use clinical genetics data (from the Australian Functional Genomics Network) to determine pathogenicity of variants from patients with inherited cardiovascular diseases.

The approaches will include: 1) cell modelling with human pluripotent stem cells (hPSCs), a disease-agnostic and scalable platform for high-throughput hPSC variant screening. To study variants in genes such as transcription factors that are known to cause genetic diseases, we will use molecular phenotyping by genome-wide proximity labelling with DNA adenine methyltransferase (DamID) to study how disease-causing variants alter regulatory control of the genome. Collectively, this aim implements computational predictions with disease modelling as an efficient, scalable, and disease agnostic pipeline to increase the diagnostic rate of unresolved cases.

Unravelling how epithelial tissues detect and respond to cell death and injury.

Principal Advisor: Prof Alpha Yap ( [email protected] )

We propose that a key factor lies in how cells use mechanical forces to communicate with each other. We apply physical and cell biological approaches to understand how those mechanical forces are generated and detected for tissue health and repair. We use innovative approaches from different disciplines, including live-cell microscopy and genetic manipulation in zebrafish embryos; experimental tools and theory from physics that provide new ways to understand the biological phenomena; and testing how failure of mechanical communication may allow injury to disrupt tissue health through inflammation and infection.

Individual projects will be designed that emphasize different aspects within this overall program, tailored for the specific interests of students, which can range from biology to biological physics. Independent of the specific focus of an individual project, the interdisciplinary range of this Laureate Program provides an exciting opportunity for students to train across biological and physical disciplines, to enhance their capacity and versatility for the future.

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

The blood-brain barrier controls the transfer of substances between the blood and the brain, protecting us from toxic compounds while allowing the transfer of nutrients and other beneficial molecules. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. The project will involve cell culture, blood-brain barrier models and assays, proteomics, peptide chemistry, molecular biology and pharmacology. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations relevant to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.

Engineering high-efficiency light-driven synthetic biology

Principal Advisor: Prof Ben Hankerman (IMB)

Every two hours Earth receives enough energy from the sun to power our global economy for a year. The capture and use of this energy are essential to power a sustainable zero CO2 emissions future, increase international fuel security and build advanced light-driven industries as part of an expanding circular bioeconomy.

Over 3 billion years, photosynthetic microorganisms have evolved to tap into the huge energy resource of the sun and use it to synthesise a diverse array of biomolecules that collectively form biomass. This photosynthetic capacity can be adapted to create clean fuels for the future such as hydrogen and an array of high-value biomolecules.

This PhD project is focused on the development of high-efficiency light-driven single cell green algae (microalgae) cell lines that can produce hydrogen fuel from water as well as high-value molecules using advanced genetic “plug-and play” molecular biology techniques.

Building on extensive foundational work, the project will involve the design of expression vectors, cell transformation and screening, creation of specific point mutants and gene knockouts using CRISPR and their characterisation (e.g. photosynthetic physiology, H2 production). The project may extend to technoeconomic analyses of scaled up designs and lab scale validation of the proposed industrial processes.

Associate Advisor: A/Prof Jyotsna Batra (QUT)

Prostate cancer is the second most frequent malignancy in men worldwide, causing over 375,000 deaths a year. When primary treatments fail, disease progression inevitably occurs, resulting in more aggressive subtypes with high mortality. This project focuses on the oxytocin/oxytocin receptor (OT/OTR) signalling system as a potential new drug target and biomarker to improve prostate cancer management and patient survival. Anticipated outcomes include a better understanding of OT/OTR’s role in prostatecancer and new therapeutic leads for an alternative treatment strategy.

Modulating protein-protein interactions in disease

Principal Advisor: Prof David Fairlie (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2025, which means you must apply no later than 30 September, 2024.

Most diseases are mediated by protein-protein interactions, often fleeting contacts between large protein surfaces too shallow to sequester conventional small molecule drugs. This project will design and develop classes of new compounds at and above size limits of conventional drugs to modulate more difficult protein-activated receptors that are largely targets without drugs. To do this, the candidate will first truncate one of the binding partners to a smaller peptide and optimise its structure, composition, protein affinity, and functional potency in order to modulate the protein-protein interaction that leads to disease. This will require knowledge and skills in peptide chemistry, solid phase synthesis, HPLC purification, spectroscopy (NMR, MS, CD), and an ability and motivation to modify peptides into small bioavailable molecules using organic synthesis techniques. Some knowledge of cell biology and enzyme assays would be an advantage, as would knowledge of NMR spectroscopy. The long term goal is to design new compounds and profile them for effects on genes/proteins/cells/rodent models of immunometabolism, inflammatory diseases and cancer. Outcomes will include new knowledge of protein-protein interactions in disease; greater understanding of drug targets, disease mechanisms and effectiveness of new drug action; patentable methods and bioactive compounds; and new experimental drug leads to new medicines for preclinical development towards the clinic.

Molecular design of drugs to fight chronic human diseases and environmental pests

Principal Advisor: Dr Conan Wang (IMB)

Must commence by Research Quarter 3, 2025.

An excellent opportunity for a PhD candidate to explore cutting-edge technologies for design of bioactive proteins to fight chronic human diseases or environmental pests. A motivated individual will be immersed in a leading research institute and international team at UQ, supported by an Australian Centre of Excellence and nationally funded research programs.

Development of drugs for human benefit, whether to cure human diseases or safeguard our food resources and environmental assets, must begin with the design of bioactive lead molecules. This research program will investigate platform technologies for engineering of novel proteins, which are actively pursued by many emerging biotechnology industries. The candidate will choose one of the following major application areas of national importance.

Next-generation anti-cancer drugs
Antimicrobial agents to fight infection
Bio-friendly drugs to control agricultural pests
Natural proteins to prevent crown of thorns starfish outbreaks

A typical project will involve use of protein structure to design new drugs. The candidate could choose to use either computational design tools or molecular libraries to screen massive numbers of drug leads. This often followed by characterisation of structure and activity using biophysical, biochemical and/or biological assays.

Photocontrollable probes to study neuropeptide-mediated memory formation

This project aims at developing next-generation molecular probes with enhanced specificity and spatiotemporal control for the study of proteins and neuropeptide signalling. It addresses recognised knowledge gaps and technical bottlenecks in neuropeptide and memory research. Expected outcomes include a deeper molecular understanding of long-term memory formation and the role of neuropeptides in this process, as well as innovative chemistry strategies and novel molecular probes to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations of relevance to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.

Targeting strategies for drug design

Selective binding of small molecules with proteins underpins most drug discovery. However, while a compound can be devised to interact with a single protein, this cannot drive the molecule into a specific location where functional modulation of the target protein only at that location is desired for therapy. Instead, designed compounds usually bind to the protein wherever it is expressed in the body and this can be deterimental to normal healthy physiology. This project will investigate a number of promising new approaches to directing protein-binding compounds to specific compartments of cells and organisms. It will require a combination of organic synthesis, medicinal chemistry, molecular modelling and chemical biology. The new approaches will be tested and optimised with the goal of inhibiting or activating desired proteins in specific compartments in order to modulate disease-causing protein functions without altering normal healthy physiology. Achieving these aims will require enthusiasm, a high degree of self-motivation, lateral thinking, strong chemical knowledge and hands-on skills in organic synthesis (solution and solid phase), NMR characterisation (including 2D NMR structure analysis), HPLC purification, mass spectrometry, and computer modelling. Some knowledge of enzyme assays and cell biology would be an advantage. The long term goal is to design new compounds and profile them for selective effects on target genes/proteins/cells/rodent models of inflammatory diseases and cancer. Outcomes will include new knowledge of protein function in disease; greater understanding of medicinal and organic chemistry in drug design, drug targeting, mechanisms and effectiveness of drug action; patentable methods and bioactive compounds; and new experimental leads to new medicines for development towards the clinic.

Tuning the activating stimulus of voltage-gated sodium channels

Principal Advisor: Dr Angelo Keramidas (IMB)

This project will investigate how voltage-gated sodium channels, which are proteins (ion channels) found on the surface of neurons (brain cells and nerves) function as molecular conduits of cell-to-cell electrical communication. The overall aim is to study how molecular probes (venom peptides) and structural parts of these ion channels affect the local biophysical environment of the ion channels, and how this leads to fine tuning of the ion channel's sensitivity to the stimulus that activates them (cell membrane voltage).

This project will use natural and modified peptides that are derived from venoms of different species, such as spiders and ants to probe and manipulate the functional properties of an ion channel that is critically important to the function of the nervous system.

The conceptual knowledge gained from this project would advance our understanding of a fundamental physiological process and facilitate the development of drugs that regulate ion channel function, such as antiepileptics, analgesics and insecticides.

Understanding how blood vessels in the brain are formed

Principal Advisor: Dr Rosemary Cater ( [email protected] )

Associate Advisor: Dr Anne Lagendijk ( [email protected] )

The human brain comprises ~650 kilometres of blood vessels lined by brain endothelial cells, which supply the brain with oxygen and essential nutrients. The growth of cerebral blood vessels begins early in development via a process called sprouting angiogenesis. Despite its importance, the molecular mechanisms underlying brain angiogenesis and formation of the blood-brain barrier are poorly understood. It has recently been demonstrated that the gene Flvcr2 is critical for blood vessels to grow in the brain, and last year we discovered that the protein encoded by this gene (FLVCR2) transports choline – an essential nutrient – across the blood brain barrier and into the brain. This project will utilise biochemical techniques and structural biology (cryo-EM) to investigate what other molecules may regulate this transport process, and how choline regulates angiogenesis in the brain.

How bacteria form antibiotic resistant biofilms

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisors: A/Prof Markus Muttenthaler, Prof Waldemar Vollmer (IMB)

Biofilms are surface-attached clusters of bacteria encased in an extracellular matrix. They are a significant problem in many areas that influence our everyday life, including agriculture (e.g. plant and animal infections), industry (e.g. contamination of plumbing, ventilation and food industry surfaces) and medicine (e.g. ~80% of human infections are biofilm associated, including device-related infections). This project will apply molecular microbiology methodsto understand the structure, function and regulation of biofilms produced by uropathogenic E. coli that cause urinary tract infections, and investigate new strategies to disrupt biofilms. The project will build skills in cutting edge genetic screens, molecular microbiology, genome sequencing, bioinformatics, microscopy, imaging and animal infection models. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

Identifying new targets for treatment of antimicrobial resistant infections

Principal Advisor: Prof Ian Henderson (IMB)

Driven by the introduction of antibiotics and vaccines, deaths from infectious diseases declined markedly during the 20th century. These unprecedented interventions paved the way for other medical treatments; cancer chemotherapy and major surgery would not be possible without effective antibiotics to prevent and treat bacterial infections. The evolution and widespread distribution of antibiotic-resistance elements, and the lack of new antimicrobials, threatens the last century of medical advances; without action the annual death toll from drug-resistant infections will increase from 0.5 million in 2016 to 10 million by 2050. New treatments are desperately needed including new antibiotics and alternative treatments such as phage. This project will address the molecular basis for the basis of phage interaction with the bacterial cell envelope and the potential for using this knowledge to treat antibiotic resistant infections.

Genetics of sensory nutrition – using genetics to understand how taste and olfactory perception influences eating behaviour and health

Principal Advisor: Dr Daniel Hwang (IMB)

This project requires candidates to commence no later than Research Quarter 3, 2025, which means you must apply no later than 29 February 2024 .

Human perception of taste and smell plays a key role in food preferences and choices. There is a large and growing body of work suggesting that taste and smell (together known as "chemosensory perception") determine eating behaviour and dietary intake, a primary risk factor of chronic conditions such as obesity, cardiometabolic disorders, and cancer.

However, evidence to date is largely based on observational studies that are susceptible to confounding and reverse causation, leaving the "causal effects" of chemosensory perception on food consumption unclear. If their relationship is truly causal, flavour modification may represent a tangible way of modifying food consumption in a way that benefits public health outcomes.

This PhD project aims to: (i) elucidate the genetic architecture underlying individual differences in taste and smell perception, (ii) use this information to assess their causal effects on eating behaviour, and (iii) create a sensory-food causal network mapping individual sensory qualities (i.e. sweet taste, bitter taste, and more) to individual food items.

The candidate will gain skills in big data analyses, computer programming, statistical method development and application (structural equation modelling, genome-wide association analysis, Mendelian randomisation), and writing and publishing scientific peer-reviewed papers. The candidate will also have opportunities to be involved and to lead national and international collaborative projects.

Sometimes Correlation does Equal Causation: Developing Statistical Methods to Determine Causality Using Genetic Data

Principal Advisor: Prof David Evans (IMB)

There is a well-known mantra that correlation does not necessarily equal causation. This is why randomized controlled trials in which participants are physically randomized into treatment and placebo groups are the gold standard for assessing causality in epidemiological investigations. However, what is less appreciated is that strong evidence for causality can sometimes be obtained using observational data only. In particular, genotypes are randomly transmitted from parents to their offspring independent of the environment and other confounding factors, meaning that genotypes associated with particular traits can be used like natural “randomized controlled trials” to examine whether these traits causally affect risk of disease.

The aim of this PhD project is to develop statistical methods to assess causality using observational data alone. The successful candidate will gain experience across a wide range of advanced statistical genetics methodologies including Mendelian randomization (a way of using genetic variants to investigate putatively causal relationships), structural equation modelling, genome-wide association analysis (GWAS), genetic restricted maximum likelihood (G-REML) analysis of genome-wide data which can be used to partition variation in phenotypes into genetic and environmental sources of variation, and instrumental variables analysis (using natural “experiments” to obtain information on causality from observational data). The candidate will apply the new statistical methods that they develop to large genetically informative datasets like the UK Biobank (500,000 individuals with genome-wide SNP data).

Testing effect of environmental exposures on subsequent human generations

Principal Advisor: Dr Gunn-Helen Moen (IMB)

We are seeking a PhD candidate to join our research team in this exciting project funded by the Australian Research Council. The research group has conducted work within genetic epidemiology, focusing on pregnancy related exposures and outcomes.

Depending on the student’s level of experience and aptitude, they will help develop and/or apply statistical genetics approaches to investigate the possible existence of transgenerational epigenetic effects on human phenotypes.

A PhD is about learning new skills and learning how to do research. Our ideal candidate will have knowledge or keen interest in learning genetics, epidemiology, statistics, unix and shell scripting, and statistical software such as R. You will work closely with an experienced researcher on the project. There will also be possibility for a research stay in Norway during this PhD.

The main purpose of the fellowship is research training leading to the successful completion of a PhD degree.

The advertised projects are fundamentally quantitative and computer-based, and so evidence of aptitude in these areas is essential. The candidate should also have the ability to design, plan, and execute experiments and be proficient in English, both written and oral.

We are looking for someone who is:

Excellent communication and team working skills
Organized and structured
Enthusiastic and willing to learn new methods and techniques

S ubscribe to alerts

Subscribe to be the first to know of new research projects added, new scholarships added, and new opportunities. You'll also be reminded of due dates, get invitations to relevant events and tours, and get updates on the application process.

Subscribe to alerts

General enquiries

+61 7 3346 2222 [email protected]

Student enquiries

PhD and Masters enquiries HDR Liaison Officer [email protected]

All other student enquiries Collaborators Liason [email protected]

Student resources

IMB Research Groups

IMB Research Projects

Scholarship opportunities

Students of IMB Association (SIMBA)

UQ Graduate School

UQ Accessibility Services

UQ Student Centre

UQ Student Services

Stay in touch

Subscribe to alerts Subscribe to newsletter

Alternatively, use our A–Z index

Attend an open day

Discover more about postgraduate research

PhD Management of Projects / Overview

Year of entry: 2024

View full page

The standard academic entry requirement for this PhD is an upper second-class (2:1) honours degree in a discipline directly relevant to the PhD (or international equivalent) OR any upper-second class (2:1) honours degree and a Master’s degree at merit in a discipline directly relevant to the PhD (or international equivalent).

Other combinations of qualifications and research or work experience may also be considered. Please contact the admissions team to check.

Full entry requirements

Apply online

In your application you’ll need to include:

The name of this programme
Your research project title (i.e. the advertised project name or proposed project name) or area of research
Your proposed supervisor’s name
If you already have funding or you wish to be considered for any of the available funding
A supporting statement (see 'Advice to Applicants' for what to include)
Details of your previous university level study
Names and contact details of your two referees.

Programme options

Programme description.

Research in the Department of Mechanical, Aerospace and Civil Engineering covers six broad research themes ; aerospace engineering, innovative manufacturing, modelling and simulation, nuclear engineering, resilient systems, and structures in extreme environments.

Our postgraduate research programmes in Management of Projects offer the opportunity to study in a multi-disciplinary team alongside leading academics in the field.

Drawing on our expertise in conflict and dispute resolution, risk management, contracts and procurement, supply chains and inter-organisational relations and sustainable development we drive innovative solutions to promote successful project management. We have strong links with industry and excellent employability. Visit our research projects page to browse our range of currently available projects.

For entry in the academic year beginning September 2024, the tuition fees are as follows:

PhD (full-time) UK students (per annum): Band A £4,786; Band B £7,000; Band C £10,000; Band D £14,500; Band E £24,500 International, including EU, students (per annum): Band A £28,000; Band B £30,000; Band C £35,500; Band D £43,000; Band E £57,000
PhD (part-time) UK students (per annum): Band A £2393; Band B £3,500; Band C £5,000; Band D £7,250; Band E 12,250

Further information for EU students can be found on our dedicated EU page.

The programme fee will vary depending on the cost of running the project. Fees quoted are fully inclusive and, therefore, you will not be required to pay any additional bench fees or administration costs.

All fees for entry will be subject to yearly review and incremental rises per annum are also likely over the duration of the course for Home students (fees are typically fixed for International students, for the course duration at the year of entry). For general fees information please visit the postgraduate fees page .

Always contact the Admissions team if you are unsure which fees apply to your project.

Scholarships/sponsorships

There are a range of scholarships, studentships and awards at university, faculty and department level to support both UK and overseas postgraduate researchers.

To be considered for many of our scholarships, you’ll need to be nominated by your proposed supervisor. Therefore, we’d highly recommend you discuss potential sources of funding with your supervisor first, so they can advise on your suitability and make sure you meet nomination deadlines.

For more information about our scholarships, visit our funding page or use our funding database to search for scholarships, studentships and awards you may be eligible for.

Contact details

The School of Engineering creates a world of possibilities for students pursuing skills and understanding. Through dynamic research and teaching we develop engineering solutions that make a difference to society in an ethical and sustainable way. Science-based engineering is at the heart of what we do, and through collaboration we support the engineers and scientists of tomorrow to become technically strong, analytically innovative and creative. Find out more about Science and Engineering at Manchester .

Programmes in related subject areas

Use the links below to view lists of programmes in related subject areas.

Management of Projects in Engineering

Regulated by the Office for Students

The University of Manchester is regulated by the Office for Students (OfS). The OfS aims to help students succeed in Higher Education by ensuring they receive excellent information and guidance, get high quality education that prepares them for the future and by protecting their interests. More information can be found at the OfS website .

You can find regulations and policies relating to student life at The University of Manchester, including our Degree Regulations and Complaints Procedure, on our regulations website .

Avoidance links

PhD projects available in the 2024 call

Deciphering the role of the adhesive switch between cadherin and integrin during epithelial cell cytokinesis, formation and maintenance of intestinal microvilli in c. elegans, genetic and epigenetic control of muscle stem cell dynamics for adult muscle repair, door open or closed exploring how aurora kinase a/aurka uses mitochondrial protein import as an entry gate to decode stress signals in breast cancer cells., smart microscopy for allosteric cdk5 inhibitors screen in living cells using high content flim of fret biosensors, understanding the regulation of microtubule structural instability by the processive polymerase xmap215, developing new microscopy tools to investigate parp1 dynamics with the cell nucleus, investigating the role of sumoylation signaling in the sensitivity to parp inhibitors, investigating the interplay between dna repair by ogg1 and transcriptional regulation, live analysis of rarγ-mediated transcriptional regulation during ra-induced differentiation of pluripotent cells, structural characterization of the mechanism of action of trans-translation inhibitors, functional mapping of protein-protein interactions mediated by cullin-ring ubiquitin ligases, modeling shh-dependent midline brain abnormalities using patient-derived stem cells, ocular lens development and disease: toward curing cataracts, rna-based therapy to reach unmet needs in melanoma.

Supervision: Roland Le Borgne Le Borgne lab - Epithelia Dynamics and Mechanics

Abstract Epithelia are robust tissues whose mechanical cohesion requires the formation of cell-cell adhesive contacts supported by adherens junctions (AJs), mainly composed of E-Cadherin clusters stabilized by actomyosin filaments, and cell-matrix adhesive contacts supported by Focal Adhesions (FAs). Thus, AJs and FAs are the two main adhesive structures that ensure the formation of robust mechanical contacts enabling the transmission of cytoskeletal force to support changes in cell and tissue shape. The mechanical sealing properties of epithelia are constantly challenged by cell-cell rearrangements that occur during delamination, intercalation and cell division. During these events, the E-Cadherin contacts are dismantled, yet neighbor exchange occurs without tissue tearing apart. The interplay between actomyosin contractility and the remodelling of AJs are proposed to be sufficient to support these multicellular rearrangements. However, and unexpectedly, we discovered that during cell intercalation and cytokinesis in Drosophila, FAs are transiently assembled at sites of AJ remodeling. Using genetic, super-resolution imaging and biophysical approaches, the PhD student will study FAs assembly, their connection to actomyosin force generators and functions during cytokinesis. Our working hypothesis is that the cleavage furrow ingression at cytokinesis causes a shear stress that triggers the local dismantling of AJs and, concomitantly, the assembly of FAs in the plane of AJs. This multidisciplinary PhD project will provide a comprehensive understanding of the cooperation and interdependence of cadherin and integrin adhesion to ensure tissue tensional homeostasis.

Keywords Epithelia, cell-cell junction, cytokinesis, tissue integrity maintenance

Related publications Thomas Esmangart de Bournonville, Mariusz K. Jaglarz, Emeline Durel, Roland Le Borgne. ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism sensing paracellular diffusion barrier alteration in Drosophila epithelial cells. In minor revision at eLife, 2024. hal-04284641 Thomas Esmangart de Bournonville, Roland Le Borgne. Interplay between Anakonda, Gliotactin and M6 for tricellular junction assembly and anchoring of septate junctions in Drosophila epithelium. Current Biology, 2020, 30(21):4245-4253.e4. hal-03019042 Emeline Daniel , Marion Daude , Irina Kolotuev , Kristi Charish , Vanessa Auld , et al. Coordination of septate junctions assembly and completion of cytokinesis in proliferative êpithelial tissues. Current Biology, 2018, 28(9):1380-1391.e4. hal-01863222

Supervision: Anne Pacquelet - Grégoire Michaux Michaux lab - Dynamics of epithelial polarity

Abstract The apical membrane of the intestinal epithelium presents a network of actin-based microvilli, called the brush border, which is essential for food absorption, mucus secretion and interactions with the microbiome. In this project, we propose to molecularly characterize microvilli growth and maintenance in a living organism, using C. elegans as a model. We recently started to describe the growth and dynamics of microvilli during C. elegans development (Bidaud-Meynard et al, 2021). We will next characterize how major microvilli components contribute to microvilli growth and maintenance by using loss of function approaches and a combination of super-resolution imaging, FRAP measurements and food absorption experiments. We will investigate the role of microvilli factors that we and others have already identified, as well as new microvilli components identified by our collaborator Mike Boxem (Utrecht University, Netherlands) using a proteomic approach. This project will lead to the first in-depth functional characterization of microvilli growth and maintenance in a living organism, paving the way to future studies as a model for human intestinal diseases.

Keywords Intestine, microvilli, actin, microscopy

Expected profile Training in cell biology and/or developmental biology is expected. To comply with the funding agency, candidates must not have resided or carried out their main activity (work, studies, etc.) in France for more than 12 months in the 36 months immediately before their date of recruitment (October 2024).

Related publications Aurélien Bidaud-Meynard, Flora Demouchy, Ophélie Nicolle, Anne Pacquelet, Shashi Kumar Suman et al. High resolution dynamic mapping of the C. elegans intestinal brush border. Development, 2021, 148 (23). hal-03426601v1

Supervision: Hadi Boukhatmi Boukhatmi Lab - Muscle Development and Repair

Abstract Regeneration of skeletal muscles relies upon pools of muscle stem cells (MuSCs) called satellite cells. In homeostatic conditions, MuSCs are quiescent. In response to muscle injury, they get activated, proliferate, migrate to the damaged muscle and fuse to generate new myofibers. While the transcriptional control of MuSCs differentiation has been extensively studied over the past decades, the interplay between transcription factors (TFs) and chromatin regulators in the control of the different steps of MuSC activation and migration remains to be fully elucidated. In this project we will focus on dissecting the coordination between evolutionary conserved TFs and a chromatin modifying enzyme in the control of MuSCs dynamics. Our approach will involve a combination of live imaging, genetic and genomic techniques, as well as functional assays conducted in the model organism, Drosophila. Through this project, we aim to gain a comprehensive understanding of the molecular mechanisms that govern MuSC behavior and muscle regeneration.

Keywords Muscle, regeneration, microscopy, genomics, genetics, Drosophila

Expected profile Strong interest in the field of cell and developmental biology. An ideal candidate would have a background in genetic research, as well as experience in microscopy and/or genome-wide analysis.

Related publications Emma Leroux, Nourhene Ammar, Savannah Moinet, Thierry Pecot, Hadi Boukhatmi. Studying Muscle Transcriptional Dynamics at Single-molecule Scales in Drosophila. Journal of visualized experiments : JoVE, 2023, 199. hal-04260328 Hadi Boukhatmi. Drosophila, an Integrative Model to Study the Features of Muscle Stem Cells in Development and Regeneration. Cells, 2021, 10 (8), pp.2112. hal-03355068 Hadi Boukhatmi and Sarah Bray. A population of adult satellite-like cells in Drosophila is maintained through a switch in RNA-isoforms. eLife, 2018, 7. hal-04260428

Supervision: Giulia Bertolin Bertolin Lab - Mitochondrial Biology and Integration with the Cell Cycle

Abstract Nearly all mitochondrial proteins are encoded by the nuclear genome before being imported into the organelle. It is known that specific import-related proteins are overexpressed in breast cancer cells. In these same models, the overexpression of the cell cycle-related kinase AURKA is frequently observed. We were the first to uncover key roles of AURKA in maintaining mitochondrial functions. However, whether AURKA exerts its mitochondrial functions by interacting with the import machinery and by regulating import flux is currently unknown. To tackle these questions, we will use two Förster’s Resonance Energy Transfer (FRET) biosensors for mitochondrial functions. These tools will be combined with confocal live microscopy, biochemical approaches and with a custom-made library of pharmacological compounds. We will determine if mitochondrial protein import rates are altered in breast cancer cells overexpressing AURKA, and explore import-related strategies to restore mitochondrial functions. Our results will reveal how AURKA controls mitochondrial functions in breast cancer cells, and provide significant breakthroughs of therapeutic interest.

Keywords Mitochondria, AURKA, FRET, import

Related publications Giulia Bertolin , Marie-Clotilde Alves-Guerra , Angélique Chéron , Agnès Burel , Claude Prigent , et al. Mitochondrial Aurora kinase A induces mitophagy by interacting with MAP1LC3 and Prohibitin 2. Life Science Alliance, 2021, 4 (6), pp.e202000806. hal-03248135 Elif Begüm Gökerküçük , Angélique Cheron , Marc Tramier , Giulia Bertolin. The LC3B FRET biosensor monitors the modes of action of ATG4B during autophagy in living cells. Autophagy, 2023,19, 2275–2295. hal-04020162 Rakesh Kumar Sharma , Abderrahman Chafik , Giulia Bertolin. Aurora kinase A/AURKA functionally interacts with the mitochondrial ATP synthase to regulate energy metabolism and cell death. Cell Death Discovery, 2023, 9 (1), pp.203. hal-04163733

Supervision: Marc Tramier Tramier Lab - Microscopy for Cell Biosensing

Abstract The "Microscopy for Cell Biosensing" team develops techniques and methods for the dynamic monitoring of biochemical activities in living cells. The team has already developed a fastFLIM prototype, a FRET biosensor of AurkA kinase activities making it possible to discover new functions of this kinase at the mitochondria, and a screening methodology for inhibitors of the AurkA kinase by HCS-FLIM. We are developing the Roboscope prototype for event-driven acquisition able to analyse images in real time using deep learning algorithms in order to detect cellular event of interest and to feed back the microscope control for adjusting the acquisition sequence (patent pending, collaboration J Pécréaux and Inscoper). We are also developing a CDK5 FRET biosensor based on conformation to study allosteric inhibitors in living cells (projet ITMO Cancer PCSI 2022-2024 in collaboration with M Morris and F Bihel). The project propose to combine these two developments by using the Roboscope in the pipeline of HCS-FLIM for CDK5 allosteric inhibitors screen. It fits perfectly with the team's project which consists in implementing an automated platform which will allow monitoring of different cellular functions particularly in the context of cancer. It will be a first step in the development of quantitative automated microscopy for translational research, and pave the way for its use in drug discovery or personalized medicine.

Keywords Intelligent Microscopy, artificial Intelligence, quantitative fluorescence microscopy, FRET by FLIM, high content screening

Expected profile Strong interest in fluorescence microscopy applied to biology and in machine learning for image analysis

Related publications Giulia Bertolin , Florian Sizaire , Gaëtan Herbomel , David Reboutier , Claude Prigent , et al. A FRET biosensor reveals spatiotemporal activation and functions of Aurora kinase A in living cells. Nature Communications, 2016, 7 (1), pp.12674. hal-01394773 Giulia Bertolin, Anne-Laure Bulteau, Marie-Clotilde Alves-Guerra, Agnes Burel, Marie-Thérèse Lavault et al. Aurora kinase A localises to mitochondria to control organelle dynamics and energy production. eLife, eLife Sciences Publication, 2018, 7, pp.e38111. hal-01862597v1 Florian Sizaire, Gilles Le Marchand, Jacques Pecreaux, Otmane Bouchareb, Marc Tramier. Automated screening of AURKA activity based on a genetically encoded FRET biosensor using fluorescence lifetime imaging microscopy. Methods and Applications in Fluorescence, IOP Science, 2020, 8 (2), pp.024006. hal-02500623v1

Supervision: Denis Chrétien, Romain Gibeaux Gibeaux lab - Microtubules, from Tubulin to Spindles

Abstract Microtubules are cytoskeletal elements that are essential to various cellular functions that they ensure thanks to their dynamic instability. We recently showed that microtubules assembled from pure tubulin are structurally heterogeneous. Strikingly, we observed similar lattice heterogeneity in microtubules assembled from cytoplasmic extracts, albeit at a much reduced rate suggesting that this intrinsic behavior is tightly regulated in cells. We envision that microtubule intrinsic dynamic instability is intimately linked to their structural instability. We moreover propose that, in cells, End-Binding proteins control the quality of the microtubule lattice to correct errors that happen during elongation and that are enhanced by polymerases such as XMAP215. Using cryo-electron tomography and TIRF microscopy approaches at purified protein and cytoplasmic extract levels, our aim is to characterize how dynamic instability is triggered by, and reciprocally allows the correction of microtubule lattice defects. In this project, we will particularly investigate the role of XMAP215, as a potential low-fidelity polymerase, in modulating microtubule structural instability and thus its dynamic instability.

Keywords Microtubule, dynamic instability, structural instability, cryo-electron tomography

Related publications Charlotte Guyomar , Clément Bousquet , Siou Ku , John M Heumann , Gabriel Guilloux , et al. Changes in seam number and location induce holes within microtubules assembled from porcine brain tubulin and in Xenopus egg cytoplasmic extracts. eLife, 2022, 11, pp.e83021. hal-03923259 Juan Estévez-Gallego , Fernando Josa-Prado , Siou Ku , Ruben Buey , Francisco Balaguer , et al. Structural model for differential cap maturation at growing microtubule ends. eLife, 2020, 9, pp.e50155. hal-02552246 Audrey Guesdon , Franck Bazile , Ruben M. Buey , Renu Mohan , Solange Monier , et al. EB1 interacts with outwardly curved and straight regions of the microtubule lattice. Nature Cell Biology, 2016, 18 (10), pp.1102-1108. hal-01394776

Supervision: Sébastien Huet Salbert Lab - Spatio-temporal regulation of transcription and repair

Abstract Poly-ADP-ribose polymerase 1 (PARP1) is a key actor of the DNA damage response of the cell. If PARP1 recruitment at DNA breaks is important for repair, its timely release is also crucial to avoid deleterious consequences. Indeed, the cytotoxicity of PARP inhibitors used against BRCA-deficient tumors originates from the trapping of inhibited PARP1 on DNA lesions. Nevertheless, recent data show that inhibited PARP1 molecules are not stably bound to DNA lesions in living cells, calling for a better description of the trapping mechanism. In this project, that will involve a close collaboration between the Huet (IGDR, Rennes) and the Hinde (University of Melbourne) labs, we will setup a multiscale analysis framework based on fluorescence imaging to better characterize PARP1 dynamics in living cells. This approach will be used to retrieve the large range of dynamics displayed by PARP1 in the nucleus and to characterize its transient association with endogenous and exogenous DNA lesions. This project will improve our description of the mechanisms underlying the exploration of the nuclear space by PARP1 while searching for DNA lesions as well as the impact of clinically-relevant inhibitors on these dynamics.

Keywords Cancer, DNA repair, PARP, fluorescence microscopy

Related publications Rebecca Smith , Siham Zentout , Magdalena Rother , Nicolas Bigot , Catherine Chapuis , et al. HPF1-dependent histone ADP-ribosylation triggers chromatin relaxation to promote the recruitment of repair factors at sites of DNA damage. Nature Structural and Molecular Biology, 2023, 30, 678-691. hal-04089195 Jieqiong Lou, David G Priest, Ashleigh Solano, Adèle Kerjouan, Elizabeth Hinde. Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break. Nature Communications, 2020, 11, 5776. PMC7666136

Abstract PARP inhibitors (PARPi) are currently used in the clinic to treat breast and ovarian tumors displaying BRCA mutations and their indications is rapidly growing. Nevertheless, a main drawback of the PARPi-based treatment is the high risk of resistance. The trapping of PARP1 on DNA lesions has been shown as a key driver of PARPi cytotoxicity and therefore, cellular mechanisms affecting trapping are though to modulate PARPi efficacy. This project aims to better understand SUMOylation-dependent PARP1 untrapping and assess the therapeutic potential of the co-inhibition of SUMOylation signaling and PARP1 by combining biochemistry and cell biology assays with live-cell fluorescence imaging. In particular, we hypothesize that, in PARPi-treated cells, SUMOylation could rescue the loss of ADP-ribosylation on PARP1 and nucleosomes, which could directly promote the dissociation of PARP1 from the lesions. Altogether, this project will bring new insights on the so-far overlooked question of the impact of SUMOylation signaling on PARPi efficacy, paving the way for the development of new PARPi-based cancer treatments with reduced risk of resistance.

Related publications Evgeniia Prokhorova , Florian Zobel , Rebecca Smith , Siham Zentout , Ian Gibbs-Seymour , et al. Serine-linked PARP1 auto-modification controls PARP inhibitor response. Nature Communications, 2021, 12 (1), pp.4055. hal-03282381 Szilvia Juhász , Rebecca Smith , Tamás Schauer , Dóra Spekhardt , Hasan Mamar , et al. The chromatin remodeler ALC1 underlies resistance to PARP inhibitor treatment. Science Advances , 2020, 6 (51). hal-03099309

Abstract Oxidative stress induces a plethora of DNA lesions, among which 8-oxoguanine (8-oxoG), a product of guanine oxidation, is the most abundant one. 8-oxoG is a highly mutagenic lesion that is repaired by the base excision repair (BER) pathway, the first step of which is the recognition and excision of the modified base by the DNA glycosylase OGG1. Finding 8-oxoG in the context of nuclear architecture in which the DNA is highly compacted in chromatin is a challenging task for OGG1. Our previous data claim for a finely tuned coordination between BER and transcription but the exact mechanisms underlying this coordinated process remain unknown. In order to get further insights on these mechanisms, the current project aims to characterize how OGG1 searches for 8-oxoG lesions within the cell nucleus and how this search process is impacted by transcription regulators as such as the Mediator subunits. This analysis will be performed directly in living cells by developing advanced fluorescence microscopy tools to characterize OGG1 dynamics at multiple scales in space and time.

Keywords Cancer, DNA repair, transcription, OGG1, fluorescence microscopy

Related publications Ostiane d'Augustin , Virginie Gaudon , Capucine Siberchicot , Rebecca Smith , Catherine Chapuis , et al. Identification of key residues of the DNA glycosylase OGG1 controlling efficient DNA sampling and recruitment to oxidized bases in living cells. Nucleic Acids Research, 2023, 51, 4942-4958. hal-04088267v2 Emilie Lebraud , Guillaume Pinna , Capucine Siberchicot , Jordane Dépagne , Didier Busso , et al. Chromatin recruitment of OGG1 requires cohesin and mediator and is essential for efficient 8-oxoG removal. Nucleic Acids Research, 2020, 48, 9082-9097. hal-02909621

Supervision: Gérard Benoit Salbert Lab - Spatio-temporal regulation of transcription and repair

Abstract Most recent advances in transcription analysis demonstrate that genes are transcribed in a highly dynamic discontinuous pattern referred to as RNA bursting. Understanding this process and its regulation by specific transcription factors at the single cell and single locus level and at the pertinent time scale remains a challenging task. Our project aims at deciphering the dynamic interplay between an endogenous TF, the Retinoic Acid Receptor RARγ and its natural enhancer/promoter targets in the biological context of RA-induced ES cells differentiation. Using genetically engineered cell lines and advanced live-cell fluorescence microscopy tools (SPT, FCS), we aim at analysing RARγ nuclear dynamics and binding events in conjunction with the dynamical expression of its target genes with unprecedented precision. This project will both provide new fundamental knowledge in transcription regulatory process and enhancer/promoter functions and contribute to our understanding of their alteration in pathological processes.

Keywords Retinoic acid receptors, transcription, pluripotent cells differentiation, live-imaging, single cell

Related publications Amandine Chatagnon, Philippe Veber, Valérie Morin, Justin Bedo, Gérard Triqueneaux, Marie Sémon, Vincent Laudet, Florence d'Alché-Buc, Gérard Benoit. RAR/RXR binding dynamics distinguishes pluripotency from differentiation associated cis -regulatory elements. Nucleic Acids Research, 2015, 43(10):4833-54. PMC4446430 Diana A Stavreva, David A Garcia, Gregory Fettweis, Prabhakar R Gudla, George F Zaki, et al. Transcriptional Bursting and Co-bursting Regulation by Steroid Hormone Release Pattern and Transcription Factor Mobility. Molecular Cell, 2019, 75(6):1161-1177.e11. PMC6754282

Supervision: Emmanuel Giudice, Olivier Delalande Gillet Lab - Quality Conrol in Protein Sythesis

Abstract The development of antibiotic-resistant microorganisms is one of the major public health issues of our century. In this context, the present project is to characterize the mechanism of action of antimicrobial molecules aimed at a new target: trans-translation. Trans-translation refers to a molecular process which allows for the release of ribosomes stalled on faulty mRNAs that lack stop codons as well as the elimination of these mRNAs and mistranslated peptides. The process is performed by the hybrid transfer-messenger RNA (tmRNA) and a small basic protein: SmpB. Essential for the survival and/or virulence of many pathogenic bacteria and absent in eukaryotes, trans-translation is a particularly attractive targets for new antibiotics. Using our recently developed HTS screening assays, we discovered a family of heterocyclic compounds that specifically targets trans-translation. The PhD student will be recruited to characterize structurally (cryo-EM, X-ray) and computationally (MD, docking, molecular modeling) these inhibitors on their molecular targets (tmRNA, SmpB and the ESKAPE ribosome’s), in order to understand their mode of action and improve their efficiency and specificity.

Keywords Ribosome, trans-translation, antibiotics, cryo-EM, molecular modelling

Expected profile Biochemist or bioinformatician with basic knowledge in structural biology and/or image analysis. Programming skills in Shell and knowing how to use Linux are a plus. Cryo-EM and modeling techniques can be acquired during the thesis.

Related publications Charlotte Guyomar, Marion Thepaut, Sylvie Nonin-Lecomte, Agnès Méreau, Renan Goude et al. Reassembling green fluorescent protein for in vitro evaluation of trans-translation. Nucleic Acids Research, Oxford University Press, 2020, 48 (4), pp.e22-e22. hal-02440937v1 Charlotte Guyomar, Gaetano D’urso, Sophie Chat, Emmanuel Giudice, Reynald Gillet. Structures of tmRNA and SmpB as they transit through the ribosome. Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.4909. hal-03343248v1 Rodrigo Campos-Silva, Gaetano d'Urso, Olivier Delalande, Emmanuel Giudice, Alexandre Jose Macedo et al. Trans-Translation Is an Appealing Target for the Development of New Antimicrobial Compounds. Microorganisms, 2022, 10 (1). hal-03575603v1

Supervision: Gwenaël Rabut Rabut Lab - Ubiquitylation system Abstract Cullin-RING ubiquitin ligases (CRLs) are essential regulators of numerous cellular processes, including progression through the cell cycle, DNA metabolism, and cell signaling. CRLs mediate the ubiquitylation of a broad spectrum of intracellular proteins, thereby modulating their activity. CRLs function by utilizing substrate adaptor subunits, which directly interact with their protein targets. However, several CRL substrate adaptors are still ‘orphan’ with no known substrates. In this PhD project, we propose to systematically map protein-protein interactions mediated by CRL substrate adaptors, using budding yeast as a model organism. We have previously demonstrated that the NanoLuc Binary Technology (NanoBiT) can be employed to monitor the ubiquitylation of endogenous yeast proteins and to identify CRL interaction partners with a remarkable sensitivity. We will take advantage of this methodology to identify and functionally characterize interacting partners of CRL substrate adaptors. The results of this project will provide the foundation for a more profound understanding of the molecular functions of CRLs and aid in identifying potential opportunities for therapeutic intervention by targeting these ubiquitin ligases. Keywords Ubiquitin, proteasome, protein posttranslational modification, DNA-damage, cancer, neurodegenerative diseases

Related publications Matthew D Petroski, Raymond J Deshaies. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol, 2005, 6(1):9-20. PMID-15688063 Marie Le Boulch, Audrey Brossard, Gaëlle Le Dez, Sébastien Léon, Gwenaël Rabut. Sensitive detection of protein ubiquitylation using a protein-fragment complementation assay. Journal of Cell Science, Company of Biologists, 2020, 133 (12), pp.jcs240093. hal-02635146v1 Lazarewicz, N., Le Dez, G., Cerjani, R., Runeshaw, L., Meurer M., Knop, M., Wysocki, R., and Rabut, G. Accurate and sensitive proteome-scale mapping of protein interactions using a quantitative protein-fragment complementation assay. 2024. Submitted

Supervision: Valérie Dupé Dupé Lab - Genetics of disorders related to Neurectodermal development

Abstract Genetic factors play a major role in the development of brain midline defects, which are characterized by disruptions in the Sonic Hedgehog (SHH) signalling pathway. With this understanding, the objective of this project is to develop innovative methods to improve the molecular diagnosis and deepen our comprehension of the pathophysiology of brain midline defects. A significant challenge in studying this disorder is the inability to access the primary affected tissue, the anterior neuroectoderm. Therefore, this research will employ patient-derived stem cells (iPSCs) to generate neuroectoderm tissue. The impact of variants in the DISP1 gene, encoding the protein that secretes SHH, will be evaluate on cell differentiation, SHH secretion and transcriptomics in differentiated-neuroectoderm tissue. Most importantly, this investigation will demonstrate the relevance of the human iPSC approach to improving the rate of diagnosis of developmental disorders.

Keywords Neurodevelopmental disorders, human IPSC, Sonic Hedhehog, brain development, gene regulation

Expected profile Strong interest in cellular and developmental biology

Related publications Artem Kim , Clara Savary , Christèle Dubourg , Wilfrid Carré , Charlotte Mouden , et al. Integrated clinical and omics approach to rare diseases novel genes and oligogenic inheritance in holoprosencephaly. Brain - A Journal of Neurology , 2019, 142 (1), pp.35-49. hal-01975696 Houda Hamdi-Roze , Michelle Ware , Hélène Guyodo , Aurélie Rizzo , Leslie Ratié , et al. Disrupted hypothalamo-pituitary axis in association with reduced SHH underlies the pathogenesis of NOTCH-deficiency. Journal of Clinical Endocrinology and Metabolism, 2020, 105 (9), pp.dgaa249. hal-02635120 Lavillaureix L, Rollier P, Kim A, Panasenkava V, De Tayrac M, et al. DISP1 deficiency: monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations. Genetics in Medecine, 2024.

Supervision: Carole Gautier-Courteille, Luc Paillard Paillard Lab - Gene Expression and Development

Abstract Opacification of the ocular lens, or cataract, is the first cause of blindness worldwide. A better understanding of the pathophysiological mechanisms that cause cataract as well as the quest for innovative treatments are highly needed. Depending on their wishes and skills, the recruited PhD student will enter either of these two thematics: - Characterize the molecular, genetic and cellular modifications that occur in lens organoids when cataract is induced. The goal is to identify potential druggable targets to devise molecular compounds aimed at counteracting cataract in preclinical models. - Decipher the post-transcriptional controls of gene expression that are at play during lens development. Specifically, a lack of the RNA-binding protein CELF1 leads to cataract in mice and to a similar phenotype in lens organoids. The recruited PhD student will characterize the functional relationships between defective gene expression in the absence of CELF1 and cataract onset

Keywords Eye, disease, RNA regulation, cataract, lens

Expected profile Interest in molecular and cellular biology. A part of the thesis may take place in the lab of our collaborator in the US (Pr Salil Lachke, University of Delaware). Hence, an appetence for international mobility will be appreciated.

Related publications Matthieu Duot , Roselyne Viel , Justine Viet , Catherine Le Goff-Gaillard , Luc Paillard , et al. Eye Lens Organoids Made Simple: Characterization of a New Three-Dimensional Organoid Model for Lens Development and Pathology. Cells, 2023, 12 (20), pp.2478-2478. hal-04265981 Archana D. Siddam , Matthieu Duot , Sarah Y. Coomson , Deepti Anand , Sandeep Aryal , et al. High-Throughput Transcriptomics of Celf1 Conditional Knockout Lens Identifies Downstream Networks Linked to Cataract Pathology. Cells, 2023, 12 (7). hal-04093501 Archana D Siddam , Carole Gautier-Courteille , Linette Perez-Campos , Deepti Anand , Atul Kakrana , et al. The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development. PLoS Genetics, 2018, 14 (3), pp.e1007278. hal-01773341

Supervision: Marie-Dominique Galibert Galibert Lab - Gene Expression and Oncogenesis

Abstract During the last decades, a better understanding of the immunology of the tumors allowed to propose innovative immunotherapies. However only 30% of patients in average do respond. Also advances in genomics permitted to delineate the genetic landscape of cancer and the development of targeted therapies, mainly tyrosine kinase inhibitors and neutralizing antibodies. Yet, resistance emerged and genetic alterations failed to be targeted underscoring the need to develop new approaches. Cutaneous melanoma constitutes one of the best paradigms to picture these progresses and pitfalls. The present PhD project aims to develop RNA-based targeted therapy, using allele specific antisense oligonucleotide (ASO) to target specifically oncogenic driver and reach this unmet need. The project aims i) to design and select ASOs to target specifically the mutated transcript and abrogate the expression of the constitutively active mutated protein, ii) to determine the in vitro and in vivo capacities of ASOs to abrogate the proliferation of mutated melanoma cells and iii) to optimize ASO delivery.

Keywords RNA-targeted therapy, melanoma, genetic regulation

Related publications Anais Paris , Nina Tardif , Francesca M Baietti , Cyrille Berra , Héloïse M Leclair , et al. The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma. EMBO Molecular Medicine, 2022, 14 (12), pp.e15677. hal-03837033 Anais M. Quemener , Laura Bachelot , Anne Forestier , Emmanuelle Donnou-Fournet , David Gilot , et al. The powerful world of antisense oligonucleotides: From bench to bedside. Wiley Interdisciplinary Reviews-RNA, 2020, 11 (5), pp.e1594. hal-02565099 David Gilot , Mélodie Migault , Laura Bachelot , Fabrice Journé , Aljosja Rogiers , et al. A non-coding function of TYRP1 mRNA promotes melanoma growth. Nature Cell Biology, 2017, 19 (11), pp.1348-1357. hal-01647130

Cookies: How we use information on our website:

We use cookies on our website to make it clear, useful and reliable.In order to achieve this and to provide certain personalised features we store a small amount of data about you. To learn more visit Cookies: How we use the information on our website. By navigating from the front page to other sections of our website, you are consenting to information being stored.

2024 PhD Projects

Any of the projects listed below can be selected if you wish to apply for a NIHR Maudsley BRC 3-year PhD studentship to commence October 2024. These projects are categorised by the primary NIHR Maudsley BRC strategic goal applicable to each research study.

As many projects align with more than one strategic goal and more than one BRC research theme, we recommend you refer to all categories to ensure you consider all potential projects that interest you.

Information about the work taking place in each of the NIHR Maudsley BRC research themes is available on our Research pages.

Please refer to individual projects for full information, including the supervisory team, contact email addresses and two key publications. Applicants are encouraged to contact supervisors to discuss the project/s they are interested in applying for.

Novel Therapeutics

We develop innovative pharmacological, psychological, and digital interventions across disorders supported by our Experimental Medicine and Novel Therapeutics and Trials and Prediction themes, to develop and test interventions.

CO24-001: Characterising excitatory-inhibitory synaptic dysfunction in schizophrenia using ultra-high field MRI. Keywords: Schizophrenia; Experimental medicine; Neuroimaging; Glutamate; GABA.

Supervisors

Professor Alice Egerton Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/alice.egerton

Dr Nicolaas Puts Department of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/nick-puts

Dr Cathy Davies Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected]

Project Details

Background: This project uses advanced brain imaging techniques to characterise glutamatergic (excitatory, E) and GABAergic (inhibitory, I) synaptic function in schizophrenia. E/I synaptic function is fundamental to schizophrenia and thus a major target for novel drug development. Progress in this area is impeded by a lack of suitable measures of E/I function in the living human brain, against which novel compounds could be tested during early clinical development.

This project will use ultra-high field (7T) MRI and functional magnetic resonance spectroscopy (fMRS) to measure brain glutamatergic and GABAergic dynamics in people with a diagnosis of schizophrenia and healthy volunteers. It will go beyond collecting single static measures of glutamate or GABA concentration, as has been done previously, and examine the dynamic changes in glutamate / GABA which occur during visual stimulation, and the orderliness / complexity of glutamate and GABA signals, which may respectively better reflect E/I synaptic activity and synaptic dynamics. The project focuses on people with treatment resistant schizophrenia (TRS), and cognitive symptoms – which are the areas in greatest need for new therapeutics.

Together with the research team, the student will recruit and assess study participants and acquire MRS data. They will use and adapt an existing analytical platform and large healthy volunteer dataset for glutamate / GABA dynamics at 3T to the study data at 7T for their analyses.

Novelty and importance: Application of fMRS to study E/I synaptic function in schizophrenia is novel, and only recently possible since installation of the KCL 7T scanner. The PhD should deliver a neuroimaging platform against which potential interventions can be tested in future experimental medicine studies.

Primary aim: To characterise E/I synaptic function and dynamics in relation to TRS and cognition.

Study design and sample size: Case control neuroimaging study; 3 groups (healthy volunteers, TRS, remitted schizophrenia), n = 25/group.

Planned research methods and training provided:

Application of case-control, neuroimaging, and translational approaches to mental health.
Recruitment and assessment of study participants
7T fMRS data acquisition and analyses
Academic writing, presentation and publication, transferable skills

Objectives / project plan:

Year 1: Completion of compulsory and bespoke training; participant recruitment, data acquisition; adaptation of fMRS dynamics platform at 3T to 7T and publication of this work; introduction to PhD thesis.

Year 2: Participant recruitment, data acquisition; data analyses.

Year 3: Complete data analyses, prepare publications, finalise thesis including overall discussion.

Two representative publications from supervisors

Publication 1: Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis. Merritt, K., et al., Egerton A., 2023. Molecular Psychiatry doi: 10.1038/s41380-023-01991-7.

Publication 2: Pasanta, D., He, J. L., Ford, T., Oeltzschner, G., Lythgoe, D. J., & Puts, N. A. (2022). Functional MRS studies of GABA and glutamate/Glx - A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews , 144 , 104940. https://doi.org/10.1016/J.NEUBIOREV.2022.104940

Maudsley BRC research themes

Psychosis and Mood Disorders
Neuroimaging
Experimental Medicine and Novel Therapeutics

CO24-002: Identifying Drug Repositioning Opportunities Through Leveraging the Core Neurogenetics of Psychiatric Disorders Keywords: Major depressive disorder; Eating disorder; Drug discovery; Statistical Genetics; Bioinformatics.

Professor Gerome Breen Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/gerome-breen & https://kclpure.kcl.ac.uk/portal/gerome.breen.html

Dr Jonathan Coleman Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/jonathan.coleman.html

Background: There is an urgent need for new psychiatric drugs, particularly for major depressive disorder (MDD) and eating disorders (ED). Current MDD therapies only work for a minority, and few drugs are approved for ED.

Information from genome-wide association studies (GWAS) could identified prioritized targets within disorder-associated regions, reducing drug development time and costs. The Psychiatric Genomics Consortium (PGC) has identified >550 genetic variants associated with major depression, significantly enriched for the targets of approved antidepressants. ED GWAS has identified associations with anorexia nervosa and with binge eating.

Novelty and importance: This studentship will use the largest genetic datasets available for MDD and ED to identify drug repositioning opportunities. This will provide direct hypotheses for functional validation, leading to new clinical trials addressing key therapeutic needs.

Primary aims:

Aim 1: Expand an existing bioinformatic pipeline for identifying drugs and small molecules to integrate new approaches, and to include information about uncommon, rare, and structural variants.

Aim 2: Use an MDD GWAS adjusted for specific confounders to re-weight MDD GWAS meta-analyses from international consortia and use these reweighted meta-analyses to identify drugs and small molecules for MDD.

Aim 3: Use data on rare and uncommon variants from a large long-read sequencing study of 4000 ED participants to enrich common variant ED GWAS data and conduct analyses to identify drugs and small molecules for ED.

Study design and sample size: The project will expand the bioinformatic tools used by our existing drug repositioning pipeline (Drug Targetor) with existing and emerging tools. Methodological innovation is possible, particularly in integrating rare and structural variation.

MDD data from PGC-MDD will be supplemented by a GWAS adjusted for specific confounders (such as BMI) using data from 120K+ severe MDD cases from the Genetic Link to Anxiety and Depression (GLAD) study, UK Biobank, and from Dutch and Australian collaborators. Together these form the largest extant collection of MDD GWAS data, well powered to detect drug-related phenotypes (as demonstrated in the forthcoming PGC MDD paper).

ED data from PGC-ED will be supplemented with long-read sequencing from 4000 individuals with ED. This is the most powerful dataset available in ED, with deep coverage of different types of genetic variation.

Planned research methods and training provided: The student will develop a Snakemake pipeline applicable to GWAS summary statistics, flexibly incorporating suitable languages (R, Python). Training will be provided by the supervisors, supplemented by local collaborations and specialist training courses.

Prof Breen is the co-PI of the GLAD study and an internationally recognised expert in psychiatric genetics, with a strong interest in leveraging GWAS for drug discovery.

Dr Coleman is a statistical geneticist with extensive experience in the conduct of GWAS and its use in developing empirically testable hypotheses in neurobiology.

Year 1: Training in genetic methods for Aims 2 and 3. Begin pipeline expansion, and train in programming as needed.

Year 2: Apply pipeline to MDD GWAS (Aim 2) and continue pipeline development for Aim 3.

Year 3: Complete and publish Aim 3. Publish pipeline as Aim 1.

Publication 1: Coleman JRI, Gaspar HA, Bryois J; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Breen G. The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biol Psychiatry. 2020 Jul 15;88(2):169-184. doi: 10.1016/j.biopsych.2019.10.015. Epub 2019 Nov 1. PMID: 31926635; PMCID: PMC8136147.

Publication 2: Gaspar HA, Gerring Z, Hübel C; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Middeldorp CM, Derks EM, Breen G. Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder. Transl Psychiatry. 2019 Mar 15;9(1):117. doi: 10.1038/s41398-019-0451-4. PMID: 30877270; PMCID: PMC6420656.

Eating Disorders and Obesity
Trials, Genomics and Prediction

CO24-003: Developing and evaluating a low-cost mechanism for delivering pragmatic randomised controlled trials of digital mental health therapies for young people Keywords: Digital health; Clinical trials; Children and adolescents; Mental health; Informatics.

Dr Johnny Downs Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/johnny-downs

Dr Alice Wickersham Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/alice-wickersham

Professor Edmund Sonuga-Barke Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience

Background: Randomized controlled trials (RCT) are the most rigorous method to examine causal relationships between an intervention and outcome. They are fundamental to the development of evidence-based treatments in children and young people, but are difficult to conduct. Conventional RCTs carry additional burden on participants and researchers in the form of in-person recruitment and appointments, leading to reduced participation and greater loss to follow-up. These factors disproportionately affect young people and caregivers with mental illnesses.

Novelty and importance: One approach to tackling this issue is through the adoption of pragmatic, virtual clinical trials, where assessment and data collection do not occur in traditional clinical settings, but are facilitated via remote interaction. These can confer benefits by facilitating faster recruitment across a greater geographic area while retaining the investigative team at one site. By developing such a platform in collaboration with users, this project will enable us to conduct virtual trials at scale, strengthening our capacity to accelerate translation of innovative mental health interventions into practice following rigorous trial testing.

Primary aims: This project will investigate how a virtual data collection platform called myHealthE could be adapted to provide rapid triage, e-recruitment and delivery of digital mental health therapeutic trials in young people.

Study design and sample size: A secondary data analysis of myHealthE users will comprise over 10,000 families who have signed up to the platform. The subsequent development and testing of the virtual trial platform will involve stakeholder engagement with at least 30 different stakeholders, including young people, caregivers, researchers, software engineers, and clinicians.

Planned research methods and training provided: The student will receive training on:

Conducting systematic review
Advanced epidemiological approaches
Rapid synthesis of qualitative data from co-design workshops and interviews
Inclusive design methodologies
Clinical governance frameworks for implementing digital products within NHS services
Clinical trial methodologies

Year 1: Identify the core requirements for developing a virtual trial platform in child and adolescent mental health settings through a systematic review of academic and grey literature.

Year 2: Identify sociodemographic and clinical factors potentially associated with low engagement with a virtual trial platform, by quantifying the differential uptake of myHealthE.

Year 3: Use a co-design approach with clinicians, researchers, young people and caregivers to develop and test a versatile, virtual trial platform that can be used in clinical populations of young people with mental health disorders.

Publication 1: Kostyrka-Allchorne, K., Chu, P., Ballard, C., Lean, N., French, B., Hedstrom, E., Byford, S., Cortese, S., Daley, D., Downs, J., Glazebrook, C., Goldsmith, K., Hall, C.L., Kovshoff, H., Kreppner, J., Sayal, K., Shearer, J., Simonoff, E., Thompson, M.,& Sonuga-Barke, E.J. (2023). Remote Recruitment Strategy and Structured E-Parenting Support (STEPS) App: Feasibility and Usability Study. JMIR Pediatrics and Parenting , 6(1), e47035.

Publication 2: Morris, A.C., Ibrahim, Z., Heslin, M., Moghraby, O.S., Stringaris, A., Grant, I.M., Zalewski, L., Pritchard, M., Stewart, R., Hotopf, M., Pickles, A., Dobson, R.J.B., Simonoff, E. and Downs, J. (2023). Assessing the feasibility of a web‐based outcome measurement system in child and adolescent mental health services–myHealthE a randomised controlled feasibility pilot study. Child and Adolescent Mental Health , 28(1), 128-147.

Child Mental Health and Neurodevelopmental Disorders
Informatics

CO24-004: Mechanisms of action of external trigeminal nerve stimulation in children with ADHD Keywords: ADHD; Trigeminal nerve stimulation (TNS); fMRI; Actimeter; RCT.

Professor Katya Rubia Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: Professor Katya Rubia (kcl.ac.uk) & https://www.kcl.ac.uk/research/attens-project

Dr Matthew Hollocks Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/matthewhollocks

Professor Mitul Mehta Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected]

Background: Trigeminal nerve stimulation (TNS) is the first non-pharmacological ADHD treatment approved in 2019 by the FDA, although efficacy data do not exist beyond a pilot study on 62 children with ADHD which showed improvement of symptoms after 4 weeks of nightly treatment with medium effect size; furthermore, mechanisms of action are not understood. TNS is a safe, non-invasive neuromodulation that sends low electrical pulses under the skin on the forehead targeting the trigeminal system that activates the locus-coeruleus arousal system and its fronto-thalamic connections, typically under-functioning in ADHD.

Novelty and importance: The study will confirm in a multi-center RCT whether TNS is an effective novel non-drug treatment for ADHD. The PHD specifically will elucidate the so far unknown mechanistic aspects of TNS.

Primary aims: To test effects of TNS on 1) fMRI brain function 2) objective hyperactivity, heart rate variability and electrodermal activity 3) to test mediators/predictors of treatment response.

Study design and sample size: A confirmatory phase IIB, sham-controlled, parallel-arm, blinded, multicenter RCT on the effects of 4 weeks of real versus sham TNS in 150 ADHD children on ADHD symptoms, other clinical problems, executive functions, fMRI brain function and objective physiological data. We will randomise 150 children and adolescents, 8-18 years, with ADHD to real or sham TNS over 4 weeks across London and Southampton, to test whether TNS improves parent-rated ADHD symptoms (primary outcome), cognitive performance and other clinical, fMRI and physiological measures measured at baseline and after 4 weeks. This PhD will focus on the mechanistic fMRI brain function and physiological measures.

Planned research methods and training provided: The PhD will analyse 1) effects of real versus sham TNS on fMRI data in a subgroup of 56 ADHD children, measured in 3 fMRI tasks and a resting scan. (S)he will be trained in fMRI activation and functional connectivity analyses (SPM, FSL). 2) underlying effects of TNS on heart rate variability, electrodermal activity and objective hyperactivity measured on an E4 Empatica actimeter device. The student will be trained in actimeter data analysis (SPSS). 3) mediators, moderators and predictors of treatment response on the main outcome measure, the ADHD-RS, based on all baseline data. The student will be trained in structured mediation analyses to explore mediating and moderating effects and logistic regression models to test response predictors based on all baseline measures using a reduction > 20% in ADHD-RS symptoms.

Year 1: fMRI data analysis and write-up of ~ 7 papers (3 papers on brain activation and 4 papers on functional connectivity measures for resting state and tasks).

Year 2: Analysis of the actimeter data and paper write-up.

Year 3: Analysis of predictors, mediators and moderators of treatment response and paper write-up. Write-up of PHD thesis.

Publication 1: Westwood SJ, Criaud M, Lam SL, Lukito S, Wallace-Hanlon S, Kowalczyk OS, Kostara A, Mathew J, Agbedjro D, Wexler BE, Cohen Kadosh R, Asherson P, Rubia K (2023) Transcranial direct current stimulation (tDCS) combined with cognitive training in adolescent boys with ADHD: a double-blind, randomised, sham-controlled trial. Psychol Med. 53(2):497-512

Publication 2: Westwood SJ, Conti AA, Tang W, Xue S, Cortese S, Rubia K. (2023) Clinical and cognitive effects of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders: a systematic review and meta-analysis. Mol Psychiatry. doi: 10.1038/s41380-023-02227-4. Online ahead of print

CO24-005: Improving body acceptance in young people at risk of eating disorders and those with manifest eating disorders through VR body mapping Keywords: Eating disorders; Virtual reality; Body mapping; Emotion regulation.

Professor Ulrike Schmidt Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/ulrike.schmidt

Dr Maria Livanou Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/maria.livanou

Dr Karina Allen South London & Maudsley NHS Foundation Trust and King's College London Email: [email protected]

Dr Ruth Knight Department of Psychology, York St John University

Background: Body image concerns are a key risk factor for eating disorders (EDs). The prevalence of EDs is rising, especially in young people. Prevention and early intervention are essential to reduce disease burden. Immersive virtual reality (VR) programmes are increasingly being explored as potential preventative or treatment interventions for EDs. Soulpaint is a novel VR platform that has translated an arts-based intervention, body mapping, into a novel VR format. Body mapping has been used as a tool to facilitate emotion regulation, reduce body dissatisfaction and increase body acceptance (Boydell, 2021).

All of this is highly relevant to EDs, where maladaptive emotion regulation, high body dissatisfaction and low body acceptance go hand in hand. Improvements in emotion regulation and body acceptance are key factors in ED recovery.

Novelty and importance: The approach taken is highly novel and has great potential for prevention and treatment in EDs.

Primary aims: To assess the feasibility and acceptability of virtual body mapping via Soulpaint as a potential (a) single session prevention for young people with body dissatisfaction and (b) adjunct to the treatment of EDs.

Study design and sample size: This PhD will include a feasibility RCT testing a single session of Soulpaint Body Mapping vs waiting list control in ~80 young people with high body dissatisfaction, to assess uptake and acceptability and effects on body image, a range of other psychosocial outcomes and food consumption.

A second project will include intensive PPI work to develop the Soulpaint prototype further for ED patients with different body sizes (underweight to obese), using a 3-4 session format and trialing the adapted intervention(s) in a clinical cohort of ~60-80 ED patients across the weight spectrum, assessing BMI, ED symptoms, body image, and other psychopathology. Qualitative interviews will be conducted.

Planned research methods and training provided: Multi-method project including quantitative and qualitative methods.

Familiarisation with/training in VR methodologies, training in conduct and analysis of clinical trials and qualitative methodologies.
Writing a systematic review, e.g body mapping in psychiatric disorders.
PPI focus groups with different ED patient populations to develop the Soulpaint prototype further.
Writing study protocols & obtaining regulatory approvals.

Year 2: Participant recruitment and conduct of the proposed studies.

Year 3: Completing participant follow-ups and writing up.

Other notable aspects of the project: This is a unique opportunity for a creative student to assist with prototype development of the VR intervention.

Publication 1: Treasure J, Duarte TA, Schmidt U. Eating disorders. Lancet. 2020 Mar 14; 395(10227):899-911. doi: 10.1016/S0140-6736(20)30059-3. PMID: 32171414.

Publication 2: Oldershaw A, Lavender T, Sallis H, Stahl D, Schmidt U. Emotion generation and regulation in anorexia nervosa: a systematic review and meta-analysis of self-report data. Clin Psychol Rev. 2015 Jul;39:83-95. doi:10.1016/j.cpr.2015.04.005. Epub 2015 May 2. PMID: 26043394.

Digital Therapies

CO24-006: Exploring the anxiolytic effects of cannabis based medicinal products (CBMPs) Keywords: Cannabinoid; Anxiety; Cannabidiol; CBD; THC.

Dr Will Lawn Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/will.lawn

Dr James Rucker Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/james-rucker

Background: The anxiolytic effects of cannabis based medicinal products (CBMPs) have been touted for decades. Medical cannabis was legalised in the UK in November 2018 and observational, prospective studies of private prescriptions have demonstrated that patients taking CBMPs show significant reductions in anxiety. CBMPs vary in cannabinoid content, including their cannabidiol (CBD) & delta-9-tetrahydrocannabinol (THC) content and formulation (e.g. oil, oral capsule, vaporised flower). There is promising evidence that CBD may reduce anxiety following a single dose in laboratory-models and following four weeks of daily treatment. However, more research is needed to unpack the anxiolytic effects of varying doses of CBD and THC. Furthermore, research into CBMP’s benefits as adjunctive treatments and in those with treatment-resistant anxiety is needed.

Novelty and importance: No controlled study has compared the effects of a single oral dose of THC and CBD on anxiety levels using an anxiety-promoting laboratory procedure in participants receiving treatment for anxiety. We need to determine the anxiolytic impact of various CBMP doses and formulations in different groups to develop future clinical trial applications.

(1) To test the acute effects of a single dose of CBD and THC on a laboratory measure of induced anxiety;

(2a) To capitalize on existing data to explore the effects of different doses of THC and CBD on laboratory measures of anxiety; (2b) and associations between CBMP usage and anxiolytic responses from real-world data in different patient groups;

(3) explore acceptability of CBMP treatment in people with treatment resistant GAD.

Study design and sample size:

Study 1: meta-analysis. Study 2: secondary data analysis of longitudinal data (n~1,000).

Study 3 (main study): non-CTIMP randomized, placebo-controlled, double-blind, crossover experiment, in people receiving treatment for GAD (n=24). ‘Study’ 4/PPI: Patient and public involvement (PPI).

Planned research methods and training provided: (1) Meta-analysis: training at KCL; (2) longitudinal analysis using linear mixed models: training by Will Lawn & KCL; (3) controlled drug administration experiments: training by Will Lawn & James Rucker.

Study 1 (Year 1): meta-analysis of CBD’s anxiolytic effects in the lab, moderated by dose; and meta-analysis of THC’s effects on anxiety, moderated by dose; systematic review of CBMP-drug interactions.

Study 2 (Year 1 & 2): mega-analysis of combined prospective, observational studies tracking CBMP patients’ anxiety levels, moderated by CBMP type and participant characteristics, specifically their concurrent medication use and treatment history. Collaboration with Sapphire & T21.

Study 3 (Years 2 & 3): a randomised, placebo-controlled, double-blind, crossover, non-CTIMP experiment comparing the one-off effects of: placebo, oral CBD (800mg), and dronabinol (oral THC, 5mg) on laboratory measures of anxiety (including a social stress test) in participants (n=24) receiving treatment for anxiety. Approvals required: KCL or NHS REC, HRA, pharmacy, KCL R&D, KCL RAC. Not MHRA. Study 4/PPI – conduct PPI to assess the feasibility of a pilot clinical trial to test a CBMP for anxiety in patients with treatment resistant anxiety.

Publication 1: Lawn, W., Trinci, K., Mokrysz, C., Borissova, A., Ofori, S., Petrilli, K., ... & Curran, H. V. (2023). The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double‐blind, placebo‐controlled, crossover experiment. Addiction, 118(7), 1282-1294.

Publication 2: Ergisi, M., Erridge, S., Harris, M., Kawka, M., Nimalan, D., Salazar, O., Rucker, J . & Sodergren, M. H. (2022). UK Medical Cannabis Registry: an analysis of clinical outcomes of medicinal cannabis therapy for generalized anxiety disorder. Expert review of clinical pharmacology, 15(4), 487-495.

Pain and Addictions

CO24-007: Development and feasibility of a novel digital intervention targeting autonomic and affective responsivity in functional neurological disorder. Keywords: Functional neurological disorder; Psychogenic non*epileptic seizures; Emotion; Autonomic; Intervention.

Professor Trudie Chalder Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/trudie.chalder

Dr Susannah Pick Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/susannah-pick

Background: Functional neurological disorder refers to a range of neurological presentations which are not explained by specific, identifiable neuropathology (APA, 2013). The disorder is associated with marked distress, disability, reduced quality of life, and poor daily functioning. Treatment options in the UK are often limited, non-specific, or non-existent, depending on geographical location.

Novelty and importance: Our experimental mechanistic studies indicate that awareness, integration and regulation of autonomic and affective responsivity might represent important treatment targets in FND. Interventions aimed at these processes have the potential to facilitate improvements in FND symptoms, emotional functioning and quality of life more broadly. However, they are currently lacking. There is a need for a readily accessible, cost-effective intervention to address these mechanisms in patients with FND, at scale.

Primary aims: This project aims to develop a novel digital intervention that will enhance patients’ understanding of the links between their autonomic/affective responses and changes in their FND and other physical symptoms, and to demonstrate the value of daily affect/arousal regulation exercises.

Specific objectives:

Obtain patient and other stakeholder views on the proposed intervention.
Develop the smartphone intervention and select a suitable wearable device.
Conduct a feasibility RCT in a sample of patients with mixed FND symptoms.

Study design and sample size: This is a mixed-methods study. Qualitative interviews and/or focus groups will be conducted with up to 20 patients with FND and other relevant stakeholders. Twenty patients with FND will be recruited to a feasibility RCT.

Planned research methods and training provided: Qualitative methods; clinical trials; experimental task design/programming. Training on these methods will be provided by the supervisors and/or members of their teams.

Systematic review of existing digital interventions in FND and other relevant clinical populations (e.g., chronic fatigue/pain).
Development of the new intervention in collaboration with relevant experts by lived experience and digital health technologies.
Obtain regulatory approvals (sponsorship, research ethics).
Feasibility RCT - Patients with FND will be randomly allocated to the active intervention or a control intervention. Outcome measures will be completed at baseline, end of treatment, and at a 3-month follow-up assessment.
Pre- and post-intervention experimental tasks (e.g., emotional reactivity/regulation, interoception).
Feasibility study and experimental task data analysis.
Completion of thesis.
Peer-reviewed journal article(s) and conference presentations.

Publication 1: Pick, S., Millman, L. M., Ward, E., Short, E., Stanton, B., Reinders, A. S., Winston, J. S., Nicholson, T. R., Edwards, M. J., Goldstein, L. H., David, A. S., Chalder, T., Hotopf, M., & Mehta, M. A. (2023). Unravelling the influence of affective stimulation on functional neurological symptoms: a pilot experiment examining potential mechanisms. J Neurol. Neurosurg. Psychiatry, jnnp-2023-332364. Advance online publication. https://doi.org/10.1136/jnnp-2023-332364

Publication 2: Yasaman Emad, Nicola Dalbeth, John Weinman, Trudie Chalder, Keith J. Petrie (2023) Can Smartphone Notifications Help With Gout Management? A Feasibility Study. The Journal of Rheumatology Nov, jrheum.2023-0711; DOI: 10.3899/jrheum.2023-0711.

CO24-008: Modulating emotion processing and its underlying neural circuitry using a pharmacological challenge in people at clinical high-risk for psychosis Keywords: Psychosis; Emotion processing; Excitation-inhibition balance; Neuroimaging; Clinical high-risk for psychosis.

Dr Gemma Modinos Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/dr-gemma-modinos

Dr Edward Chesney Department of Addictions, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/edward.4.chesney

Professor Mitul Mehta Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/mitul-mehta

Background: The development of adverse clinical outcomes in people with psychosis and people at clinical high-risk for psychosis (CHR-P) has been associated with abnormalities in a corticolimbic brain circuitry involved in how people process and regulate emotions. The basis of these abnormalities is thought to be an imbalance in excitatory (glutamatergic) and inhibitory (GABAergic) signalling between brain cells. Recent research has shown that administration of the anticonvulsant drug levetiracetam to adult rats rescued stress-induced behavioural (anxiety-like responses, impaired sociability) and neurophysiological features (increased subcortical dopamine neuron firing and hippocampal activity) relevant to psychosis. However, levetiracetam’s effect on emotion processing and its underlying neural circuitry in CHR-P individuals remains unknown. This project will address this aim by testing if levetiracetam can help improve emotion processing and resting-state functional MRI connectivity within a corticolimbic network in people at CHR-P.

Novelty and importance: This will be the first study to investigate whether acute pharmacological modulation of excitation-inhibition balance in people at CHR-P can improve emotion processing and functional connectivity of underlying brain circuitry. The results of this study may provide important proof-of-concept evidence about whether interventions that regulate emotion responsivity / excitation-inhibition balance could be a new way for understanding and treating psychosis early.

Primary aims: To determine whether the acute administration of levetiracetam normalises emotion processing in people at CHR-P, and characterise the functional connectivity of brain circuits involved in these pharmacological effects.

Study design and sample size: Basic science study that examines the effects of a single dose of levetiracetam on behavioural and neuroimaging measures. The study uses a randomised, double-blind, placebo-paired, within-subject crossover design, and will involve 36 participants who meet CHR-P criteria, to allow for potential dropout rate of 20%, aiming for at least 29 subjects with the emotion processing task and both scans complete.

Planned research methods and training provided: The neuroimaging data to be used for this independent project is being collected as part of a larger study, for which ethics application is currently being submitted to the REC. The emotion processing task will be added to the protocol for this project. Training will be provided in the clinical, cognitive/emotion processing assessments, neuropsychopharmacology, fMRI imaging methods, data analysis, dissemination.

Year 1: Ethics amendment to include emotion processing task, participant recruitment and data collection.

Year 2: Behavioural and fMRI data analysis, conference presentation, journal publications.

Year 3: Final data analysis, thesis write-up, conference presentation, journal publications.

Publication 1: Modinos G , Kempton MJ, Tognin S, et al. Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis. JAMA Psychiatry. 2020;77(2):190–200. doi:10.1001/jamapsychiatry.2019.3501

Publication 2: Burrows M, Kotoula V, Dipasquale O, Stringaris A, Mehta MA. Ketamine-induced changes in resting state connectivity, 2 h after the drug administration in patients with remitted depression . J Psychopharmacol . 2023 Aug;37(8):784-794. doi: 10.1177/02698811231189432.

CO24-009: Developing a digitally supported cognitive intervention to target intrusive images in adolescent depression. Keywords: Depression; Young people; Digital health; Cognitive therapy; Early intervention.

Dr Victoria Pile Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/victoria.pile

Professor Patrick Smith Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/patrick.smith

Dr Thomas Ward Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/thomas-ward

Background: Current interventions for adolescent depression are suboptimal and difficult to access. Intrusive images of aversive autobiographical memories (e.g. bullying) are strongly implicated in the development and maintenance of depression. Why certain images continue to haunt young people and define their sense of self is less clear. Our work suggests that a key mechanism is the young person’s inner dialogue/cognitive response to these images, e.g. self-criticism/self-compassion. We have co-developed and positively evaluated novel imagery-based protocols for young people, which are ripe for augmentation through innovative technologies. Using the AVATAR therapy approach to interacting, in real-time, with an individually tailored digital embodiment of their inner dialogue (the avatar), we will powerfully target these mechanisms and increase confidence, compassion and self-awareness.

Novelty and importance: Developing science-driven early interventions is crucial to improve effectiveness and offer young people more choice. AVATAR therapy has demonstrated large treatment effects in adults with psychosis and has recently shown promise for other disorders. It offers a powerful and engaging experiential approach that could be particularly suited to young people. A randomized controlled trial would naturally follow this project.

To evaluate the proposed cognitive mechanisms using qualitative and experimental approaches.
To co-design with young people, parents, and clinicians a novel digitally enhanced intervention targeting intrusive images.
To explore the intervention’s acceptability, feasibility, and safety.

Study design and sample size: The project would consist of robust co-design methodology (workshops and individual interviews) alongside three studies:

Qualitative study (n=10-15) exploring why certain images become intrusive and distressing.
Experimental study (two groups, n=60) assessing the mechanisms identified in study 1 (e.g., self-criticism vs. self-compassion) on future intrusions and mood.
Case series (n=10-15) to initially evaluatethe intervention in young people scoring above clinical cut-off for depression.

Planned research methods and training provided: Methods: framework analysis and semi-structured interviews; single session manipulation with ecological momentary assessment for symptom and intrusion data; case series in secondary schools.

Training: co-design principles, patient and public involvement, qualitative research, experimental design, clinical training in AVATAR and imagery approaches, statistical analysis and writing for publication, presentation skills.

Year 1: complete study 1 (ethics obtained prior to start date); KCL ethical approval for studies 2 and 3; co-design workshops with young people, parents, and clinicians.

Year 2: studies 2 and 3

Year 3: complete data collection; analysis; write-up and submission.

Dissemination: publications, conference presentations, public engagement event and conceptual video.

Publication 1: Pile V, Williamson G, Saunders A, Holmes EA, Lau JY (2021). Harnessing emotional mental imagery to reduce anxiety and depression in young people: an integrative review of progress and promise. The Lancet Psychiatry . 1;8(9):836-52.

Publication 2: Pile V, Smith P, Leamy M, Oliver A, Bennett E, Blackwell SE, Meiser-Stedman R, Stringer D, Dunn BD, Holmes EA, Lau JYF (2021). A Feasibility Randomised Controlled Trial of a Brief Early Intervention for Adolescent Depression that Targets Emotional Mental Images and Memory Specificity (IMAGINE). Behaviour Research and Therapy . 24:103876.

CO24-010: Understanding mechanisms that maintain intolerance of uncertainty in anxious people Keywords: Intolerance of uncertainty; Anxiety; Mechanism; Transdiagnostic; Digital therapeutic.

Professor Colette Hirsch Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/colette-hirsch

Dr Frances Meeten Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/frances.2.meeten.html

Background: One in six adults experience high anxiety each week, reducing their ability to work, maintain relationships and quality of life. We need more effective, scalable, interventions for anxiety. This can come in the form of a digital therapeutic delivered via mobile apps, to be used by anxious people when and where they wish. We will use the same approach we have successfully employed in the development of our other novel digital therapeutics. We will assess the causal role of candidate mechanisms that maintain a transdiagnostic process - intolerance of uncertainty (IoU) – which itself predicts and maintains anxiety. These mechanisms will form the basis of targets for a future digital intervention to reduce IoU and anxiety.

Novelty and importance: Drawing on expertise from the Experimental Psychology section of the Digital Therapeutic theme of the BRC, this research will use an evidenced based approach to understand the causal role of candidate mechanisms in the maintenance of IoU. It will then test whether an approach that targets one key mechanism or a combination of mechanism is warranted for future digital therapeutic interventions for anxious people.

Aim: To develop an understanding of the causal role of cognitive mechanisms that may maintain IoU. To then determine whether targeting a combination of mechanisms, or a single mechanism, should be considered for future digital interventions to reduce intolerance of uncertainty in anxious people.

To work with people with lived experience of IoU and anxiety with different ethnic identities to develop materials for new approaches to reduce IoU, ensuring that the materials are tailored to their day-to-day lives.
To use experimental psychology approaches to modify candidate mechanisms and assess their impact on IoU.
To determine whether a single mechanism approach or a combined mechanisms approach leads to the greatest reductions in IoU and anxiety, paving the way for new digital therapeutics.

Planned research methods and training provided: Across all stages of the PhD the student will learn a wide range of psychological research techniques including acquisition of specialist skills in experimental psychopathology, understanding of the process of new digital therapeutics development, co-design of research with people with lived experience of anxiety, using open science practices. Training via BRC Digital Therapies Theme training will be focused on a range of pertinent processes included effective intervention development, an understanding of implementation challenges, developing a sustainable model and regulatory approval processes. This will pave the way for a Post Doctoral fellowship application to develop and test a full scale digital therapeutic.

Months 1 Convene PPIE group
Month 2 Apply for KCL ethics
Month 3-4 adapt & develop materials for Study 1
Month 5-6 Programme & pilot Study 1 modification training on experimental platform in Gorilla
Month 7- 10 Run Study 1 online recruiting from across the UK via established social media routes
Study 1: Modify interpretation bias to assess its causal role in maintaining IoU.
Month 11-13 Write up Study 1 for publication
Month 12 Apply for ethics
Month 13-14 develop materials for Study 2
Month 14- 15 Programme & pilot modification training
Month 16-19 Run Study 2 via online recruiting from across the UK via established social media routes
Study 2: Modify cognitive reappraisals to assess its causal role in maintaining IoU.
Month 20-23: Write up study 2 for publication
Month 21 Apply for ethics
Month 22 develop extra materials for Study 3
Month 23-24 Programme & pilot modification training on experimental platform in Gorilla
Month 25-30 Run Study 3 via online recruiting from across the UK via established social media routes
Study 3: Investigate whether a combined mechanisms approach is superior to a single mechanism approach to reduce intolerance of uncertainty
Month 31-36 Write up PhD

Publication 1: Hirsch, C. R., Krahé, C., Whyte, J., Krzyzanowski, H., Meeten, F., Norton, S., & Mathews, A. (2021). Internet-delivered interpretation training reduces worry and anxiety in individuals with generalized anxiety disorder: A randomized controlled experiment. Journal of Consulting and Clinical Psychology, 89 (7), 575–589. https://doi.org/10.1037/ccp0000660

Publication 2: Meeten, F., Dash, S. R., Scarlet, A., & Davey, G. C. L. (2012). Investigating the effect of intolerance of uncertainty on catastrophic worrying and mood. Behaviour Research and Therapy, 50, 690-698. https://10.1016/j.brat.2012.08.003.

Precision Psychiatry

To discover better targeted treatments we exploit multimodal research data using neuroimaging, genomic, biomarker, cognitive, behavioural and remote-sensing data to identify intervention targets. This will be sustained by methodology-orientated themes to provide unparalleled breadth and depth of phenotypic characterisation across disorders.

CO24-011: Hippocampal neurogenesis: A Biomarker to predict treatment response in major depressive disorder. Keywords: Depression; Biomarker; Neurogenesis; Stem cells; Machine learning.

Professor Sandrine Thuret Department of Basic & Clinical Neurosciene, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.thuretlab.com/ & https://www.kcl.ac.uk/people/sandrine-thuret

Professor Allan Young Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/allan-young

Dr Andrea Du Preez Department of Basic & Clinical Neurosciene, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/andrea.du_preez

Background: There is a need to tailor treatment for major depressive disorder (MDD). A challenge in personalised MDD treatment is the lack of predictive biomarkers for guiding therapy selection.

Novelty and importance: One potential biomarker is hippocampal neurogenesis (HN), a well-established neurobiological process linked to MDD. However, assessing HN in live humans is impossible, which led the Thuret lab to develop an innovative in vitro HN assay using a hippocampal stem cell line and a few drops of serum from patients. Using this assay, we have endorsed HN as a biomarker for depression and have demonstrated the assay’s potential to inform treatment strategies.

Primary aims: Considering (a) the ability of the serum from patients to influence HN according to depression status and the impact of antidepressants on HN, and (b) that electroconvulsive therapy (ECT) is an efficacious MDD treatment associated with enhanced hippocampal neurogenesis, we hypothesize that positive response to ECT treatment is associated with, and potentially even driven by, HN. Therefore, the aims of this PhD project are to (1) validate the HN assay as a biomarker for predicting response to ECT treatment in MDD and (2) test an alternative biomarker - based on the same HN neurobiological evidence – that is a 10-min neurogenesis-dependent pattern separation task as part of the ongoing ECT intervention to determine low pattern separation at baseline can predict response to ECT treatment. Finally, the third aim will be to (3) optimize for clinical use the best biomarker.

Study design and sample size: Baseline serum samples (n=88-150) and pattern separation will be assessed from a planned ECT study by the Young group.

Planned research methods and training provided: The PhD student will employ and be trained for:

Hippocampal stem cell culture, immunocytochemistry, high-content cellular imaging and all the steps of the NH assay.
Administering and analysing the pattern separation Mnemonic Similarity Task (MST).
All statistical analyses and machine learning/ prediction modelling.

Objective 1: Determine how HN at baseline can predict ECT response.

Objective 2: Determine how pattern separation at baseline can predict ECT response.

Objective 3: Optimize the best biomarker.

Review existing predictive biomarkers for MDD treatment (paper1).
Generate neurogenesis data from HN assay with baseline serum.
Collect baseline MST pattern separation data.
Data analyses for HN assay and MST pattern separation.
Generation of treatment response prediction models (paper2).
Optimize best biomarker (paper3).
Thesis writing.

Publication 1: The role of circulatory systemic environment in predicting interferon-alpha-induced depression: The neurogenic process as a potential mechanism. Borsini A, Pariante CM, Zunszain PA, Hepgul N, Russell A, Zajkowska Z, Mondelli V, Thuret S . Brain Behav Immun. 2019 Oct;81:220-227. doi: 10.1016/j.bbi.2019.06.018. Epub 2019 Jun 14. PMID: 31207337

Publication 2: Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CHY, Young AH. BMJ. 2019 Mar 27;364:l1079. doi: 10.1136/bmj.l1079. PMID: 30917990

CO24-012: Using functional brain dynamics to probe transdiagnostic behavioural outcomes following very preterm birth Keywords: Functional brain dynamics; Child mental health; Psychopathology; Preterm.

Professor Chiara Nosarti Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/chiara.nosarti.html

Dr Dafnis Batalle Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/dafnis-batalle

Background: Alterations in functional brain dynamics have been associated with psychiatric disorders in adults. This project will probe functional brain dynamics in children who were born very preterm (<33 weeks’ gestation), as they experience multiple comorbid mental health concerns (Yates et al 2020) and are at increased risk of receiving a psychiatric diagnosis compared to term-born controls (25% vs 10% by the age of 18, respectively; Johnson and Wolke, 2013). Our previous work showed global atypical brain dynamics in preterm compared to term-born infants, which were associated with autism traits in toddlerhood (França et al. 2023).

Novelty and importance: Little is known about the development of functional brain dynamics following very preterm birth and whether this is linked to specific constellations of behaviors. This study will increase the current understanding of the origins of mental illness by explicating neurodevelopmental mechanisms. This novel information could be used to develop targeted interventions to reduce psychiatric risk in vulnerable children.

Primary aims: To characterize functional brain dynamics cross-sectionally and longitudinally, from term equivalent age to childhood, in relation to transdiagnostic behavioral outcomes in children who were born very preterm.

Study design and sample size: Longitudinal birth cohort study: 511 children who were born very preterm from birth up to age 11 (22 months, n=489; 4-7 years, n=251; 8-11 years, n=240 and 120 controls).

Planned research methods and training provided: We will characterize global dynamics using Kuramoto Order Parameter based measures and modular dynamics using Leading Eigenvector Analysis. To probe transdiagnostic behavioral outcomes we will use an integrative clustering approach we have previously developed (Hadaya et al. 2023): Similarity Network Fusion, combining childhood behavioral and socio-emotional measures, socio-demographic, and clinical factors. Cross-sectional and longitudinal functional brain dynamics will be compared between resultant behavioral subgroups.

The successful student will receive an unparalleled training combining knowledge about childhood neurodevelopment with neuroimaging, neuro-informatics and advanced statistics. Training will be provided both (i) directly by the project, and (ii) by wider participation in the research group. Specifically, the student will develop skills in pipeline scripting, image processing and machine learning tools. Training will be provided through attending courses on neuroanatomy, introduction to machine learning and FSL.

Year 1: Training in image processing and neuroanatomy.

Year 2: Developing different biomarkers of neurodevelopmental outcome based on features of dynamic functional connectivity, which will be validated through regression models predicting behavioral outcomes.

Year 3: The models developed in Y2 will be used to develop tailored predictions of individual outcomes. Write up time, preparation of fellowships to transition into the post-doctoral phase.

Other notable aspects of the project: Our team has extensive experience analysing paediatric neuroimaging data and training PhD candidates from diverse backgrounds. No previous experience with neuroimaging and complex data analysis is required.

Publication 1: Hadaya L, Dimitrakopoulou K, Vanes LD, Kanel D, Fenn-Moltu S, Gale-Grant O, Counsell SJ, Edwards AD, Saqi M, Batalle D, Nosarti C (2023). Parsing brain-behavior heterogeneity in very preterm born children using integrated similarity networks. Transl Psychiatry. 13(1):108

Publication 2: França LGF, Ciarrusta J, Gale-Grant O, Fenn Moltu S, Fitzgibbon S, Chew A, Falconer S, Dimitrova R, Cordero-Grande L, Price AN, Hughes E, O’Muircheartaigh J, Duff E, Tuulari JJ, Deco G, Counsell SJ, Hajnal JV, Nosarti C , Arichi A, Edwards AD, McAlonan G, Batalle D (2024). Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment. BioRxiv https://doi.org/10.1101/2022.11.16.516610 (In Press at Nature Communications #NCOMMS-23-08626B)

CO24-013: Using genetic data to improve identification of risk factors for depression Keywords: Depression; Genetics; Polygenic score; Risk prediction; Mental health.

Dr David Mark Howard Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/david.howard & https://www.drhoward.co.uk/

Dr Evangelos Vassos Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/evangelos.vassos

Background: Standard epidemiological approaches for analysing depression simply split data into those with and without the disorder and compare the risk factor profiles between the two groups. However, this assumes that everyone has the same underlying risk of developing depression. Incorporating polygenic scores, which capture the genetic liability for depression, will improve the discrimination of the non-genetic factors (such as ill health or adverse life events) associated with depression.

Novelty and importance: Depression is the leading cause of global disability with 1 in 6 people developing the disorder. The proposed research will be both impactful and novel by incorporating genetic data alongside the extensive health, medical and lifestyle data from the UK Biobank. This project will advance our understanding of the factors associated with depression and will potentially deliver clinical benefits through enabling earlier intervention and treatment.

Improve our understanding of the non-genetic risk factors associated with depression
Determine the risk factors associated with alternative definitions of depression
Identify risk factors with differential association between depression in males and depression in females

Study design and sample size: A 2x2 factorial design will be used to examine the effects of polygenic score for depression and depression status for associations with non-genetic risk factors.

Primary dataset: UK Biobank (n ≈ 500,000)
Replication dataset: Generation Scotland (n = 18,773)
Polygenic scores derived from Psychiatric Genomics Consortium data (n ≈ 3.5 million)

Planned research methods and training provided: An initial literature review will provide the student with knowledge and awareness of the subject matter. This review will help determine the non-genetic risk factors used in the research and form the basis for the student’s upgrade report at the end of year 1. Genetic and statistical analysis approaches will be used in years 2 and 3 to address the proposed research aims.

At the outset we will work with the student to create a personal development plan (PDP), identifying the skills and training required, including epidemiological and genetic methods and computer programming. The PDP will be reviewed quarterly to ensure learning and development goals are being met and that any additional training requirements are added. The student will be based in the Statistical Genetics Unit which will provide the ideal environment and level of support to undertake the research.

Year 1: Literature review; gain access to data; undertake training in genetic analysis; calculate polygenic scores for depression.

Year 2: Undertake training in epidemiology and statistical analysis; conduct analysis on depression; analyse the data using alternative measures of depression (subtypes, severity, and symptoms).

Year 3: Test for differences in risk factors by sex; write up and submit thesis.

Publication 1: https://doi.org/10.1038/s41593-018-0326-7

Publication 2: https://doi.org/10.1016/j.bpsc.2023.12.001

CO24-014: Fair and unbiased precision psychiatry: a toolkit to design accurate machine learning Keywords: Medical AI; Bias; Fairness; Precision psychiatry; Antidepressant response

Dr Raquel Iniesta Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/raquel-iniesta

Dr Nicholas Cummins Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/nicholas-cummins

Background: Treatment interventions in psychiatry are far from being effective. In depression, only 3050% of individuals achieve remission even in the context of a wellconducted clinical trial . Available research show that Artificial Intelligence (AI) makes prescribing of antidepressant drugs more accurate but the incorporation of AI has been slower than hoped given important ethical challenges like the accuracy, bias, fairness and transparency of the tools. The present PhD project will facilitate tools to guide in the design of studies that ensure a fair, unbiased and transparent development of machine learning (ML) models for antidepressant treatment selection.

Novelty and importance: The present research has a big potential to guide on the design of studies that can lead to fair and unbiased ML models building that can safely be used to personalize antidepressant treatment allocation. Current tools are designed to audit already built ML models. Our approach is to develop a toolkit that can help identify and prevent the bias/fairness/transparency problematic before the model is built: at the design stage. In addition, the research will provide insightful information on the quality of available ML models of antidepressant outcomes.

Primary aims: (1) Developing and validating a toolkit to guide in the study design that ensures the development of unbiased, fair and transparent AI to predict antidepressant treatment outcomes. (2) Assessing the study design of existing publicly available studies developing ML models to predict antidepressant response, and the resulting bias, fairness and transparency of the developed ML.

Study design and sample size: This PhD project will develop a toolkit to contribute designing studies that lead to accurate ML to predict antidepressant response and assess the performance of public ML models developed on studies of antidepressant response. Objectives / project plan: (Year 1) The candidate will run a systematic literature review to identify available ML models predictive of antidepressant outcomes. The student will create a public data base of available studies and models. (Year 2) The student will develop and validate a tool to guide on the design of unbiased, fair and transparent models for antidepressant outcomes prediction. (Year 3) The developed tool and existing ML audit tools will assess a selection of existing studies and models, including (but not be restricted to): COMED (N= 665), STAR*D (N=4041), MARS (N=604) and GENDEP (N=811).

Planned research methods and training provided: This PhD includes a training plan in ML, ethics of AI and relevant programming languages/software.

Year 1: The candidate will run a systematic literature review to identify available ML models predictive of antidepressant outcomes. The student will create a public data base of available studies and models.

Year 2: The student will develop and validate a tool to guide on the design of unbiased, fair and transparent models for antidepressant outcomes prediction.

Year 3: The developed tool and existing ML audit tools will assess a selection of existing studies and models, including (but not be restricted to): COMED (N= 665), STAR*D (N=4041), MARS (N=604) and GENDEP (N=811).

Publication 1: Iniesta R, Stahl D, McGuffin P. Machine learning, statistical learning and the future of biological research in psychiatry. Psychol Med. 2016 Sep;46(12):2455-65. doi: 10.1017/S0033291716001367

Publication 2: Iniesta R, Malki K, Maier W, Rietschel M, Mors O, Hauser J, Henigsberg N, Dernovsek MZ, Souery D, Stahl D, Dobson R, Aitchison KJ, Farmer A, Lewis CM, McGuffin P, Uher R. Combining clinical variables to optimize prediction of antidepressant treatment outcomes. J Psychiatr Res. 2016 Jul;78:94-102. doi: 10.1016/j.jpsychires.2016.03.016

CO24-015: Mood and food: exploring the relationships between depression symptoms, appetite and weight Keywords: Mental health; Depression; Eating behaviours; Genetics; Epidemiology.

Dr Moritz Herle Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/moritz-herle

Professor Cathryn Lewis Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/research/sgu

Background: Change in appetite and weight are core symptoms of depression, but we know little about their relationship and their biological underpinnings. The genetic contributions to mental health disorders and human behaviour are polygenic, with many genetic variants contributing, each having a small impact. This genetic component of disorders and behaviours can be measured in a polygenic score, giving a single number that captures genetic liability for each trait. These polygenic scores give insights into the relationship between different and their biological underpinnings.

Novelty and importance: In this PhD, you will dissect the relationship between eating behaviours, low mood, and major depression, using rich clinical, diet and mental health data from existing studies.

Primary aims: Identify the genetic and phenotypic relationships between depression symptoms, appetite and weight in a trans-diagnostic approach.

Study design and sample size: Secondary statistical analysis of existing clinical, epidemiological and genetic studies from studies such as UK Biobank, Twins Early Development study (TEDS).

Planned research methods and training provided: R statistical analysis, latent class analysis, genetic methods, polygenic scores, structural equation modelling. Training will be through online courses (DataCamp), in person training courses (e.g. Boulder genetics course), peer-to-peer learning with research team colleagues.

Year 1: Are depression symptoms associated with eating behaviours? Using data resources from TEDS and UK Biobank, you will harmonise phenotypic measures, then establish the relationships between variables, using tools such as phenotypic and genetic correlations, and polygenic scores.

Year 2: Do eating behaviours and depressive symptoms share their genetic architecture? Integrating genetics with multivariate measures of mood and eating behaviours to identify the core genetic relationships.

Year 3: What are the impacts of eating behaviours and depressive symptoms on weight change? Assessing the relationships between depression as a psychiatric disorder, eating behaviours and weight change considering mediation, interactions, and causal associations.

Other notable aspects of the project: You will be able to focus the PhD according to your interests within the BRC remit, enabling you to develop into an interdisciplinary researcher with skills in mental health, statistics, and genetics. These are skills shortage areas, with many postdoctoral research opportunities available, inside and outside academia.

Publication 1: Lewis CM, Vassos E: Polygenic Scores in Psychiatry: On the Road From Discovery to Implementation. Am. J Psychiatry. 2022. 179(11):800-806 (Review and Overview). doi: 10.1176/appi.ajp.20220795 .

Publication 2: Herle, M., Abdulkadir, M., Hübel, C., Ferreira, D. S., Bryant-Waugh, R., Loos, R. J. F., Bulik, C. M., De Stavola, B., & Micali, N. (2021). The genomics of childhood eating behaviours. Nature human behaviour , 5 (5), 625–630. https://doi.org/10.1038/s41562-020-01019-y

CO24-016: fMRI markers of cognitive decline due to Alzheimer’s disease (AD) in people with Down syndrome (DS) and its relationship with cerebral amyloid angiopathy to inform safety of anti-amyloid therapy Keywords: Down syndrome; Alzheimer's disease; fMRI; Novel biomarkers.

Professor Andre Strydom Department of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/andre.strydom

Dr Olivia Kowalczyk Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/olivia.kowalczyk & https://oliviakowalczyk.co.uk/

Background: People with Down syndrome (DS) are genetically predisposed to develop Alzheimer’s disease (AD) because of having three copies of the amyloid precursor protein gene (APP). AD is now the main health concern for older DS adults and their families. New anti-amyloid therapies hold much promise and DS is a key population in which to test the hypothesis that these therapies can prevent or delay AD. However, there are safety concerns for these treatments, including risk for brain swelling and bleeds potentially impacting on brain function, particularly in those at risk of cerebral amyloid angiopathy (CAA). It is therefore critical to have easily measured imaging markers of risk and treatment response. This project will explore features of resting-state functional connectivity in DS using fMRI, and how these relate to AD at clinical, neuroimaging, and plasma biomarker levels.

Novelty and importance: fMRI markers could help to select those suitable for early treatment of AD, and monitor response and risk. This proposal includes collaboration with an industry partner to inform future treatment trials using anti-amyloid therapies.

Aim 1: To identify fMRI correlates of DS in comparison to age and sex-matched controls, in young DS individuals before the onset of AD.

Aim 2: Determine the cross-sectional relationship between functional connectivity (measured with fMRI) and MRI markers of CAA (microbleeds, etc.), plasma Aβ auto-antibodies and AD biomarkers in older people with DS.

Aim 3: Determine the longitudinal relationship between changes in fMRI and the development of AD in older DS adults.

Study design and sample size: Longitudinal cohort study of DS adults aged 18 and older – n=60 with useable data at baseline; those >age 35 are followed longitudinally to track development of features of AD .

Planned research methods and training provided: Longitudinal cohort and neuroimaging research methods. Training in regulatory, recruitment, and data management aspects will be provided in year 1; in year 2, analysis methods and coding; year 3 - advanced fMRI analysis and writing skills.

Training (M0-5)
Data collection (follow-up data) (M6-12)
Ongoing data collection (M13-18)
Training in analysis and coding (throughout year)
Industry placement (M21-24)
Analysis of baseline data (M19-24)
Advanced MR analysis training, thesis writing etc. (M25-30)
Longitudinal data analysis (M25-32)
Complete thesis write-up (M32-M36)

Other notable aspects of the project:

Access to existing data
Existing industry collaborations

Publication 1: https://doi.org/10.1002/alz.13097

Publication 2: https://doi.org/10.1002/alz.12799

CO24-017: Towards Precision Medicine in Autism: Identifying Biomarkers of Arbaclofen Response for Sensory Difficulties Keywords: Autism; Sensory differences; Therapeutics; Arbaclofen; E/I balance.

Dr Nicolaas Puts Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/nick-puts

Dr Luke Mason Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/luke-mason

Professor Emily Jones Centre for Brain & Cognitive Development; Birkbeck, University of London

Background: Sensory difficulties are a central facet of autism, substantially impacting daily life and well-being. Emerging evidence suggests an imbalance in excitation/inhibition (E/I) as a potential source of these difficulties, leading to investigation of GABAergic modulators like arbaclofen as promising therapeutics. However, past clinical trials in ASD have faced hurdles due to both inherent heterogeneity and a focus on complex behaviours.

The link between E/I balance and sensory processing manifests more directly compared to other complex ASD features. Our prior work demonstrates that a granular approach to studying sensory processing, focusing on specific neural mechanisms like adaptation, allows for enhanced precision in understanding the E/I-behaviour relationship. Additionally, sensory processing difficulties rank as a priority area for autistic individuals and demonstrably influence other core and associated features like social interaction and anxiety. This makes the sensory system ideally suited for mechanism-based stratification in arbaclofen response studies.

We will leverage existing and ongoing studies to identify reliable neurophysiological (e.g., EEG) and behavioural (e.g., psychophysical) biomarkers of arbaclofen response within the context of sensory processing. Subsequently, we can investigate the development and variability of these biological markers in large developmental cohorts to gain deeper insights into E/I differences in autism.

Novelty and importance: Prior clinical trials in ASD have fallen short of expectations. This project adopts a novel approach by focusing on a critical area of autism – sensory processing – and employing robust experimental techniques to identify biologically-informed markers of arbaclofen response. Establishing who may or may not respond to arbaclofen is a crucial step in developing more effective interventions for individuals with ASD.

Primary aims: Our primary objective is to determine whether individual variations in E/I function, as reflected in specific biomarkers, can predict treatment response to arbaclofen for managing sensory difficulties in autism.

Study design and sample size: Multiple; We have access to data from the POND arbaclofen trial (16 weeks, autism only, pediatric, n = ~60) and arbaclofen shiftability study at KCL (placebo-controlled, two doses, case-control; n = ~50) and the proposed AIMS-2-TRIALS RCT follow-up (n = ~60), AIMS-2-TRIALS PIP and LEAP studies (developmental 3-35, n = ~600) and SFARI study (n = ~100)

Planned research methods and training provided: T

Understanding of RCT, and shiftability studies
Analysis of psychophysical and EEG data across developmental stages
Potential analysis of MRI/MRS data of E/I markers including Magnetic Resonance Spectroscopy
Advanced statistical prediction modeling and subgroup analyses
Academic writing, presentation and publication.
Transferable skills
Participatory research

Year 1: Completion of compulsory and bespoke training (e.g. GCP, GDPR, translational research); understanding of data analytical procedures and data access to various databases. Systematic review on sensory differences and E/I balance.

Year 2: Data analysis from RCT-follow-up and prediction modeling; methods chapter and first results and submission of abstract. Focus group.

Other notable aspects of the project: The primary supervisor is autistic and will also bring lived-experience to the project.

Publication 1: He, J., Oeltzschner, G., Mikkelsen, M., Deronda, A., Harris, A., & Crocetti, D. (2023). Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders. Translational Psychiatry , 11 (1). https://doi.org/10.1038/s41398-021-01525-1

Publication 2: Mason, L., Moessnang, C., Chatham, C., Ham, L., Tillmann, J., Dumas, G., Ellis, C., Leblond, C. S., Cliquet, F., Bourgeron, T., Beckmann, C., Charman, T., Oakley, B., Banaschewski, T., Meyer-Lindenberg, A., Baron-Cohen, S., Bölte, S., Buitelaar, J. K., Durston, S., … Jones, E. J. H. (2022). Stratifying the autistic phenotype using electrophysiological indices of social perception. Science Translational Medicine , 14 (658), eabf8987. https://doi.org/10.1126/scitranslmed.abf8987

CO24-018: Towards tailored treatment: Predicting real-world outcomes to first-line augmentation interventions for treatment-resistant depression Keywords: Prediction modelling; Treatment-resistant depression; Augmentation; Precision psychiatry; Treatment.

Professor Anthony Cleare Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/anthony-cleare(81cc4c4a-d4fd-4315-9426-63efa3b565ce).html

Dr Rebecca Strawbridge Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/becci.strawbridge.html

Professor Daniel Stahl Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected]

Background: Major Depressive Disorder (MDD) is considered to have the leading disability burden of all health conditions. Treatment-resistant depression (TRD) is common, severe and long-lasting, thus contributing substantially to the overall depression burdens. MDD/TRD treatments are still prescribed via trial-and-error, despite accumulating evidence that certain factors can predict response to different interventions. Although there is more evidence of response prediction for MDD than TRD, the literature is plagued by inconsistent findings. This reflects the extensive clinical heterogeneity between depressed patients. The greater severity and homogeneity of TRD illness indicate this as a high-priority focus for identifying meaningful predictors of clinical outcome. Evidence of TRD outcome prediction is so-far limited by small samples, short-term outcomes and artificial treatment settings.

Novelty and importance: We have conducted a large, long-term randomized controlled trial (RCT) of first-line TRD augmentation treatments. Unlike most RCTs, the LQD study was pragmatic in nature and therefore better reflects real-world treatment outcomes; we also followed participants up for 12months, permitting a more valid prospective assessment of clinical outcomes. Focusing on the currently recommended TRD therapies also contrasts with most existing research which assesses lesser used therapies. Finally, we emphasise employing a clinical outcome that is meaningful to patients and clinicians.

Primary aims: Our overarching aim is to develop a model comprising factors that are feasible to assess in routine practice and predict outcomes to the recommended augmenters for TRD. Specific objectives comprise:

Define a priority outcome for patients, through literature review and patient/public involvement & engagement (PPIE) consultation.
Develop a prediction model of pre-treatment factors to identify a model predicting long-term outcomes from the LQD study.
Validation of the model in other studies of emerging therapies for TRD e.g., psilocybin, ketamine.

Planned research methods and training provided: The project uses the following research methods. Additional to trans-project training (e.g., coding), we have identified high-quality training provision for each method:

1) Systematic review (objective1),

2) Qualitative research & PPIE research (objective1),

3) Prediction modelling (objective 2&3).

Year 1: Systematic review & PPIE consultation/consensus resulting in a definitive outcome variable for subsequent objectives (objective1 met). Hypothesis generation.

Year 2: Prediction model development (including model/variable selection). All data cleaning/analyses for objective2 completed. Obtain access to additional dataset(s), to observe whether the model can be applied to other novel TRD therapies.

Year 3: Data cleaning/analysis for objective3 complete. Interpretation and thesis write-up.

Publication 1: Taylor RW, Marwood L, Greer B, Strawbridge R, Cleare AJ . Predictors of response to augmentation treatment in patients with treatment-resistant depression: a systematic review. Journal of Psychopharmacology. 2019 Nov;33(11):1323-39.

Publication 2: GTaylor RW, Coleman JR, Lawrence AJ, Strawbridge R , Zahn R, Cleare AJ. Predicting clinical outcome to specialist multimodal inpatient treatment in patients with treatment resistant depression. Journal of affective disorders. 2021 Aug 1;291:188-97.

CO24-019: Using virtual reality to investigate sense of body ownership and agency in patients with functional neurological disorder and patients with schizophrenia. Keywords: Neuropsychiatry / Neurology; Functional Neurological Disorder; Psychopathology; Virtual reality; Novel therapeutics.

Dr Paul Shotbolt Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/paul.shotbolt.html

Professor Mark Edwards Department of Basic & Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/mark.j.edwards

Professor Sukhi Shergill Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected]

Background: Functional Neurological Disorder (FND) is the second commonest diagnosis in neurology clinics and causes significant disability (Carson & Stone, 2015). Motor FND symptoms are subjectively reported by patients as involuntary (Edwards, 2012). This may be mediated by altered sense of body ownership and agency, also found in schizophrenia (Shergill 2014).

Previous studies of these constructs, using experimental paradigms such as the rubber hand illusion, have led to conflicting results. In this project, novel VR environments will be used. We anticipate that their immersive nature plus the ease of manipulation to change experimental conditions will allow more valid investigation.

Novelty and importance: This project represents a novel use VR to examine key constructs in the pathophysiology of FND, specifically sense of body ownership and agency. These constructs will also be assessed in patients with schizophrenia and compared with healthy controls. Increased understanding of FND will lead to more effective treatments.

Primary aims: The hypotheses are that, compared to controls, patients with FND and schizophrenia will; 1. be more susceptible to manipulation of sense of body ownership. 2. show reduced agency over the movements of an avatar.

Study design and sample size: 25 individuals diagnosed with FND, 25 with schizophrenia and 25 healthy controls recruited. Body ownership and agency assessed in two VR environments; a ‘virtual mirror’ avatar (participants see an avatar in front of them that follows their movements), and a ‘virtual body illusion’ (participants see a projected true image of their body from the back).

Planned research methods and training provided:

Assessment of FND and schizophrenia patients
VR application design for clinical and non-clinical applications in secondment with Mesmerise
All aspects of relevant research methods and data analysis.

Year 1: Systematic review of agency / body ownership in FND and other clinical populations. Finalise design and VR environments, start recruitment.

Year 2: Run and complete study, secondment with Mesmerise.

Year 3: Write up thesis and publications, disseminate results at conferences (e.g. British Neuropsychiatry Association, UK Functional Neurological Symptoms meetings). Support for applications for post-doctoral phase. Next steps with funding – fellowships / further collaborative grants with industry sponsor (Mesmerise Global).

Publication 1: Virtual reality in functional neurological disorder: A theoretical framework and research agenda for use in the real world. David Brouwer, Hamilton Morrin, Timothy Nicholson, Devin B. Terhune, Michelle Schrijnemaekers, Mark Edwards , Jeannette Gelauff, Paul Shotbolt. https://doi.org/10.31234/osf.io/xjurc . Submitted to Lancet Neurology Dec 23.

Publication 2: Virtual reality in functional neurological disorder: A theoretical framework and research agenda for use in the real world. David Brouwer, Hamilton Morrin, Timothy Nicholson, Devin B. Terhune, Michelle Schrijnemaekers, Mark Edwards , Jeannette Gelauff, Paul Shotbolt. https://doi.org/10.31234/osf.io/xjurc . Submitted to Lancet Neurology Dec 23.

CO24-020: Innovative approaches to First Episode Psychosis: TMS-EEG and Cognition in predicting antipsychotic response. Keywords: TMS-EEG; Treatment response; First episode of psychosis; Neurophysiological biomarkers; Cognitive control.

Professor Jenny Yiend Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/jenny.yiend & http://www.csilab.org/

Dr Panayiota Michalopoulou Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: http://www.csilab.org/

Professor Sukhi Shergill Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience; Kent and Medway Medical School Website: http://www.csilab.org/

Background: Despite optimal antipsychotic treatment, 20-45% of people with psychosis continue to experience significant psychotic symptoms. Non-response occurs early in the illness and longitudinal studies in First Episode of Psychosis (FEP) have shown that over 70% of clinically classified non-responders later in the course of the illness, do not respond to antipsychotics at the time of FEP. Antipsychotic non-response is associated with more hospital admissions, poorer social functioning, and worse vocational and academic achievements. Neurobiological predictors of non-response are lacking, and its clinical identification is often delayed resulting in turn in delays in optimal treatment initiation and worse outcomes. Cognitive impairment is almost ubiquitous in FEP and has devastating effects on functioning, while antipsychotics are not effective. Cognitive control (CC) and glutamate (excitatory) and GABA (inhibitory) neurotransmission have been implicated in the response to antipsychotics.

Novelty and Importance: This is a novel application of combined brain stimulation (TMS) with electroencephalography (EEG), with inter-disciplinary cognitive neuroscience tests to investigate the role of cortical excitation and inhibition and CC in treatment response in FEP. The study will develop our understanding on pathophysiological mechanisms underlying antipsychotic response and has the potential to: a) identify neurophysiological and cognitive predictive biomarkers, which will permit the introduction of optimal treatments much earlier than currently implemented and effectively reduce the duration of untreated psychosis, which has been strongly linked with worse outcomes b) contribute to the development of preclinical models to assess efficacy of novel treatments modulating the GABA and glutamatergic systems Notably, the lack of preclinical models is often a bottleneck in drug development c) refine parameters of TMS treatments in schizophrenia.

Primary aims: We will use a safe and non-invasive combination of TMS-EEG and CC tests to detect differences in cortical excitability and inhibition between FEP responders and non-responders and study the role of CC in AP response.

Study design and sample size: We will recruit 40 FEP patients (20 responders and 20 non-responders) and 20 healthy controls in a cross-sectional design, consisting of 3 visits (screening visit, cognitive visit and TMS-EEG visit).

Planned research methods and training provided: TMS-EEG administration and TMS-EEG data analysis, highly specialised and transferable set of skills for the student to further and advance their research career.

Training in administration of cognitive tests highly specialised for cognition in psychosis and administration training in clinical scales relevant to psychosis and questionnaires relevant to neurophysiological and cognitive research in psychosis and healthy controls.

Secondment to pharma to understand commercial development of preclinical and clinical biomarkers for use in neuroscience and psychiatry and biomarker strategies in early clinical trials in psychiatric disorders.

Year 1: Training, literature revies, start recruitment.

Year 2: Continue recruitment, 6-week pharma industry secondment, preprocessing of TMS-EEG data.

Year 3: Recruitment completion, cleaning and data analysis, writing up completion and viva preparation.

Other notable aspects of the project: Unique opportunity for pharma industry secondment and experience gained on biomarker development.

Publication 1: Thomas M, Szentgyorgyi T, Vanes LD, Mouchlianitis E, Barry EF, Patel K, Wong K, Joyce D, Shergill SS . Cognitive performance in early, treatment-resistant psychosis patients: Could cognitive control play a role in persistent symptoms? Psychiatry Res 2021;295: 113607

Publication 2: di Hou M, Santoro V, Biondi A, Shergill SS , Premoli I. A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia. J Psychiatry Neurosci 2021;46: E675-701

CO24-021: Identifying a transdiagnostic biomarker of dissociative states in health and disease Keywords: Dissociation; N-methyl-D-aspartate (NMDA) receptor; EEG; Multivariate pattern classification analysis; Depersonalisation.

Dr Devin Terhune Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/devin-terhune

Dr Susannah Pick Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/susannah-pick l

Professor Mitul Mehta Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected]

Background: Dissociative states include symptoms characterised by a disruption between normally integrated systems supporting awareness and perception. Hallmark examples include depersonalisation and derealisation (feeling detached from one’s sense of self or environment, respectively). Dissociative states are increasingly recognised as transdiagnostic symptoms present in a range of conditions, including psychosis, affective disorders, and post-traumatic stress disorder. They are also associated with higher comorbidity and poorer outcomes, with significant economic impact.

The neurophysiological basis of dissociative states is poorly understood and there are no evidence-based biomarkers to aid diagnosis or guide treatment of dissociative psychopathology. Preliminary work suggests that electroencephalography (EEG) is a valuable method for identifying a biomarker of dissociation. EEG is also non-invasive and is compatible with pharmacological (nitrous oxide [N 2 O]) and psychological (mirror-gazing) methods for inducing dissociation.

Novelty and importance: This will be the first attempt to identify the shared neural markers of induced and clinical dissociative states. The research will fill a significant gap in current understanding of the neural basis of dissociation and will highlight potential transdiagnostic biomarkers of dissociation that may facilitate identification, and guide treatment, of pathological dissociation in different conditions.

Identify neural markers of induced and clinical dissociation.
Examine relevance of biomarkers to clinical outcomes.

Study design and sample size: Experiment 1 (N=40) will use a repeated-measures design examining the impact of N 2 O and mirror-gazing on dissociative states and their biomarkers in controls. Experiment 2 (N=60) will use a mixed-model design comparing these biomarkers in controls and patients with depersonalisation-derealisation disorder.

Planned research methods and training provided: The research will induce mild dissociative states using N 2 O, an NMDA receptor antagonist, and mirror-gazing in controls and patients. Our work demonstrates that these techniques are safe and well-tolerated. EEG will be recorded during resting state and dissociative symptom capture windows. Signal complexity and effective connectivity measures will be contrasted in conditions/groups and multivariate pattern classification analysis (machine learning), will be used to identify the overlapping neural features in conditions/groups. The supervisory team will provide training in induction methods and EEG application and data analysis.

Conduct a systematic review of dissociation induction methods.
Training/piloting/ethics.
Patient/public involvement.
Dissociation induction in controls.
EEG analysis.
Dissociation induction in patients and controls.
Examining predictive utility of biomarker for patient outcomes.
Research dissemination
Submit thesis.

Publication 1: Polychroni, N., Herrojo Ruiz, M., & Terhune, D. B. (2022). Introspection confidence predicts EEG decoding of self-generated thoughts and meta-awareness. Human Brain Mapping , 43 , 2311-2327. https://tinyurl.com/24hrmth5

Publication 2: Pick, S., Rojas-Aguiluz, M., Butler, M., Mulrenan, H., Nicholson, T.R., & Goldstein, L.H. (2020). Dissociation and interoception in functional neurological disorder. Cognitive Neuropsychiatry 25, 294-311. https://tinyurl.com/2e3sy554

CO24-022: Identifying prognostic markers and mechanisms underlying the development of sensory sensitivities and anxiety in children with neurodevelopmental conditions. Keywords: Precision psychiatry; Sensory processes; Autism; ADHD; Mental health.

Professor Eva Loth Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/eva.loth

Dr Jonathan O’Muircheartaigh Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/jonathanom

Dr Julie Nihouarn Sigurdardottir Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/julie.nihouarn

Background: Neurodivergent people (including autistic people and ADHDers) have 40-70% risk of developing mental health problems (anxiety, depression, burn-out). This is likely due to a combination of biological characteristics (e.g., sensory sensitivities in autism) and social/ environmental factors (e.g., bullying, stigma). Early detection, personalised treatment and prevention of mental health problems are key research and clinical priorities but hindered by a lack od well-powered studies, notably over preschool years, that assess biological and social-environmental factors.

Novelty and importance: The Preschool Brain Imaging and Behaviour Project (PIP) is the world-wide first longitudinal multi-centre, multi-disciplinary brain-imaging, “cross-condition” study of 500 preschoolers with autism, ADHD, ID or typical development followed from 3 to 6 years. PIP provides a unique opportunity to identify the interaction between social and biological markers and mechanisms that are either specific for (subpopulations within) clinical conditions or transdiagnostic.

To explore ethical, scientific and practical considerations regarding risks/ benefits of biomarkers and early interventions;
To trace developmental trajectories of emotional and sensory profiles in neurodivergent preschoolers;
To identify social (risk and protective) and biological mechanisms that are linked to concurrent clinical profiles and predict clinical development. In particular, we will test the hypothesis that processing unpredictable information impacts both sensory sensitivities and emotional processes in anxiety-vulnerability.

Study design and sample size: Longitudinal, multi-disciplinary, “cross-condition” design, with 500 children.

Planned research methods and training provided: The project involves a range of advanced quantitative methods (latent growth curve modelling, normative modelling, clustering). Training will be provided by research supervisors and/ or leading research collaborators; and workshops conducted within the AIMS-2-TRIALS and/ or Respect4Neurodevelopment networks.

Year 1: The student will conduct a survey (based on an ongoing qualitative study) on ethical, scientific and practical considerations of biomarkers and early intervention with neurodivergent participants and the general population. The student will train in growth curve analyses to identify clinical trajectories in sensory profiles and anxiety.

Years 2-3 (including 6-months secondment at Roche): The student will examine a) social risk/ protective factors and b) derive neurocognitive profiles based on the combination of brain imaging indices and behavioural tests. We will combine normative modelling of each measure with robust clustering to identify neurocognitive profiles, and then examine the relationship of neurocognitive subgroups to concurrent clinical features and their prognostic value in predicting clinical trajectories.

Other notable aspects of the project: This PhD offers multi-disciplinary training in different brain imaging and analysis techniques, participatory research, bio-ethics, and gives the student the opportunity to gain competitive industry experience through the Roche Internships for Scientific Exchange (RiSE) Programme .

Publication 1: Loth, E., et al., Identification and validation of biomarkers for autism spectrum disorders. Nat Rev Drug Discov, 2016. 15 (1): p. 70-3.

Publication 2: Loth, E., Does the current state of biomarker discovery in autism reflect the limits of reductionism in precision medicine? Suggestions for an integrative approach that considers dynamic mechanisms between brain, body, and the social environment. Front Psychiatry, 2023. 14 : p. 1085445

Translational Informatics

We use real-world data and advanced analytics capabilities to guide clinical care and public health, supported by our Informatics and Digital Therapies themes.

CO24-023: Enhancing severe mental disorders prevention through dynamic refinement of a clinical prediction model using machine learning Keywords: Precision medicine; Dynamic prediction model; Machine learning; Psychosis; Risk prediction.

Professor Daniel Stahl Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/daniel.r.stahl

Dr Dominic Oliver Institute of Psychiatry, Psychology and Neuroscience and Department of Psychiatry, University of Oxford Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/dominic-oliver

Professor Paolo Fusar-Poli Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: [email protected]

Background: Severe mental disorders (SMD) include unipolar mood disorders, bipolar mood disorders and psychotic disorders and are characterized by high clinical, societal, familial and personal burdens. To date, preventive psychiatry has focused primarily on the clinical high risk for psychosis (CHR-P) state, identifying people with prodromal psychosis, however, there is a push to extend this to SMD more broadly as transdiagnostic prevention. It is important to develop clinical prediction models (CPMs) to predict the risk of developing SMDs in individuals with mental health problems to enhance early intervention efforts. This project will focus on the development and validation of individualized CPMs for predicting SMD onset using machine-learning methods building upon a current transdiagnostic risk calculator for psychoses.

Novelty and importance: Current CPMs to predict the risk of developing psychoses are static using only potential predictors collected at the first visit to the mental health hospital. This project aims to develop a dynamic prediction model that automatically updates with the availability of new information and expands the risk predictions to other SMDs. This decision tool would allow monitoring persons at risk and offer them early intervention.

Primary aims: This project aims to transform our static first episode psychoses risk CPM into a dynamic SMD prediction model that automatically updates risk when new patient information (e.g., treatments, side effects, symptoms) becomes available using modern machine learning methods.

Study design and sample size: Electronic Health Records from Maudsley BRC CRIS system (N=1,300,000).

Planned research methods and training provided: The candidate will build a pipeline for extracting and processing patient health records to develop a dynamic machine learning prediction model for SMD risk. Two approaches will be compared: i) a statistical modelling approach (regularized cox landmark model), which is easily interpreted and performs automatic variable selection and ii) dynamic survival random forest models, which allow for the implementation of more complex models at the expense interpretability. The final model will be integrated into a web-based clinical tool, and its acceptance among clinicians and users will be assessed in a feasibility study.

The student will receive training in statistical methods, machine learning and health informatics through the Department of Biostatistics and Health Informatics' education program.

Year 1: Literature review about dynamic prediction model and early onset of psychoses, preprocessing of data, the establishment of service user group to guide planning of modelling approach and implementation.

Year 2: Development of prediction models using machine learning methods.

Year 3: Implementation into web-based application, small implementation and acceptability study, thesis write-up.

Publication 1: Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D , Stewart R, Fusar-Poli P. Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk. Schizophr Bull. 2021 Mar 16;47(2):405-414.

Publication 2: Fusar-Poli, P., Rutigliano, G., Stahl, D ., Davies, C., Bonoldi, I., Reilly, T., & McGuire, P. (2017). Development and validation of a clinically based risk calculator for the transdiagnostic prediction of psychosis. JAMA Psychiatry, 74(5), 493-500. https://doi.org/10.1001/jamapsychiatry.2017.0284.

CO24-024: Neurotypical and neurodivergent brain connectivity through the lifespan Keywords: Neurodevelopment; Autism; Brain networks; Child mental health; MRI.

Dr Luke Mason Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/luke-mason

Background: Brain structural and functional connectivity provides the basis to understand the underpinning structure and neural basis of higher-order cognitive processes and holds promise to develop stratification markers of neurodevelopmental conditions (NDCs), such as autism and attention deficit hyperactivity disorder. While some studies have shown atypical patterns of brain connectivity in adults with NDCs, little is known about the development of structural and functional connectivity from infancy to adulthood, their relation to clinical change over time (i.e., in ‘core’ neurodevelopmental features, co-occurring mental health features, and functional/quality of life outcomes) and to genetics, or what insights can be gained by the fusion of multimodal connectivity metrics.

Novelty and importance: Multi-centre consortia led by KCL, such as the AIMS-2-TRIALS and the Developing Human Connectome Project (dHCP), have acquired large multi-modal datasets of neurotypical and neurodivergent participants through the lifespan. By leveraging multimodal cross-sectional and longitudinal data, this project aims to characterise typical and atypical trajectories of brain structural and functional connectivity, and their association with genetic, demographic, and clinical measures. We will do this from infancy to adulthood, with the aim to develop stratification biomarkers for NDCs, which will accelerate the provision of mechanism-informed intervention choices to advance personalised medicine.

Characterise multimodal SC and FC (from diffusion MRI, functional MRI, and EEG) through the lifespan.
Compare patterns of SC and FC between neurotypical and neurodivergent participants, investigate concurrent and prognostic associations with both cognitive (e.g., social processing sensitivity) and clinical neurodevelopmental features, co-occurring mental health symptom severity, and quality of life.
Investigate associations between SC and FC (multimodal data fusion), and associations with polygenic scores for autism and gene expression in the brain.

Study design and sample size: We will analyse data already acquired from large cross-sectional and longitudinal cohorts. AIMS-2-TRIALS LEAP uses an accelerated longitudinal design to follow a cohort of ~700 neurotypical and neurodivergent participants between 6 and 30 years of age. The Developing Human Connectome Project includes cross-sectional multi-modal neonatal MRI (n~800), with follow-up data at 18 months.

Planned research methods and training provided: We will provide neuroimaging and data analysis training required for this project, including microstructure, tractography, and structural connectivity analyses (from diffusion MRI); fMRI and EEG analyses (e.g. RSNs, brain dynamics, microstates); graph theory; general data analysis skills (e.g. ICA/PCA); data-driven clustering; and predictive modelling (machine learning).

Year 1: Neuroimaging training, SC and FC inference. Exploration of multimodal data fusion.

Year 2: Statistical data analysis and association with neurotypical and neurodivergent development. Data-driven clusters, and association with clinical and cognitive features.

Year 3: SC-FC coupling and association with polygenic scores and gene expression. Write up time, transition into the post-doctoral phase.

Other notable aspects of the project: We have experience training PhD candidates from diverse backgrounds without previous experience in neuroimaging and complex mathematical modelling.

Publication 1: França LGS, Ciarrusta J, Gale-Grant O, Fenn-Moltu S, Fitzgibbon S, Chew A, …, & Batalle D (2024) ; Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment; Nature Communication ; In Press.

Publication 2: Mason, L ., Moessnang, C., Chatham, C., Ham, L., Tillmann, J., Dumas, G., ... & Jones, E. J. (2022) . Stratifying the autistic phenotype using electrophysiological indices of social perception. Science Translational Medicine , 14(658), eabf8987.

CO24-025: Dynamic machine learning models to capture patient outcomes at scale: leveraging routinely- and remotely-collected health data Keywords: Longitudinal; Trajectories; High-dimensional; Routine data; Dynamic.

Dr Ewan Carr Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/ewan-carr

Professor Kimberley Goldsmith Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/kimberley-goldsmith

Background: The digital transformation of healthcare is generating ever-larger amounts of high-dimensional, high-frequency, and multimodal data. This includes data from routine appointments as well as remotely collected data from smartphones and wearables.

These new data streams, combining multiple sources and addressing both physical and mental health, offer huge potential in understanding the progression and management of long-term conditions. One-third of people in the UK have multiple long-term conditions, accounting for half of hospital admissions. Long-term conditions are characterised by fluctuating symptoms, alternating between periods of remission and relapse.

Novelty and importance: Remote and routine data collection enables novel insights into outcomes among people with long-term conditions, but only if paired with appropriate statistical techniques.

This project addresses the urgent need for modern statistical approaches that make effective use of rich clinical data to build a detailed picture of symptom fluctuations during the management of long-term conditions. This includes (1) generalised additive models, a flexible approach to uncovering hidden longitudinal patterns; (2) Gaussian process modelling, a probabilistic model for complex processes; and (3) multistate models describing progression through disease states.

Primary aims: To evaluate, apply, and develop state-of-the-art statistical techniques to uncover the dynamics of patient outcomes during treatment and management of long-term conditions.

Study design and sample size: This is a secondary analysis building on two existing datasets:

RADAR-MDD (Remote assessment of disease and relapse in major depressive disorder) is the largest remote measurement study in depression conducted to date, with 623 participants providing real-time passive information (e.g., physical activity, sleep) and regular self-report assessments for two years.
IMPARTS (Integrating Mental & Physical healthcare: Research, Training & Services) provides 10 years of data on mental and physical health symptoms collected at 32 clinics across GSTT and KCH hospitals.

Planned research methods and training provided: The student will receive statistical training in joint modelling (Netherlands Institute for Health Sciences), prediction modelling (King’s College London), and prognostic modelling (University of Birmingham).

Objectives: Systematic review and simulation study comparing chosen methods.
Other activities: Data cleaning; pre-registration; methodological training.
Objectives: Application in real-world data.
Other activities: Training; presentation to patient groups.
Objectives: Publish applied studies; write thesis; apply for postdoctoral funding.
Other activities: Patient dissemination event.

Other notable aspects of the project: This project builds upon existing BRC infrastructure and provides a platform for future translation with patient-centred digital tools.

Publication 1: Skelton, Carr et al. (2022) “Trajectories of depression symptoms, anxiety symptoms and functional impairment during internet-enabled cognitive-behavioural therapy” Behaviour Research and Therapy 169. doi: 10.1016/j.brat.2023.104386

Publication 2: Matcham, Carr , et al., (2022) “Predictors of engagement with remote sensing technologies for symptom measurement in Major Depressive Disorder”. Journal of Affective Disorders 310 (1). doi: 10.1016/j.jad.2022.05.005

CO24-026: Machine learning approaches to high-dimensional mediation: explaining outcomes following psychological therapy for anxiety or depressive disorders Keywords: Mediation; High-dimensional; Moderation; Genomics; Psychological therapy.

Dr Ewan Carr Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/ewan-carr

Background: To improve patient outcomes, we must understand how interventions work (mechanisms) and for whom (subgroups). Mediation and moderation analysis can answer such questions.

The growing availability of large, multimodal datasets comprising digital phenotyping and genomics brings new opportunities but also new challenges. Existing techniques for mediation and moderation are poorly suited to high-dimensional contexts.

Recent advances combining traditional methods (e.g., structural equation modelling; SEM) with machine learning algorithms (e.g., LASSO) offer an alternative approach. These methods could be vital in early-phase studies and trials to identify novel mechanistic variables for subsequent evaluation.

Novelty and importance: Mediation and moderation can help target interventions, but traditional techniques need adapting to take advantage of new data streams. This project will apply state-of-the-art methods to uncover mechanistic variables in high-dimensional, multimodal datasets.

To deliver new insights into mechanisms underpinning interventions for anxiety and depression.
To share code and training, increasing application and translation in early phase studies.

Study design and sample size: Secondary analysis of large observational cohorts (total ~45K records, with ~27K available with genotyping information). These large datasets should provide ample power for the analyses.

The student will use:

GLAD ( G enetic L inks to D epression and A nxiety), to identify mediators/moderators of outcomes following psychological therapy. Participants with lifetime experience of anxiety or depression were recruited (~32k) with linked medical records.
TEDS ( T wins E arly D evelopment S tudy), to identify mediators/moderators of psychological outcomes in early life. Twins born 1994-1996 (~14k) completed regular assessments (ages 1-26).

Methods and training

The student will apply traditional approaches (SEM, causal mediation) alongside new machine learning methods (e.g., LASSO). They will identify potential mechanistic variables and assess the performance of competing methods.

The student will receive comprehensive training spanning traditional and modern approaches:

Causal inference and SEM (KCL).
Advanced SEM (Utrecht University).
Prediction Modelling and Introduction to R (KCL).
Clinical prediction models & Machine Learning (Maastricht University).
Objective: Systematic review of techniques for high-dimensional mediation and moderation.
Also:Data access; launch event; pre-registration; training.
Objective: Simulation study investigating statistical properties of chosen methods.
Also:Training; meet patient groups; conferences.
Objective: Apply chosen methods to identify mechanistic variables in real-world datasets.
Also:Dissemination event.

Other notable aspects of the project: This study will link exploratory machine learning techniques with confirmatory inferential approaches from causal mediation, bridging an important methodological gap.

Publication 1: Goldsmith , Hudson, Chalder, Dennison, Moss-Morris. (2020) “How and for whom does supportive adjustment to multiple sclerosis cognitive behavioural therapy work? A mediated moderation analysis” Behaviour Research and Therapy ; 128. doi: 10.1016/j.brat.2020.103594.

Publication 2: Carr et al. (2022) Trajectories of mental health among UK university staff and postgraduate students during the pandemic” Occupational and Environmental Medicine . 79 (8). doi: 0.1136/oemed-2021-108097.

CO24-027: Prediction of diagnosis, illness severity and future outcome trajectories from real world imaging data of patients with psychosis and mood disorders from the SLaM Image Bank across all ages. Keywords: MRI; Psychosis; Mood disorders; Prediction.

Dr Matthew Kempton Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/matthew-kempton

Dr Ashwin Venkataraman Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/ash.venkataraman & https://sites.google.com/view/brainregion

Background: Large-scale neuroimaging studies such as the ENIGMA consortium have established robust MRI biomarkers associated with psychosis and affective disorders. However, these findings are based on case-control samples with strict inclusion and exclusion criteria, and have not been tested in real-world clinical samples with higher comorbidities, lower resolution scanning protocols and greater ethnic diversity. If neuroimaging is to be used in clinical practice it is essential that these biomarkers show predictive validity in real-world clinical data.

Novelty and importance: For the first time, this project brings together data from the ENIGMA VBM Tool (Dr Kempton) which has recently produced detailed 3D maps brain abnormalities in a number of disorders from over 10,000 patients https://sites.google.com/view/enigmavbm ; and the SLaM Image Bank (Dr Venkataraman) which includes 13,950 MRI scans from patients from the South London and Maudsley NHS Trust https://sites.google.com/view/brainregion/slamimagebank .

To determine the diagnosis of psychosis, major depressive disorder and bipolar disorder from MRI scans of patients in the SLaM Image bank.
To determine key clinical measures such as age of onset and illness severity from MRI scans from the SLaM Image Bank.
To predict future clinical outcome in MRI scans from SLaM patients.

Study design and sample size: Predictive validity of MRI biomarkers in a real-world clinical dataset. Sample: SLaM imaging bank (n=13,950), approximately 10,000 patients from the ENIGMA consortium.

Planned research methods and training provided: Full training in neuroimaging and analysis methods will be provided by both supervisors. Dr Kempton leads a Research Methods MSc module in research methods and lectures in neuroimaging and Dr Venkataraman teaches on the Therapeutic Research in Psychiatry MSc and Clinical Neuropsychiatry MSc, students would be able to attend relevant MSc lectures as well as one-to-one training.

Year 1: Training in structural MRI analysis techniques including VBM. Selecting patients with psychosis and affective disorders from the SLaM Imaging bank, processing data with the ENIGMA VBM tool. Determining diagnosis of psychosis in the imaging bank and age of onset.

Year 2: Determining the diagnosis of Bipolar Disorder and Major Depressive Disorder from MRI scans and linking these to clinical variables. Matching up data from SLaM Image bank to outcome clinical data on CRIS.

Year 3: Predicting clinical outcome from SLaM Image Bank data. Thesis write-up.

Other notable aspects of the project: This project presents the opportunity to work with neuroimaging data from 100+ sites across the world and develop a tool to predict clinical outcome in real-world patient data across the lifespan.

Publication 1: Si S, Bi A, Yu Z, See C, Kelly S, Ambrogi S, ... Radua J, McGuire P, Thomopoulos S, Jahanshad N, Thompson PM, Barth C, Agartz I, James A, Kempton MJ Mapping gray and white matter volume abnormalities in early-onset psychosis - an ENIGMA multicenter voxel-based morphometry study. Molecular Psychiatry January 2024 DOI 10.1038/s41380-023-02343-1.

Publication 2: Venkataraman, A. V., Marshall, C. & Rittman, T. Automated brain image analysis in dementia using artificial intelligence: a roadmap for the development of clinical tools. Available at: osf.io/myuq7 . OSF Preprint. 2023.

CO24-028: Leveraging Genomic Approaches to Study Stress-Related Disorders Keywords: Anxiety; Post-traumatic stress disorder; Genomics; Statistical genetics; Prediction.

Professor Thalia Eley Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/thalia-eley

Background: Anxiety disorders and post-traumatic stress disorder (PTSD) are common, chronic, and costly. Their biology is poorly understood, and predicting their onset, prognosis, and appropriate treatment is challenging. Genome-wide association studies (GWAS) from the Psychiatric Genomics Consortium (PGC) have identified 94 (PTSD) and 59 (Anxiety) regions of the genome in which genetic variants are associated with these conditions.

Novelty and importance: Focus groups in the Twins Early Development Study (TEDS) revealed that participants want a focus on genetic influences on anxiety-related conditions and on the effect of triggering environments. This studentship will address those aims using large local datasets with rich and deep phenotype information, and leveraging our analytical networks including PGC-Anxiety and PGC-PTSD.

Aim 1: Conduct genome-wide association studies (GWAS) of anxiety in individuals with and without trauma exposure.

Aim 2: Conduct GWAS of PTSD versus anxiety in non-comorbid individuals. Collaborate with PGC-PTSD to undertake meta-analysis with other datasets and post-GWAS analyses, including prediction into local datasets.

Aim 3: Compare prediction of anxiety and PTSD from a genetics-only model versus a clinical/environmental model and versus a combined model.

Study design and sample size: We will use local datasets (Genetics Links to Anxiety and Depression [GLAD] study, TEDS), UK Biobank, and the emerging Our Future Health study. International datasets from the PGC (including PGC-PTSD, and PGC-Anxiety) will also be available. These are the largest collections of genomic data for these conditions and were sufficiently powered to identify tens of associated genomic regions.

The main methods will be GWAS and secondary analyses using genome-wide genotype data. The student will audit a MSc-level statistical genetics module, with advanced training in these areas from Dr Coleman. The student will join the local statistical genomics community, including the supervisors’ groups as well as those of Profs Lewis and Breen. Training in specific advanced skills such as prediction modelling can be obtained through the wider IoPPN, or through external courses.

Dr Coleman is a statistical geneticist with extensive experience in the genomics of stress-related disorders. He is a key analytical contributor to the PGC-PTSD and to other PGC groups.

Prof Eley is an internationally renowned expert in the behavioural genetics of anxiety. She is principal investigator of TEDS, and co-leads both GLAD and PGC-Anxiety.

Year 1: Training in GWAS methodology; begin aim 1.

Year 2: Complete aim 1. Conduct aim 2. Begin aim 3.

Year 3: Complete aim 3. Write thesis.

Other notable aspects of the project: Working with PGC-PTSD and PGC-Anxiety at the cutting-edge of genomics in these disorders will provide considerable opportunities for networking and international exposure.

Publication 1: Mundy, J., Hübel, C., Gelernter, J., Levey, D., Murray, R. M., Skelton, M., ... & Coleman, J. R. I. (2022). Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. Psychological medicine , 52 (16), 3975-3984.

Publication 2: Purves, K. L., Coleman, J. R., Meier, S. M., Rayner, C., Davis, K. A., Cheesman, R., ... & Eley, T. C. (2020). A major role for common genetic variation in anxiety disorders. Molecular psychiatry , 25 (12), 3292-3303.

CO24-029: ADHD transition: using remote technology to identify targets for intervention Keywords: Attention deficit hyperactivity disorder; ADHD; Remote monitoring; mHealth; Remote measurement technology.

Professor Jonna Kuntsi Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: http://www.kcl.ac.uk/people/jonna-kuntsi

Dr Ewan Carr Department of Biostatistics & Health Informatic, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/ewan.carr

Professor Richard Dobson Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/richard.j.dobson

Background: Late adolescence and the transition to adulthood is a highly challenging and potentially critical period for young people with ADHD that can lay the foundations for diverging adulthood trajectories. Many of the conditions that frequently co-occur with ADHD emerge in adolescence and major life transitions lead to multiple new demands and changes in available support networks. This vulnerable phase coincides with the clinical transition from child and adolescent mental health care to adult services, which itself is a focus of major current clinical concern: most youth with ADHD do not successfully transfer to adult services, despite significant needs for ongoing treatment. Opportunities for intervention are currently not fully realised due to both the young people’s disengagement from clinical services and our limited understanding of real-world targets for more holistic interventions.

Novelty and importance: Using remote measurement technology (RMT) the team has developed for ADHD, the ADHD transition project aims to identify fluctuations in symptoms and the wider phenotype at a level of detail not previously possible, and to identify real-world targets for intervention that include environmental factors and health behaviours. The study data will subsequently inform the development of an app that aims to transform monitoring, self-management, personalised treatment and engagement with clinical services during ADHD transition.

Aim 1: To identify, with precision, the nature and timing of real-world changes that take place in the transition to adulthood for young people with ADHD (e.g. changes in clinical symptoms and functional impairment; healthy lifestyle behaviours (physical activity, sleep, daily structure, online lifestyle), social support, employment/studies).

Aim 2: Using the rich remote monitoring data to identify factors that predict such changes in the outcome measures.

Study design and sample size: ART-transition is a prospective observational cohort study that involves remote monitoring of 250 young people with ADHD for up to 24 months.

Planned research methods and training provided: The student will have an opportunity to analyse data during the ‘Discover’ phase of development of a prototype for a new ADHD-transition app. This involves addressing the above aims using the available data, which will inform the subsequent prototype app development by the team. Training will be provided by the supervisors and via specialised training courses in appropriate analysis methods.

Year 1 will involve training in analytical approaches; literature review; development of analysis pipelines and preliminary analyses on data collected using the wearable device.

Year 2 will involve analyses on both active (e.g. Active App questionnaires) and passive (wearable device and Passive App) monitoring data to address research questions that form Aim 1.

Year 3 will involve analyses of both active and passive monitoring data to address research questions that form Aim 2.

Publication 1: Denyer H, Ramos-Quiroga JA, Folarin A, Ramos C, Nemeth P, Bilbow A, Woodward E, Whitwell S, Müller-Sedgwick U, Larsson H, Dobson RJ, Kuntsi J. ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol. BMC Psychiatry. 2022 Dec 20;22(1):813. doi: 10.1186/s12888-022-04429-6. PMID: 36539756; PMCID: PMC9764531.

Publication 2: Denyer H, Deng Q, Adanijo A, Asherson P, Bilbow A, Folarin A, Groom MJ, Hollis C, Wykes T, Dobson RJ, Kuntsi J, Simblett S. Barriers to and Facilitators of Using Remote Measurement Technology in the Long-Term Monitoring of Individuals With ADHD: Interview Study. JMIR Form Res. 2023 Jun 30;7:e44126. doi: 10.2196/44126. PMID: 37389932; PMCID: PMC10365629.

CO24-030: Developing and applying novel propensity scoring approaches for target trial emulations using electronic health records (EHRs) Keywords: Trial emulation framework; Target trial; Propensity scoring methods; Psychosis; Polypharmacy.

Professor Sabine Landau Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/sabine.landau & https://www.kcl.ac.uk/people/sabine-landau

Dr Giouliana Kadra-Scalzo Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/dr-giouliana-kadra-scalzo & https://kclpure.kcl.ac.uk/portal/en/persons/giouliana.kadra

Professor Robert Stewart Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/robert.stewart

Background: Routinely collected clinical data provide a powerful resource for evaluating interventions for real-world patient populations because they are large, naturalistic resources; however, internal validity is frequently impacted by confounding. Hernan and colleagues have proposed a trial emulation framework which applies causal inference concepts to mimic a target trial using observational data. In this context propensity scoring approaches are often used to handle multiple measured confounders.

Novelty and importance:

To provide clarity and guidance on using propensity scoring for trial emulation with observational data.
To develop a tool that can be applied across different types of EHR data, advancing methodological capability and supporting decision-making for trial emulations.
To develop a decision support tool for principled propensity scoring in target trial emulation using EHRs.
To develop software tools to enable propensity scoring in practice, e.g. create wrappers to convert software output into clinically meaningful effect size estimates.
To develop exemplar target trial emulation studies using the Maudsley’s CRIS EHR data resource.

Study design and sample size: In Year 1 the student will conduct a review of propensity scoring methods for trial emulation studies and relevant software. In Year 2 and 3 the student will use retrospective cohort design for Case study 1 and 2.

Based on previous work we have done, using CRIS, we will be able to access the deidentified clinical records of over 10,000 service user with a mental health diagnosis.

Planned research methods and training provided: The Maudsley’s Clinical Record Interactive Search (CRIS) platform has supported extensive research since 2008 by allowing research access to de-identified mental health EHRs on over 500,000 cases from a diverse south London geographic catchment of 1.3m residents. The student will have an unique opportunity to develop applied data science skills using an internationally leading resource. Case studies might include antipsychotic polypharmacy and/or lithium discontinuation in late life, but these will be informed by both a review and patient/carer input.

Review of propensity scoring methods for trial emulation studies and relevant software.
Seek patient/carer input on case studies for application.
Develop pipeline for extraction of relevant data for case studies.
Undertake relevant training (CRIS system; Introduction to Target Trial Emulation; Causal Modelling and Evaluation).
Develop a decision support tool to guide propensity scoring applications using EHRs.
Develop software tools (wrappers) to facilitate underdeveloped steps in the propensity scoring process.
Case Study 1 (e.g., polypharmacy versus monotherapy in the treatment of psychosis on mental health service use, general hospitalisation, mortality)
Case Study 2 (e.g., late-life lithium discontinuation in bipolar disorder on relapse).

Other notable aspects of the project: The student will work at the forefront of the exciting new field of target trial emulations using routinely collected data.

Publication 1: Scola G., Chis-Ster A., Bean D., Pareek N., Emsley E. & Landau S. (2023) Implementation of the trial emulation approach in medical research: a scoping review, BMC Medical Research Methodology 23: 186; DOI: 10.1186/s12874-023-02000-9

Publication 2: Kadra G , Stewart R , Shetty H, MacCabe JH, Chang CK, Kesserwani J, et al . (2017) Antipsychotic polypharmacy prescribing and risk of hospital readmission. Psychopharmacology 235 : 281–289. DOI: 10.1007/s00213-017-4767-6

CO24-031: Dissecting the Epigenetic and Rare Genetic Variant Basis of Eating Disorders in EDGI-UK using Nanopore DNA Sequencing Data Keywords: Eating disorders; Epigenetics; Nanopore sequencing; Rare variants; Biomarkers.

Dr Chloe Wong Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/chloe-wong

Background: Eating disorders (ED) affect ~8% of the global population (Galmiche et al., 2019) . ED are often chronic and cause substantial costs. EDs are complex with both genetic and environmental causes. Recent efforts have identified eight genome-wide significant loci to date (Watson et al., 2019) and multiple environmental factors (Larsen et al., 2021) . Epigenetics, biological mechanisms that underlies the interaction between genes and the environment, might play significant roles in the aetiology and manifestation of ED, but are understudied (Hübel et al., 2019). To address this research gap, we propose to study the epigenetic and rare genetic variants basis of ED using nanopore long read DNA sequencing data in 4,000 participants from the Eating Disorders Genetics Initiative United Kingdom UK dataset (EDGI UK; edgiuk.org ), recently funded by NIHR (a £4 million grant). The project will be supervised by Dr Chloe Wong, an expert in epigenetics and methods, and Prof Breen, an international psychiatric genetics expert and chief investigator of EDGI UK.

Novelty and importance: This will be, by 50 times, the largest epigenetic study (i.e. differential DNA methylation) and rare variant study across multiple types of ED disorder diagnoses.

Primary aims: The overarching aim of this project is to identify differential epigenetic, i.e. DNA methylation, and rare variant signatures associated with different types of Eating Disorders and related phenotypes using long read Nanopore sequencing data from 4000 ED cases from EDGI-UK volunteers and >10,000 healthy volunteers.

Planned research methods and training provided: DNA long read genome wide sequencing and epigenome-wide DNA methylation data will be generated by the BRC BioResource lab technicians and data processing plus QC will be performed using established pipelines in R. Relevant data analyses training will be provided by the first and second supervisors’ teams.

The team has extensive links with ED charities and Lived Experience; you will also work with them, co-producing the research wherever possible, as part of ongoing participant and public engagement for EDGI UK research.

Year 1: The student will familarise with the genetics and epigenetics basis of ED and EDGI database. Nanopore DNA methylation and rare variant sequencing data of 4000 EDGI participants will be generated by the BRC BioResource team at the SGDP, IoPPN. The student will be involved in performing fundamental data processing and QC, and pipeline establishment.

Year 2: Conduct an epigenome-wide association study (EWAS) to detect epigenetic signatures of eating disorders and extreme eating behaviours.

Year 3: Conduct rare genetic variant association study to detect structural variants (CNVs), repeats, and point mutations associated with extreme anorexia nervosa or binge eating disorder.

Other notable aspects of the project: We have unique involvement of people with lived experience in our eating disorders project and the student will have the opportunity to present their work to people with experience of an ED, their families, and to clinicians, as well as the research community.

Publication 1: Alameda, L., Trotta, G., Quigley, H., Rodriguez, V., Gadelrab, R., Dwir, D., Dempster, E., Wong, C. C. Y.*, & Forti, M. D.* (2022) *Joint senior authorships; Can epigenetics shine a light on the biological pathways underlying major mental disorders? Psychological Medicine , 52 (9), 1645-1665. https://doi.org/10.1017/S0033291721005559

Publication 2: Monssen D, Davies HL, Kakar S, Bristow S, Curzons SCB, Davies MR, Kelly EJ, Ahmad Z, Bradley JR, Bright S, Coleman JRI, Glen K, Hotopf M, Ter Kuile AR, Malouf CM, Kalsi G, Kingston N, McAtarsney-Kovacs M, Mundy J, Peel AJ, Palmos AB, Rogers HC, Skelton M, Adey BN, Lee SH, Virgo H, Quinn T, Price T, Zvrskovec J, Eley TC, Treasure J, Hübel C, Breen G. (2023) The United Kingdom Eating Disorders Genetics Initiative. Int J Eat Disord. doi: 10.1002/eat.24037. Epub ahead of print. PMID: 37584261.

CO24-032: Suicidal behaviour: An investigation of online temporal trends and electronic health records Keywords: Suicide; Social media; Electronic health records; CRIS; Google searches.

Dr Mariana Pinto da Costa Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/mariana.pintodacosta.html

Dr Rina Dutta Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/rina.dutta.html

Background: Coinciding with growing internet and social media use, rates of suicide, attempted suicide, and self-harm have increased.

Novelty and importance: Bringing together data from Google, social media, and electronic health records (EHRs) to investigate the relationship between searches and mentions of suicidal terminology in online platforms, and real-world adverse outcomes.

Primary aims: To investigate the temporal relationships between searches and tweets that focus on suicidal-related behaviour, and outcome fluctuations in a large mental health service covering an urban catchment area.

Umbrella review will be conducted to synthesise the global impact of online content relating to suicide-related terms on suicide-related outcomes. Pubmed, Scopus, Cochrane, Web of Science and PsycNet Databases will be screened for systematic reviews and meta-analyses.
Google Trends searches will be conducted for suicide-related behaviour terms. A downloadable datasheet of the relative search volumes will be extracted for each term.
Twitter data that refer to suicide-related behaviour will be analysed. All public tweets that include the selected keywords will be collated. The tweet text, the date and international timestamp of when it was published, and the number of retweets and likes generated will be extracted.
Natural language processing (NLP) will be used to identify suicidality-related concepts in EHRs of patients accessing secondary mental healthcare services using CRIS. Crisis admissions, and suicidality-related occurrences of patients with any clinical diagnosis that are in contact with SLAM will be studied.

This PhD project will provide a broad range of training opportunities in the: 1) conduct of an umbrella review, 2) extraction and management of big data, 3) techniques for natural language processing applied to health records data, 4) statistical skills and data analysis, 5) patient and public involvement and engagement.

Year 1: Umbrella review.

Year 2: Analysis of Google Trends searches / Twitter data / CRIS data.

Year 3: Thesis preparation/ findings dissemination and publications.

This project will start with investigating general associations between Google Searches, Twitter data and EHRs, to then focus on more specific exposure-outcome relationships. For example, if suicide-related discussions in people with depression are associated particularly with outcomes in people with that diagnosis.

The analysis strategies established in previous research using Google Trends searches, Twitter and EHRs data by our group will be followed (Kolliakou et al 2016, 2020; Dutta et al 2021; de la Rosa et al 2022).

Publication 1: de la Rosa P, … Pinto da Costa M et al. Associations of lockdown stringency and duration with Google searches for mental health terms during the COVID-19 pandemic: A nine-country study, Journal of Psychiatric Research , Volume 150, 2022, Pages 237-245, ISSN 0022-3956, https://doi.org/10.1016/j.jpsychires.2022.03.026.

Publication 2: Kolliakou A, Bakolis I, Chandran D, Derczynski L, Werbeloff N, Osborn DPJ, Bontcheva K, Stewart R . Mental health-related conversations on social media and crisis episodes: a time-series regression analysis. Scientific Reports 2020; 10: 1342.

Whole Person Care

We seek to improve physical health outcomes in psychiatric disorders and mental health outcomes in physical disorders, to address the considerable excess mortality in psychiatric disorders and the impact of mental ill-health on physical health outcomes.

CO24-033: Inequalities in HIV and Severe Mental Illness Keywords: Psychosis; HIV; Big data; Inequalities; Mental health.

Dr Margaret Heslin Department of Health Service & Population Research, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/margaret.heslin

Background: Health inequalities are avoidable, systematic disparities in health between different groups of people. Severe mental illness (long term and debilitating mental illness requiring secondary mental health care) is both a risk factor for, and an outcome of health inequalities, in that different groups of people have unequal risk of experiencing severe mental illness, and people with severe mental illness are more likely to experience inequalities in physical health. HIV is also an illness with health inequalities with unequal risk and unequal outcomes for different groups of people. However, there is very little research exploring HIV in people with severe mental illness.

Novelty and importance: No study has examined the health inequalities in HIV for people with severe mental illness. This study will be the first. Identifying health inequalities are important for highlighting need, and then making changes in policy and clinical approaches to address that need, and to inform future interventions to improve health.

Primary aims: To explore inequalities in HIV in people with severe mental illness in a UK population.

Study design and sample size: TRetrospective cohort study and retrospective case control study. People with HIV+SMI = n4,481; people with SMI only = n176,696; people with HIV only = n6,601

Evidence synthesis (MSc module)
Big data (MSc module)
Advanced statistics (MSc module)
DataCamp training for R, SQL, Python
Practical training in the use of big data from UK Health Security Agency and Biomedical Research Centre, KCL
General research skills training (informed consent, clinical research)
Transferrable skills courses (including project management, writing training, presenting skills)
Regular PhD seminars

Year 1: Orientation to university, school, department. Collaboration building with PPI groups, relevant academics, UKHSA and fellow students. Training. Conduct systematic review on risk and outcomes for HIV in people with severe mental illness. Familiarisation with data/data systems at KCL/UKHSA.

Year 2: Use data to examine inequalities in the risk of HIV in people with severe mental illness, and inequalities in the HIV treatment cascade for people with severe mental illness compared to people without severe mental illness. Identify particular points at which inequalities arise in order to inform novel future interventions.

Year 3: Collaborate with PPI groups and relevant collaborators to interpret findings, write up thesis, disseminate to researchers, clinicians, practitioners, and policy makers, through publications in academic journals, presentation at conferences, stakeholder events, education and training, and social media.

Publication 1: Heslin M et al. & Stewart R. Prevalence of HIV in mental health service users: a retrospective cohort study. BMJ open. 2023 Apr 1;13(4):e067337.

Publication 2: Brown et al & Heslin. In submission. Barriers and Facilitators to Accessing Sexual and Reproductive Health Services for People with Severe Mental Illness: A Systematic Review.

CO24-034: Using real-world evidence to emulate the cost-effectiveness of different treatment sequences of antipsychotic medication Keywords: Schizophrenia; Antipsychotic medication; Adverse event; Economic model; Cost-effectiveness analysis.

Dr Huajie Jin Department of Health Service & Population Research, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/huajie-jin

Professor Sarah Byford Department of Health Service & Population Research, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/sarah-byford & https://www.kcl.ac.uk/research/khe

Background: The schizophrenia whole disease model (WDM) developed by the applicants (HJ and SB) is the first health economic model which covers the entire schizophrenia care pathway in the UK, including prevention, diagnosis, and first-line and subsequent lines of treatment [4, 5]. However, due to a lack of RCT assessing different treatment sequences of antipsychotic medication, the effectiveness and safety data of subsequent lines of antipsychotic medications used in the WDM were obtained from network meta-analysis conducted for ‘general’ population with schizophrenia, rather than schizophrenia patients who have failed one or more different antipsychotic medications [6]. To address this limitation, we plan to use the real-world evidence (RWE) included in the Clinical Record Interactive Search (CRIS) to derive the health and cost impacts of different treatment sequences of antipsychotic medications and update the WDM.

Novelty and importance: To our knowledge, our study will be one of the first studies to use RWE to estimate the health and cost impacts of different antipsychotic sequence in people with schizophrenia. Our findings can help to improve the outcomes for people with schizophrenia by optimising the treatment sequence of antipsychotic medications and minimise the risk/severity of adverse effects.

Primary aims: To use the CRIS database to estimate the health and cost impacts of different treatment sequences of antipsychotic medication and use the derived data to update the schizophrenia WDM.

Study design and sample size: Cost-effectiveness analysis based on economic modelling. The sample size could range from a couple of hundred to a couple of thousand, depending on the number of patients in the CRIS database who meet the inclusion criteria for the decision question of interest.

Planned research methods and training provided: A protocol will be drafted for the design and analysis of RWE emulation, including the detailed inclusion/exclusion criteria and outcome measures. The following data will be extracted from CRIS for the included patients: age, sex, ethnicity, comorbidities, treatment sequence of antipsychotic medication, history of relapse, and use of healthcare services. Treatment effectiveness, safety and cost will be estimated in the propensity score-matched cohorts using Cox regression, and then used to update the schizophrenia WDM.

The student will receive training about how to (i) use the CRIS database; (2) use RWE to emulate a clinical trial; and (3) use/adapt the schizophrenia WDM.

Year 1: Background reading, training, and apply access to CRIS.

Year 2: Use the data obtained from the CRIS database to estimate the health and cost impacts of different treatment sequence of antipsychotic medications, and then use the derived data to update the schizophrenia WDM.

Year 3: Write up of the thesis and prepare papers for publication.

Publication 1: Jin H , Tappenden P, MacCabe JH, Robinson S, Byford S . Evaluation of the cost-effectiveness of services for schizophrenia across the entire care pathway within a single whole disease model. Jama Network Open, 2020; 3(5):e205888 .

Publication 2: Jin H , Tappenden P, MacCabe JH, Robinson S, Byford S . Cost and health impacts of adherence to the NICE schizophrenia guideline recommendations. The British Journal of Psychiatry, 1-6. doi:10.1192/bjp.2020.241 , 2020.

CO24-035: Understanding the impact of cardiovascular health conditions on mental health and identify intervention targets. Keywords: Depression; Cardiovascular disease; Health psychology; Mental health; Anxiety.

Dr Helena Zavos Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/helena-zavos

Background: The overarching aim of this project is to understand the impact of cardiovascular disease and its risk factors on anxiety and depression and to identify intervention targets that sit in between them. We focus explicitly on cardiovascular diseases (CVDs) and their risk factors (including hypertension, hypercholesterolemia, and obesity) as these are the common chronic physical health conditions. Depression has consistently been associated with incident cardiovascular disease, as well as poor outcomes in established coronary heart disease and stroke.

Novelty and importance: This research will explore the impact of CVD on anxiety and depression and identify protective factors and mechanisms to improve health outcomes. Understanding social and behavioural factors which help to reduce depression and anxiety after a cardiovascular event is of importance for recovery and quality of life.

Primary aims: To explore the longitudinal relationship between mental health and CVD, and their risk factors, and identify protective mediation factors as targets for intervention development.

Study design and sample size: Data from two large scale cohort studies will be utilized: 1) the 1958 National Child Development Study; the 1970 British Cohort Study, and 2) the English Longitudinal Study of Ageing (ELSA).

Planned research methods and training provided: The student will be trained in longitudinal structural equation modelling (fixed effects, random effects and mediation), and causal inference mediation analysis.

Year 1: Understanding the needs and priorities of individuals with lived experience of CVD, anxiety and depression. Participants will consist of individuals with lived experience of CVD. We will discuss the impact of CVD on symptoms of anxiety and depression and explore possible protective factors in focus groups and 1-1 interviews. Qualitative analyses will be used to characterize core themes, which will then be used to generate specific hypotheses that can be studied using secondary data analyses of pre-existing cohort studies for the quantitative analyses in studies 2 and 3.

Year 2: Investigating impact of CVD, and their risk factors on trajectories of anxiety and depression. Using secondary data analyses, the student will investigate how metabolic health conditions (e.g. diabetes or hypertension) and onset of established CVD affect trajectories of anxiety and depression.

Year 3: Identifying social and behavioural factors (including participation, loneliness, physical activity) that reduce the impact of CVD on mental health.

Publication 1: Nas Z, Zavos HMS, Sumathipala A, Jayaweera K, Siribaddana S, Hotopf M, Rijsdijk FV. Associations Between Anxiety Symptoms and Health-Related Quality of Life: A Population-Based Twin Study in Sri Lanka. Behav Genet. 2021 Jul;51(4):394-404. doi: 10.1007/s10519-021-10051-1 .

Publication 2: Herle, M., Pickles, A., Pain, O., Viner, R., Pingault, J. B., & De Stavola, B. L. (2023). Could interventions on physical activity mitigate genomic liability for obesity? Applying the health disparity framework in genetically informed studies. European journal of epidemiology , 38 (4), 403–412. https://doi.org/10.1007/s10654-023-00980-y

CO24-036: Targeting co-occurring anxiety in autism using digital wearables and therapies. Keywords: Autism; Anxiety; Mental health; Neurodevelopment; Digital therapies.

Dr Eileen Daly Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/eileen.daly.html

Dr Bethany Oakley Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/bethany.f.oakley

Professor Emily Simonoff Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/emily.simonoff

Background: At least 50% of autistic people experience anxiety, however there are few effective, evidence-based therapies available to support them (Hollocks et al., 2019; Benevides et al., 2020). This is partly due to lack of evidence for mechanisms underpinning anxiety in autism that represent targets for intervention, and a lack of acceptable, accessible, effective autism-adapted anxiety interventions (Oakley, Loth and Murphy, 2021).

Novelty and importance: This PhD project will implement digital wearables to elucidate underpinning mechanisms for anxiety in autism and provide proof-of-concept for the use of digital therapies for anxiety that are specially designed with and for autistic people.

To identify mechanisms underpinning anxiety in autism, using digital wearable technologies.
To assess the acceptability/feasibility of digital therapies that target mechanisms identified in Aim 1.

Study design and sample size: The project includes data from two ongoing studies that involve joint working with multidisciplinary teams (academics, clinicians, lived experience experts, industry, non-profit organisations) across Europe:

The AIMS-2-TRIALS Longitudinal European Autism Project – the largest multidisciplinary study worldwide to identify variability in autism that includes >700 participants ( Development in children and adults – LEAP (aims-2-trials.eu) ).
A feasibility study of an app-based anxiety intervention for autistic people that includes 100 participants ( Study Details | Molehill Mountain Feasibility Study. | ClinicalTrials.gov ).

Planned research methods and training provided: The student will gain skills in 1+ of the following (depending on their research interests):

Systematic review, meta-analysis.
Quantitative approaches – behavioural, cognitive, physiological (heart rate variability), neurobiological (EEG, MRI), biochemical (serotonin, inflammation) and/or genetic data, and app usage data.
Qualitative approaches: semi-structured interviews, thematic analysis.
Clinical trial design.

Year 1: Systematic review/meta-analysis of research on digital wearables and therapeutics targeting anxiety in autism. Contribution to data collection/database curation for the two research projects defined above, forming the core datasets for the PhD.

Year 2: Analyses of associations between anxiety and underpinning mechanisms in the context of autism (AIMS-2-TRIALS dataset). Data are available pertaining to cognitive/behavioural and social factors, neurobiology, biochemical markers/genetics, and digital tools/wearables (e.g., sleep, autonomic function).

Analyses of the acceptability/feasibility of a novel app-based anxiety intervention for autistic people (targeting mechanisms investigated above; Molehill Mountain feasibility dataset).

Year 3: Completion of work/analyses, including write up of the thesis.

Other notable aspects of the project: The PhD will support the student in their transition to the postdoctoral phase through, for example, leading/co-leading on high impact publications, opportunities to present at national/international conferences, and translation of results to inform the design/launch of a future clinical trial (beyond the scope of this proposal).

Publication 1: Oakley B, Jones E, Crawley D, Charman T., Buitelaar J., … & Loth, E. (2020). Alexithymia in autism: cross-sectional and longitudinal associations with social-communication difficulties, anxiety and depression symptoms. Psychological Medicine. 2022;52(8):1458-1470. doi:10.1017/S0033291720003244.

Publication 2: Oakley B, Boatman C, Doswell S, Dittner A, Clarke A, Ozsivadjian A, et al. (2023) Molehill Mountain feasibility study: Protocol for a non-randomised pilot trial of a novel app-based anxiety intervention for autistic people. PLoS ONE 18(7): e0286792. https://doi.org/10.1371/journal.pone.0286792.

CO24-037: White Matter Alterations in the Reward System: A Neuroimaging Study on Huntington's Disease and on Major Depressive Disorder Keywords: Huntington's disease; Tractography; Dopaminergic pathways; Striatum; Major depressive disorder.

Dr Flavio Dell'Acqua Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/flavio.dellacqua & https://www.scopus.com/authid/detail.uri?authorId=24757840500

Dr Daniel van Wamelen Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://www.kcl.ac.uk/people/daniel-van-wamelen

Background: The reward circuit, a complex network of cortical and subcortical regions connected by white matter pathways, is affected in both Huntington's Disease (HD) and Major Depressive Disorder (MDD). Decision making in people with HD (PwHD) is impaired, with a bias towards immediate reward, overlapping with reward perceptions in people with MDD. Despite the symptom overlap, underlying neural changes in the reward system remain understudied, although common WM changes might contribute. As a clearly defined monogenic disorder, HD forms the perfect setting to validate any clinical imaging methodology related to reward systems.

Novelty and importance: The project's novelty includes the use of advanced neuroimaging methods to look at structural connectivity and microstructural data from separate studies, the iMarkHD and BIODEP studies. Utilising advanced tractography, we will create an atlas of the reward circuit’s white matter pathways and compare it across conditions to identify common pathways. This mapping will allow for a comprehensive analysis of structural and microstructural white matter integrity, enhancing our understanding of the neurobiological underpinnings of neuropsychiatric symptoms in these disorders and develop new research tool and templates for future studies.

Primary aims: 1) Produce a structural connectivity atlas of the reward system; 2) Investigate cross-sectional and longitudinal changes in the reward network in PwHD; 3) Compare white matter alterations in the reward network of individuals with HD and MDD.

Study design and sample size: We will use data from the iMarkHD study (76 PwHD from premanifest to manifest stages, 36 healthy volunteers), and the BIODEP study (130 people with MDD, 40 controls). Analyses consist of separate analysis for each condition and a comparison between conditions to elucidate shared and distinct aspects of reward system alterations.

Planned research methods and training provided: Advanced spherical deconvolution tractography and microstructure imaging methods like free-water-elimination and diffusion kurtosis imaging, will be applied to characterise reward network connectivity and microstructure changes with particular attention for cortico-striatal and mesolimbic connectivity. Analytical methods will include linear mixed models, multivariate analysis, and machine learning. Training from the NatBrainLab and courses from IOPPN will provide all the essential skills for this project.

Year 1: Focus on acquiring foundational knowledge in reward circuit neuroanatomy and neurochemistry, along with initial mapping and analysis of datasets.

Year 2: Perform cross-sectional and longitudinal analysis of PwHD.

Year 3: Comparative and multivariate analyses to identify distinct white matter changes profiles in the reward circuit across HD and MDD.

Publication 1: Dell’Acqua, F., & Tournier, J. D. (2019). Modelling white matter with spherical deconvolution: How and why? NMR in Biomedicine , 32 (4), 1–18.

Publication 2: van Wamelen, D.J., & Aziz, N.A., 2021. Hypothalamic pathology in Huntington disease. Handbook of clinical neurology, 182, 245-255.

CO24-038: Improving Brain Computer Interface technologies for sensorimotor neurofeedback in children with dystonia and dystonic cerebral palsy. Keywords: Dystonia; Cerebral palsy; Brain-Computer Interface (BCI); Electroencephalography (EEG); Neurofeedback.

Dr Antonio Valentin Huete Department of Basic & Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/antonio.valentin

Dr Verity McClelland Department of Basic & Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/verity.mcclelland

Background: Dystonia/dyskinetic cerebral palsy (DCP) are complex, severely disabling movement disorders with no cure, in which individuals suffer painful involuntary muscle contractions, twisting movements and abnormal postures. Pharmacological and invasive therapies have varying levels of effectiveness and are limited by adverse effects, so there is an urgent clinical need to develop alternative, more personalised interventions.

Movement-related modulation of the specific brain rhythm “mu” is impaired in dystonia/DCP, indicating abnormal cortical sensorimotor processing 1 . Mu modulation also occurs with motor imagery, a cognitive strategy employed to improve motor function 2 , raising the exciting possibility that enhancing mu modulation via neurofeedback could have therapeutic value in this population. EEG-based BCIs have shown emerging evidence of clinical benefit as non-invasive rehabilitation interventions in adult stroke over the last decade 3 , although research in other neurological motor disorders or in children is sparse 3 . There is a critical need for improving BCI technology, usability and accessibility so these systems can be harnessed for neurorehabilitation in paediatric patients with dystonia/DCP.

This PhD project is associated with an on-going case-control study investigating whether children with dystonia/DCP can enhance their mu modulation if provided with EEG-based neurofeedback. (Sample size: 50 patients; 40 controls. Age 5-25 years).

Primary aims: To improve the BCI technology by advancing intuitive interfaces, employing gamification and refining EEG parameters for optimal and individualised neurofeedback. Additional aims include evaluating the impact of these alterations, as well as the role of cognitive strategies, on BCI user engagement and performance. This work will contribute to the above study, facilitating subsequent development of the paradigm for future clinical trials.

Planned research methods and training provided: The candidate will receive training in recording and advanced analysis of scalp EEG, statistical analysis, scientific writing and presentation skills. They will work directly with children/young people with movement disorders and their families and will learn to deliver cognitive therapies including guided discovery and Cognitive Orientation to daily Occupational Performance.

Year 1: Training in EEG data collection/analysis; developing BCI gamification and performance measures; exploring and refining EEG parameters (e.g. peak frequency, topography, temporal characteristics); cognitive strategy training.

Year 2: Conduct EEG spectral, connectivity 4 and statistical analyses; continue refining BCI paradigm and performance measures,.

Year 3: Continue data analysis; optimise EEG parameters for personalised neurofeedback.

Collaborating with a multi-disciplinary clinical paediatric team, neurophysiologists, computational neuroscientists and biomedical engineers, both nationally and internationally.
McClelland VM, Fischer P, Foddai E, et al. EEG measures of sensorimotor processing and their development are abnormal in children with isolated dystonia and dystonic cerebral palsy. Neuroimage Clinical . 2021; doi.org/10.1016/j.nicl.2021.102569
Butchereit K, Manzini M, Polatajko HJ, Lin JP, McClelland VM, Gimeno H. Harnessing cognitive strategy use for functional problems and proposed underlying mechanisms in childhood-onset dystonia. Eur J Paediatr Neurol . 2022;41:1-7. doi:10.1016/j.ejpn.2022.08.007
Behboodi A, Lee WA, Hinchberger VS, Damiano DL. Determining optimal mobile neurofeedback methods for motor neurorehabilitation in children and adults with non-progressive neurological disorders: a scoping review. Journal of neuroengineering and rehabilitation . 2022;19(1):104. doi:10.1186/s12984-022-01081-9
Sakellariou DF, Dall'Orso S, Burdet E, Lin JP, Richardson MP, McClelland VM. Abnormal microscale neuronal connectivity triggered by a proprioceptive stimulus in dystonia. Scientific reports . 2020;10(1):20758. doi:10.1038/s41598-020-77533-w

Publication 1: McClelland VM , Fischer P, Foddai E, Dall’Orso, S, Burdet E, Brown P, Lin JP. EEG measures of sensorimotor processing and their development are abnormal in children with isolated dystonia and dystonic cerebral palsy. Neuroimage: Clinical 2021 30:102569. https://doi.org/10.1016/j.nicl.2021.102569

Publication 2: McClelland VM, Valentin A , Rey HG, Lumsden DE, Elze MC, Selway R, Alarcon G, Lin JP. Differences in globus pallidus neuronal firing rates and patterns relate to different disease biology in children with dystonia. Journal of Neurology, Neurosurgery and Psychiatry 2016; 87(9):958-67.

PExperimental Medicine and Novel Therapeutics

CO24-039: Using ultra-high field (7T) MRI in children to understand early adverse genetic and environmental influences on subcortical brain development Keywords: Epilepsy; COVID-19; Developmental neuroimaging; Ultra-high field 7T MRI; Functional and structural brain networks.

Dr Tomoki Arichi School of Biomedical Engineering and Imaging Sciences, King's College London Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/tomoki.arichi

Dr Chiara Casella Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience Email: [email protected] Website: https://kclpure.kcl.ac.uk/portal/en/persons/chiara.casella

Background: The highly choreographed program of prenatal brain development sets the stage for later life. Alterations in this process correlate with impaired cognitive and behavioural and neurological outcomes. Early adversities/insults to this process can include extrinsic factors to the fetus like [1] maternal immune activation, [2] direct viral infection of the fetus and intrinsic factors like [3] genetic or chromosomal anomalies (amongst many others). All have been associated with behavioural, cognitive or neurological neurodevelopmental conditions (NDCs). The occurrence of common NDCs with these varied risk factors may be underlined by similar abnormal development in cortical networks.

Novelty and importance: Ultra-high field (7T) MR imaging offers greatly enhanced signal to noise ratio compared to standard MRI systems, enabling acquisition of high resolution and contrast data with significantly higher sensitivity. Our ongoing 7T epilepsy study and the newly-funded Gen2020 study (focusing on children born during the initial COVID-19 pandemic) use state-of-the-art advanced imaging at 7T, offering a unique way to interrogate distinct fetal risk factors for common outcomes. Crucially, the enhanced sensitivity allows study of subcortical structures like the thalamus are highly sensitive to changes in early development (implicated in preterm birth and epilepsies for example) but the structure itself is complex, with many small nuclei connected to diverse cortical networks.

Delineate subcortical/cortical brain networks using local and publicly available 7T MRI.
Identify the influence of prenatal cortical malformations on subcortical-cortical networks.
Explore the effect of prenatal maternal infection with COVID-19 on childhood brain network development, examining associations between inflammatory markers at birth (maternal and infant) with brain outcome.

Cross sectional, cross-disorder design involving two ongoing studies: childhood focal epilepsy (n=40, collection ongoing) and Gen2020 COVID-19 (n=50, to be collected).

Planned research methods and training provided: Analysis of very high-resolution imaging data, advanced imaging statistics, data-driven and supervised methods to extract important features from neuroimaging data, Shell scripting (bash, python). Training will be provided by research supervisors, collaborators and their teams.

Year 1: MRI safety, child and adult consent and assent training. Image analysis pipeline development for thalamic network analysis.

Year 2: Collection of 7T MRI data in children with maternal COVID-19 exposure. They will investigate associations with birth inflammatory markers.

Year 3: Compare network connectivity in epilepsy and COVID-19-exposed children, correlating with developmental outcomes.

Publication 1: Casella, C., Vecchiato, K., Cromb, D., Guo, Y., Winkler, A. M., Hughes, E., ... & O’Muircheartaigh, J. (2023). Widespread, depth‐dependent cortical microstructure alterations in paediatric focal epilepsy. Epilepsia .

Publication 2: Bridgen, P., Tomi-Tricott, R., Uus, A., Cromb, D., Quirke, M., Almalbis, J., …& Arichi T. (2023). High resolution and contrast 7 Tesla MR brain imaging of the neonate. Frontiers in Radiology.

Accessibility

The NIHR Maudsley Biomedical Research Centre (BRC) is part of the NIHR and hosted by South London and Maudsley NHS Foundation Trust in partnership with King's College London . We are part of Kin g’s He alth Pa rtners Academic Health Scien ces C entre .

UCL Department of Space and Climate Physics

Solar Physics

PhD Projects 2024: Solar Physics

PhD projects in Solar Physics for our STFC studentships 2024 are listed below.

Unveiling the Sun, next generation studies of the Sun’s magnetic activity (Prof. Lucie Green)
Fast Magnetic Reconnection in Solar Flares – Preparing for Solar-C (Prof. Sarah Matthews)
The Link Between Solar Coronal Heating and Particle Acceleration (Dr. Hamish Reid)

Unveiling the Sun, next generation studies of the Sun’s magnetic activity

Primary supervisor: prof. lucie green.

The Sun's character is determined by its dynamic and evolving magnetic field, which harbours energy that is used to power some of the most violent and energetic events in the Solar System - coronal mass ejections. These ejections are of intense interest as they can drive major space weather impact at Earth, and space weather forecasters around the world seek to predict when an eruption will reach the Earth and what the degree of impact will be. For example, the changes these ejections produce in the near-Earth space environment can ultimately lead to disruptions to electricity distribution, communications, and navigation systems. Knowing why and when these ejections will occur are questions that are centrally important to not only understand how the Sun operates but also for developing an ability to make accurate space weather forecasts. However, for many decades the Sun appears to produce eruptions that are detected at Earth but which are not seen leaving the Sun’s atmosphere. These are “stealthy” events and research at MSSL has shown that they may originate from high up in the Sun’s atmosphere, at the limit of where our telescopes previously were able to collect data. That was the case until the launch of ESA’s Solar Orbiter spacecraft, which provides a new set of eyes on the Sun through the EUI telescope that images the Sun’s atmosphere using extreme ultraviolet radiation and which enables a view much larger than previously possible. In this PhD project, wide field-of-view EUV images will be used to monitor how large-scale plasma and magnetic structures evolve over time and how changes at small spatial scales are able to contribute to the large-scale evolution of the magnetic field to the point of eruption. The PhD research will employ relevant image processing techniques to identify evolutionary pathways that lead to the ejection of high-altitude coronal mass ejections. Data will be used from the Solar Orbiter mission (that was launched in 2020), in which MSSL plays a leading role, but there are opportunities to use other space-based instrumentation, such as from NASA’s Parker Solar Probe, and data from ground-based radio telescopes to provide a multi-wavelength analysis. Although based at MSSL, you will ultimately have the opportunity to work in international collaborations with our colleagues around the world to bring together the skills and knowledge needed to study the building blocks of the magnetic field that relate to coronal mass ejections and help generate knowledge that feeds into space weather forecasting.

YouTube Widget Placeholder https://www.youtube.com/watch?v=hdTKmuTLcwQ

Desired Knowledge and Skills

Undergraduate modules in plasma physics, solar physics or astrophysics
Strong computational skills including experience of programming in Python

Fast Magnetic Reconnection in Solar Flares – Preparing for Solar-C

Primary supervisor: prof. sarah matthews.

The Sun is our closest star, and with space now firmly established as part of our society’s environment, its unique proximity has inescapable consequences for us. While its radiation provides the energy source of our whole ecosystem, our understanding of how the variations in that radiation control, e.g. our climate, still contains huge gaps. As well as the long-term variations in the solar output, the Sun exhibits a cycle of activity the constituents of which are explosive events which release energy. This explosive energy release occurs on a myriad of scales, from nanoflares to huge eruptive flares, which are accompanied by the bulk eruption of plasma and magnetic field known as coronal mass ejections (CMEs) and whose impacts can be seen globally across the Sun and throughout the heliosphere. The most extreme of these events constitute the largest examples of explosive energy release within our solar system, during which upwards of 10 26 J of energy is released. Solar flares comprise a key component of space weather, and yet despite their key importance and the extensive range of observations available from space and the ground, several open questions remain. Magnetic reconnection is the primary process by which energy release occurs in solar flares with current theories predicting that this occurs in a current sheet high in the corona. While there are many observable signatures predicted by our models, observations of the site and details of reconnection process remain a challenge, particularly spectroscopic observations. However, recent advances in modelling and new techniques for indirectly inferring the conditions in the current sheet provide further opportunities for studying this process. The project will initially utilise existing spectroscopic data from the Hinode EIS, IRIS, Solar Orbiter EUI, SPICE and STIX instruments, as well as from ground-based telescopes where available to advance our understanding of the magnetic reconnection processes occurring in solar flares. As we move towards Solar Maximum the student will also have the opportunity to propose and acquire new observations The research undertaken will form part of the solar group’s preparatory work for the Solar C EUVST mission currently under development and scheduled for launch in 2028. The student undertaking this project would thus participate both in the international Hinode EIS and Solar C EUVST teams, including attending team meetings and collaborative visits.

Undergraduate or MSc degree in physics, astrophysics, or related area is desirable, but curious and motivated students with other backgrounds will also be considered.
Previous experience of data analysis, as well as good writing and presentation skills, are also desirable but not essential.

The Link Between Solar Coronal Heating and Particle Acceleration

Primary Supervisor: Dr Hamish Reid

Our Sun’s atmosphere, the solar corona, is extremely unstable. Magnetic instabilities heat the corona to 1 million degrees and occasional explosions known as solar flares accelerate particle beams to near-light speeds. The strong magnetic fields above sunspots can cause the corona to become even hotter, up to 3 million degrees. Mini solar flares can be triggered over hours or even days, continuously accelerating particles. One would naively expect the heating above active regions to be linked to the continuous particle acceleration. However, the link between the accelerated particles and the super-heated plasma above active regions has remained elusive for many years. In part due to a lack of resolution in our telescopes. The recent launch of ESA’s Solar Orbiter spacecraft has provided the closest, most detailed view of solar active regions through the Extreme Ultraviolet Imager (EUI) telescope. We can now observe many small-scale phenomena (1000 km is small on the Sun!), such as solar “campfires”, that are like mini solar flares, where the corona gets locally heated to 2 million degrees. We can also observe accelerated particles better than before using new-age radio interferometers like the Low Frequency Array (LOFAR). Radio waves are emitted by the accelerated particles as they travel through the hot corona and out through our solar system. During this PhD, we will investigate the link between the small brightening events that locally heat the corona and the radio signatures of the accelerated particles. We will analyse how both signatures evolve with time and compare the spatial extent of each signature to finally show the link between small-scale plasma heating and weak particle acceleration events. Whilst space-based and ground-based imaging will be used, there is also scope to measure these accelerated particles close to the Sun using the onboard detectors of Solar Orbiter and NASA’s Parker Solar Probe spacecraft. MSSL plays an integral part of the Solar Orbiter mission and contributed towards the construction of the EUI camera. Consequently, you will be able to work directly with the EUI team and collaborate with international scientists around the world to develop and hone your research skills. There is also the opportunity to visit one of these international teams for an extended duration. Finally, there is also the possibility of simulating the propagation of these near-relativistic particle beams using our high-performance, parallelised code, to explore how much local heating is generated as these beams travel outwards from the Sun.

Undergraduate modules in plasma physics, solar physics or astrophysics.
Strong computational skills including experience of programming in Python.

Skip to content
Study with us

We make sure that every student has a hands-on education that’s filled with adventure.

Study with us overview
Applying to university overview
Admission requirements
Application dates
Pathways to university
Undergraduate courses overview
Double degrees
A-Z listing
Postgraduate courses overview
Research degrees
Online courses
Short courses
Where study meets sustainability
Our accommodation overview
Cradle Coast
Scholarships, fees and costs overview
Domestic scholarships
International scholarships
Starting at the University overview
Accepting and enrolling
Orientation and settling in
Learning abroad
International students overview
Our agent partners

There’s more to uni than studying. Learn how you can connect with new people through events, sports, volunteering opportunities, and more.

Uni life overview
Our campuses overview
Transforming our University
Experience Tasmania
Support and wellbeing
Clubs and societies
Sport at the University
Aboriginal students - Riawunna Centre

Our research

We are proud of our research excellence, which delivers impact for and from Tasmania.

Our research overview
Research institutes and centres
Research facilities and infrastructure
Partner with us
Research stories and insights
Discover our expertise
Research support
Research degrees overview
What is a research degree?
Scholarships and fees
Available projects
Apply to become a research student

For community & partners

We pride ourselves on forming deep connections, collaborating not just with one another, but with local industry, schools, and everyone who calls our island home.

For community & partners overview
Community and public engagement
For schools overview
Subscribe for student activities updates
Aboriginal networks and resources overview
Aboriginal Business
For alumni overview
News and publications
Giving overview
Donate to the University
Donate to scholarships
Partner with us overview
Educational partnerships
Business, industry, and government partnerships
Tasmanian Policy Exchange
Arts and cultural collections

Tasmania is an island of creative and curious minds. No matter where you join us from, you’ll become part of a welcoming and collaborative community.

About us overview
Governance, leadership and strategy
Sustainability
Inclusion, diversity and equity
Public reporting
Lutruwita Aboriginal Tasmania
Our colleges and schools
Safety, security and wellbeing
News and stories
Events overview
Our Open Day events
Graduation ceremonies
Working at the University overview
Current job opportunities
Casual registration
Applying to work with us
Contact us overview
Raising concerns and complaints

How can we help you?

I'm interested in, are you an international student.

We want to provide content that's relevant to you. Your options are stored in a browser cookie which you can delete at any time via the link below.

Choose a login

Available projects for research degrees.

We offer a diverse range of higher degree research projects.

Explore our available research degree projects

Artificial Intelligence and Accounting

Carbon Literacy and Antarctic Tourism

Ocean Accounting for Governance

Agriculture

Tasmanian institute of agriculture.

3-D food printing

3-D printing valorisation of food wastes

Beating smoke taint with sparkling wine

Biological control in apple orchards

Identification of honey components

Microbes and Carbon

Natural antioxidants to maintain flavor

New Microwave Tech for Food Processing

Novel natural antioxidants for foods

Optimising netting in apple orcharding

QTL for low P tolerance in barley

Simulating soil carbon

Simulating soil waterlogging

Sustainable apple orchard nutrition

Virtual-fencing for Tasmanian dairy farms

Architecture and Design

Architecture, media and tourism

Interpretation and Heritage Architecture

Mass timber from plantation Blue Gum

Plywood from plantation Blue Gum

Towards Net Zero: Thermal, hygrothermal

UX Design for health applications

Biological Sciences

Computer Vision for Plant Hydraulics

Disease and behaviour change: Tas devils

Ecology of Tasmanian eagles

Epigenetics to understand disease

Historical landscape changes in Tasmania

Novel signals in nutrient acquisition

Post-fire vegetation resilience

Quoll translocation habitat

Reducing ecosystem flammability

Subalpine grassland futures in Tasmania

The winners and losers of disturbance

Who controls the timing of birth?

Bespoke Sustainable Metal Catalysts

Biomass Burning Tracing

Detection and Monitoring of TFA

Fibre-based electrofluidics

Methods for trace explosive detection

Nanoplastics Analysis

New catalysts for chemical synthesis

Creative Arts and Media

Crafting designs on wealth

Media Representations of Natural Disaster

Dementia Research

Wicking dementia research and education centre.

CLN3 disease: Are microglia the problem?

Culturally respectful and safe care

Dementia Respite Community of Practice

Educating the Dementia Respite Workforce

Speech and motor changes in dementia

Venturing out

Earth Sciences

Geometallurgy of Ernest Henry

Nautanen IOCG deposit characterisation

Submarine Volcanism

Economics and Finance

No projects currently available.

HE online and blended student engagement

Teacher registration transition

Engineering

Automating neonatal oxygen therapy

Debris Flows and Machine Learning

DER to support EV charging

Dynamic Degradation of Sensitive Clays

Electronic noses to assess woodsmoke

Green heating and cooling technology

Hybrid HVDC Circuit Breaker

Improving indoor environmental quality

Multiport Power Converters

Passenger vessel hull optimisation

Structural Health Monitoring of Towers

Thermal management in electric vehicles

Viscoplastic mantle convection

Geography, Planning and Spatial Sciences

An app for disaster preparedness

Climate adaptation in practice

Compound drought Southern Hemisphere

Machine learning for flood resilience

Mitigating inequity in climate collapse

Post-seismic deformation of New Zealand

Private land conservation design

Saltmarsh Restoration Ecology

Shaping university mobilities

University ground plan activation

Wellbeing impacts of climate change

Health Science

Australian Writing After Globalisation

Crimes of the Colonially Convicted

Eating at the Colonial Table

Embodied Identity and Social Justice

Problems in Greek and Roman Religion

Rhetoric, gender, and emotion in Rome

Writing Revolutionary Era British Lives

Information and Communication Technology

Adaptive Feedback Model for Learning

Chatbot with Facial Expressions

Context-Aware Adaptive Object Detection

Deep learning on infertility diagnosis

Ecoacoustics with the Internet of Things

Generative AI for Scientific datasets

Immersive Visualisation with Point Cloud

Intelligent IoT Application Scheduling

Language-Based Multi-agent Collaboration

Modeling Affective Learning Behaviours

Seabed Surveillance Using Dist. AI

Trust Aware Crowd Service Management

Antarctic Governance Futures

Antarctic Solar Radiation Management

Beyond the Consultative Parties

Developing solutions to forced migration

Ecosystem Restoration Law in Australia

Environmental market mechanisms

Nature Repair or ecological restoration

Ownership of Genomic Sequence Data

Sustainability Disclosures

Youth justice and sex offending

College of Business and Economics

Corporate volunteering

Psychological Capital in Extreme Work

Worker Exploitation in Tasmania

Australia Institute of Health Service Management

Marine and antarctic, institute for marine and antarctic studies.

Data quality from underwater imagery

Environmental remediation with oxygen

Giant crab's dietary analysis as a proxy

Habitats for fisheries

Ice shelf deep learning

Long term changes in Southern Bull Kelp

Mapping Earth's magnetism from space

Marine spatial planning in Australia

Modelling cloud-aerosol interaction

OAE feasibility in the field

Paralytic Shellfish Toxins in abalone

Southern Ocean biological pump

Water reuse implications in AGD bathing

Why do scallop beds boom-and-bust?

Australian Maritime College

Antarctic and Southern Ocean Logistics

Enhancing authenticity in pedagogies

Entrapment Tunnel Monohull Performance

Evaluating the impact of freight subsidy

Fouling Impact Assessment

Fouling Management Framework

Human Element for Blue Economy

Human Factor in Autonomous Shipping

Knowledge transfer in maritime domain

Machine learning path replanning for AUV

Manoeuvring of an underwater vehicle

Offshore Hydrogen Production with wind

Parametric roll prediction and control

Planning future seafarer recruitment

Power Hardware in Loop Test System

Reliability assessment of offshore facilities

Smart Damage Modelling System

Understanding the role of the consumer in the quest for zero-waste

Mathematics

Ecoacoustics with Machine Learning

Plumes and Fingers on Fluid Interfaces

Medical Research

Menzies institute for medical research.

Addressing high healthcare usage

Assisting working people with MS

Between self-report and proxy report in adults with intellectual disability

Development of a wild immunology toolbox

Discovery of rare cancer risk variants

Exercise for hypertension detection

Genetics of interstitial lung disease

Health economics of Parkinson's Disease

Marsupial cancer and viral immunity

Multiomics of musculoskeletal disorders

Neuroinflammation in MS

Neuroscience PhD Project

Parkinsons Disease quality of life

Return to Work after Breast Cancer

The heart health benefits of fitness

The role of EBV in multiple sclerosis

Transforming lunch provision in Tasmanian schools

Waking up quiescent neural stem cells

Birthing in lutruwita Tasmania

Cortical Hyperexcitability in ALS

Finding epigenetic codes in the brain

Haematopoiesis and the epigenome

Health Literacy Responsive Schools Tool

HealthLit4Kids: Scalable & Sustainable?

Modifying the epigenome of brain cancer

Sustaining Health Service Improvements

The Inverse Care Law in the Australian Health Care System

Carers managing wounds of the frail

Health literacy for Older People

Implementation Science improving ED care

Mental health and substance use

Mental Health First Response Course

Mental health in residential aged care

Older person's wishes in ICU

Pain and frailty in older adults

Pharmacy and Pharmacology

Preventing Drug-Related Hospitalisations

Preventive Medication Use in the Elderly

Gravitational Wave Astrophysics

Hybrid tracking of space junk

Probing cosmic gas with black hole jets

Psychological Sciences

Games & Wellbeing: Flow & need satisfaction

Learning how we learn

Social Sciences

Critical International Relations & Australia's Foreign Policy in the Asia-Pacific

Out-of-Home Care Student Attendance

Queer Identities in Antarctica

Reducing litter leakage

Rethinking the Geopolitics of Antarctica

Sociology of cosmetic technologies

Trauma-informed Policing

Our whole island is your campus

When you’re in one of the world’s most amazing places, you need to get outside, explore and live while you learn.

That’s why our courses give you the opportunity to explore nature and access adventure while you study. Field work and hands-on learning will take you all over our incredible island.

The University of Tasmania uses cookies to deliver content that’s relevant to you. We rely on cookies to remember your preferences, provide personalised content, and to analyse our website traffic. You consent to our cookies if you click “Accept”. Please refer to our privacy policy for more information.

Essential functionality (required) - these cookies are needed for this website to run and are always turned on.
Personalisation and preferences - these cookies help us remember your preferences and deliver a more personalised experience.
Personalisation and analytics - these cookies help us gather non-identifiable data about the way our site is used and to help us make improvements.
Marketing and promotion

PhD Projects 2024

Biology/Physics/Computational Science Title: Optogenetic and computational interrogation of metastable brain-states in larval zebrafish PhD supervisor (project leader): Bormuth Volker (LJP, IBPS, Paris), [email protected] Co-Supervisor: Monasson Rémi (LPENS, Paris), [email protected] Download here

Biology/Mathematics/Computational Science Title: Modeling Neurovascular and Neurometabolic Crosstalk PhD supervisor (project leader): Cauli Bruno (NPS, IBPS, Paris), [email protected] Co-Supervisor: Soula Hédi (Nutriomics, Paris), [email protected] Download here

Biology/Chemistry Title: CALVINUPGRADE – redesign enzymes to improve photosynthetic carbon fixation PhD supervisor (project leader): Henri Julien (LCQB, IBPS, Paris), [email protected] Co-Supervisor: Chéron Nicolas (Département de Chimie, ENS, Paris), [email protected] Download here

Biology/Computational Science Title: WNT/TCF-mediated transcriptional repression in embryonic development, the interaction with BARHL proteins (WNTOFF) PhD supervisor (project leader): Laine Elodie (LCQB, IBPS, Paris), [email protected] Co-Supervisor: Durand Béatrice (LBD, IBPS, Paris), [email protected] Download here

Biology/Physics/Mathematical Modeling Title: Molecular mechanism of a transient change in cell division control upon adaptation to sublethal levels of antibiotics PhD supervisor (project leader): Bianca Sclavi (LCQB, IBPS, Paris), [email protected] Co-Supervisor: Ciandrini Luca (CBS, Université de Montpellier), [email protected] Download here

You're viewing this site as a domestic an international student

You're a domestic student if you are:

a citizen of Australia or New Zealand,
an Australian permanent resident, or
a holder of an Australian permanent humanitarian visa.

You're an international student if you are:

intending to study on a student visa,
not a citizen of Australia or New Zealand,
not an Australian permanent resident, or
a temporary resident (visa status) of Australia.

Find a PhD or MPhil project with a scholarship

We offer a diverse range of postgraduate research projects that come with living stipend scholarships.

Scholarship-funded research projects

Explore our research projects with funded living stipend scholarships. You can filter by program type, research area and scholarship type, or use the keyword search field to find projects that suit your interests.

If you'd rather bring your own project, explore our scholarships (including top-up scholarships) and find a supervisor to support your project.

Detecting key concepts from low-quality data for better decision

Develop data analytics techniques – covering data understanding and enhancement, model development and fitting, and novelty detection – to aid decision-making in high-stake scenarios when data are less trustworthy.

Effect of physiological status on goat methane emissions

Investigate the relationship between a goats physiological status and its methane emissions to better understand their contribution to Australia's Carbon footprint.

Exoplanet direct imaging with the James Webb Space Telescope

Work on James Webb Space Telescope (JWST) exoplanet imaging, and the related kernel phase and coronagraphy modes of JWST by applying automatic differentiation and machine learning to enhance images.

How bacteria form antibiotic resistant biofilms

Dissect the structure, function and regulation of biofilms produced by antibiotic-resistant bacterial pathogens.

Metal-organic framework glass thin film membranes for gas separation

Help develop practical high-performance supported metal-organic framework (MOF) glass thin film membranes for gas separation by researching how to eliminate interfacial defects and grain boundaries.

New approaches to measuring single-molecule protein dynamics

Develop methods to incorporate novel-solvatochromic fluorophores into proteins and study the interaction of GPCR or G-protein conjugates using single-molecule dynamics and other techniques.

Preventing diabetes through taking small steps for big changes

Help to reduce diabetes through understanding the effectiveness, uptake, and implementation of a diabetes prevention program in community-based settings.

Tapping into non-English-language science in tackling global environmental challenges

Conduct multilingual synthesis of evidence on global environmental challenges, test the importance of non-English-language science, and explore methods of multilingual evidence synthesis.

Understanding how predictions modulate visual perception

This project will use cognitive neuroscience methods to explore how predictions impact how the brain processing incoming perceptual information.

Model interpretation and data-centric modeling for advanced traffic prediction (MINDMAP)

Develop theoretical frameworks and practical methods for enhancing the transferability, interpretability, and data-centric perspectives of machine learning-based traffic prediction models.

Driving Innovations in Biostatistics with Denise Scholtens, PhD

“I'm continually surprised by new data types. I think that we will see the emergence of a whole new kind of technology that we probably can't even envision five years from now…When I think about where the field has come over the past 20 years, it's just phenomenal.” — Denise Scholtens, PhD

Director, Northwestern University Data Analysis and Coordinating Center (NUDACC)
Chief of Biostatistics in the Department of Preventive Medicine
Professor of Preventive Medicine in the Division of Biostatistics and of Neurological Surgery
Member of Northwestern University Clinical and Translational Sciences Institute (NUCATS)
Member of the Robert H. Lurie Comprehensive Cancer Center

Episode Notes

Since arriving at Feinberg in 2004, Scholtens has played a central role in the dramatic expansion of biostatistics at the medical school. Now the Director of NUDACC, Scholtens brings her expertise and leadership to large-scale, multicenter studies that can lead to clinical and public health practice decision-making.

After discovering her love of statistics as a high school math teacher, Scholtens studied bioinformatics in a PhD program before arriving at Feinberg in 2004.
Feinberg’s commitment to biostatistics has grown substantially in recent decades. Scholtens was only one of five biostatisticians when she arrived. Now she is part of a division with almost 50 people.
She says being a good biostatistician requires curiosity about other people’s work, knowing what questions to ask and tenacity to understand subtitles of so much data.
At NUDACC, Scholtens and her colleagues specialize in large-scale, multicenter prospective studies and clinical trials that lead to clinical or public health practice decision-making. They operate at the executive level and oversee all aspects of the study design.
Currently, Scholtens is involved with the launch of a large study, along with The Ohio State University, that received a $14 million grant to look at the effectiveness of aspirin in the prevention of hypertensive disorders in pregnancy.
Scholtens first started her work in data coordinating through the Hyperglycemia Adverse Pregnancy Outcome (HAPO) study, which looked at 25,000 pregnant individuals. This led to a continued interest in fetal and maternal health.
When it comes to supportive working environments, Scholtens celebrates the culture at Feinberg, and especially her division in biostatistics, for being collaborative as well as genuinely supportive of each other’s projects. She attributes this to strong leadership which established a culture with these guiding principles.

Additional Reading

Read more about the ASPIRIN trial and other projects taking place at NUDACC
Discover a study linking mothers’ obesity-related genes to babies’ birth weight, which Scholtens worked in through the HAPO study
Browse all of Scholtens recent publications

Recorded on February 21, 2024.

Continuing Medical Education Credit

Physicians who listen to this podcast may claim continuing medical education credit after listening to an episode of this program..

Target Audience

Academic/Research, Multiple specialties

Learning Objectives

At the conclusion of this activity, participants will be able to:

Identify the research interests and initiatives of Feinberg faculty.
Discuss new updates in clinical and translational research.

Accreditation Statement

The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement

The Northwestern University Feinberg School of Medicine designates this Enduring Material for a maximum of 0.50 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

American Board of Surgery Continuous Certification Program

Successful completion of this CME activity enables the learner to earn credit toward the CME requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

All the relevant financial relationships for these individuals have been mitigated.

Disclosure Statement

Denise Scholtens, PhD, has nothing to disclose. Course director, Robert Rosa, MD, has nothing to disclose. Planning committee member, Erin Spain, has nothing to disclose. FSM’s CME Leadership, Review Committee, and Staff have no relevant financial relationships with ineligible companies to disclose.

Read the Full Transcript

[00:00:00] Erin Spain, MS: This is Breakthroughs, a podcast from Northwestern University Feinberg School of Medicine. I'm Erin Spain, host of the show. Northwestern University Feinberg School of Medicine is home to a team of premier faculty and staff biostatisticians, who are the driving force of data analytic innovation and excellence here. Today, we are talking with Dr. Denise Scholtens, a leader in biostatistics at Northwestern, about the growing importance of the field, and how she leverages her skills to collaborate on several projects in Maternal and Fetal Health. She is the Director of the Northwestern University Data Analysis and Coordinating Center, NUDACC, and Chief of Biostatistics in the Department of Preventive Medicine, as well as Professor of Preventive Medicine and Neurological Surgery. Welcome to the show.

[00:01:02] Denise Scholtens, PhD: Thank you so much.

[00:01:02] Erin Spain, MS: So you have said in the past that you were drawn to this field of biostatistics because you're interested in both math and medicine, but not interested in becoming a clinician. Tell me about your path into the field and to Northwestern.

[00:01:17] Denise Scholtens, PhD: You're right. I have always been interested in both math and medicine. I knew I did not want to be involved in clinical care. Originally, fresh out of college, I was a math major and I taught high school math for a couple of years. I really enjoyed that, loved the kids, loved the teaching parts of things. Interestingly enough, my department chair at the time assigned me to teach probability and statistics to high school seniors. I had never taken a statistics course before, so I was about a week ahead of them in our classes and found that I just really enjoyed the discipline. So as much as I loved teaching, I did decide to go ahead and invest in this particular new area that I had found and I really enjoyed. So I wanted to figure out how I could engage in the field of statistics. Decided to see, you know, exactly how studying statistics could be applied to medicine. At the time, Google was brand new. So I literally typed in the two words math and medicine to see what would come up. And the discipline of biostatistics is what Google generated. And so here I am, I applied to grad school and it's been a great fit for me.

[00:02:23] Erin Spain, MS: Oh, that's fantastic. So you went on to get a PhD, and then you came to Northwestern in 2004. And so tell me a little bit about the field then and how it's changed so dramatically since.

[00:02:36] Denise Scholtens, PhD: So yes, I started here at Northwestern in 2004, just a few months after I had defended my thesis. At the time there was really an emerging field of study called bioinformatics. So I wrote my thesis in the space of genomics data analysis with what at the time was a brand new technology, microarrays. This was the first way we could measure gene transcription at a high throughput level. So I did my thesis work in that space. I studied at an institution with a lot of strengths and very classical statistics. So things that we think of in biostatistics like clinical trial design, observational study analysis, things like that. So I had really classic biostatistics training and then complimented that with sort of these emerging methods with these high dimensional data types. So I came to Northwestern here and I sort of felt like I lived in two worlds. I had sort of classic biostat clinical trials, which were certainly, you know, happening here. And, that work was thriving here at Northwestern, but I had this kind of new skillset, and I just didn't quite know how to bring the two together. That was obviously a long time ago, 20 years ago. Now we think of personalized medicine and genomic indicators for treatment and, you know, there's a whole variety of omics data variations on the theme that are closely integrated with clinical and population level health research. So there's no longer any confusion for me about how those two things come together. You know, they're two disciplines that very nicely complement each other. But yeah, I think that does speak to how the field has changed, you know, these sort of classic biostatistics methods are really nicely blended with a lot of high dimensional data types. And it's been fun to be a part of that.

[00:04:17] Erin Spain, MS: There were only a handful of folks like you at Northwestern at the time. Tell me about now and the demand for folks with your skill set.

[00:04:26] Denise Scholtens, PhD: When I came to Northwestern, I was one of a very small handful of biostatistics faculty. There were five of us. We were not even called a division of biostatistics. We were just here as the Department of Preventive Medicine. And a lot of the work we did was really very tightly integrated with the epidemiologists here in our department and we still do a lot of that for sure. There was also some work going on with the Cancer Center here at Northwestern. But yeah, a pretty small group of us, who has sort of a selected set of collaborations. You know, I contrast that now to our current division of biostatistics where we are over 20s, pushing 25, depending on exactly how you want to count. Hoping to bring a couple of new faculty on board this calendar year. We have a staff of about 25 statistical analysts. And database managers and programmers. So you know, when I came there were five faculty members and I think two master's level staff. We are now pushing, you know, pushing 50 people in our division here so it's a really thriving group.

[00:05:26] Erin Spain, MS: in your opinion, what makes a good biostatistician? Do you have to have a little bit of a tough skin to be in this field?

Denise Scholtens, PhD: I do think it's a unique person who wants to be a biostatistician. There are a variety of traits that can lead to success in this space. First of all, I think it's helpful to be wildly curious about somebody else's work. To be an excellent collaborative biostatistician, you have to be able to learn the language of another discipline. So some other clinical specialty or public health application. Another trait that makes a biostatistician successful is to be able to ask the right questions about data that will be collected or already have been collected. So understanding the subtleties there, the study design components that lead to why we have the data that we have. You know, a lot of our data, you could think of it in a simple flat file, right? Like a Microsoft Excel file with rows and columns. That certainly happens a lot, but there are a lot of incredibly innovative data types out there: wearables technology, imaging data, all kinds of high dimensional data. So I think a tenacity to understand all of the subtleties of those data and to be able to ask the right questions. And then I think for a biostatistician at a medical school like ours, being able to blend those two things, so understanding what the data are and what you have to work with and what you're heading toward, but then also facilitating the translation of those analytic findings for the audience that really wants to understand them. So for the clinicians, for the patients, for participants and the population that the findings would apply to.

Erin Spain, MS: It must feel good, though, in those situations where you are able to help uncover something to improve a study or a trial.

[00:07:07] Denise Scholtens, PhD: It really does. This is a job that's easy to get out of bed for in the morning. There's a lot of really good things that happen here. It's exciting to know that the work we do could impact clinical practice, could impact public health practice. I think in any job, you know, you can sometimes get bogged down by the amount of work or the difficulty of the work or the back and forth with team members. There's just sort of all of the day to day grind, but to be able to take a step back and remember the actual people who are affected by our own little niche in this world. It's an incredibly helpful and motivating practice that I often keep to remember exactly why I'm doing what I'm doing and who I'm doing it for.

[00:07:50] Erin Spain, MS: Well, and another important part of your work is that you are a leader. You are leading the center, NUDACC, that you mentioned, Northwestern University Data Analysis and Coordinating Center. Now, this has been open for about five years. Tell me about the center and why it's so crucial to the future of the field.

[00:08:08] Denise Scholtens, PhD: We specialize at NUDACC in large scale, multicenter prospective studies. So these are the clinical trials or the observational studies that often, most conclusively, lead to clinical or public health practice decision making. We focus specifically on multicenter work. Because it requires a lot of central coordination and we've specifically built up our NUDACC capacity to handle these multi center investigations where we have a centralized database, we have centralized and streamlined data quality assurance pipelines. We can help with central team leadership and organization for large scale networks. So we have specifically focused on those areas. There's a whole lot of project management and regulatory expertise that we have to complement our data analytics strengths as well. I think my favorite part of participating in these studies is we get involved at the very beginning. We are involved in executive level planning of these studies. We oversee all components of study design. We are intimately involved in the development of the data capture systems. And in the QA of it. We do all of this work on the front end so that we get all of the fun at the end with the statistics and can analyze data that we know are scientifically sound, are well collected, and can lead to, you know, really helpful scientific conclusions.

[00:09:33] Erin Spain, MS: Tell me about that synergy between the clinicians and the other investigators that you're working with on these projects.

[00:09:41] Denise Scholtens, PhD: It is always exciting, often entertaining. Huge range of scientific opinion and expertise and points of view, all of which are very valid and very well informed. All of the discussion that could go into designing and launching a study, it's just phenomenally interesting and trying to navigate all of that and help bring teams to consensus in terms of what is scientifically most relevant, what's going to be most impactful, what is possible given the logistical strengths. Taking all of these well informed, valid, scientific points of view and being a part of the team that helps integrate them all toward a cohesive study design and a well executed study. That's a unique part of the challenge that we face here at NUDACC, but an incredibly rewarding one. It's also such an honor and a gift to be able to work with such a uniformly gifted set of individuals. Just the clinical researchers who devote themselves to these kinds of studies are incredibly generous, incredibly thoughtful and have such care for their patients and the individuals that they serve, that to be able to sit with them and think about the next steps for a great study is a really unique privilege.

[00:10:51] Erin Spain, MS: How unique is a center like this at a medical school?

[00:10:55] Denise Scholtens, PhD: It's fairly unique to have a center like this at a medical school. Most of the premier medical research institutions do have some level of data coordinating center capacity. We're certainly working toward trying to be one of the nation's best, absolutely, and build up our capacity for doing so. I'm actually currently a part of a group of data coordinating centers where it's sort of a grassroots effort right now to organize ourselves and come up with, you know, some unified statements around the gaps that we see in our work, the challenges that we face strategizing together to improve our own work and to potentially contribute to each other's work. I think maybe the early beginnings of a new professional organization for data coordinating centers. We have a meeting coming up of about, I think it's 12 to 15 different institutions, academic research institutions, specifically medical schools that have centers like ours to try to talk through our common pain points and also celebrate our common victories.

[00:11:51] Erin Spain, MS: I want to shift gears a little bit to talk about some of your research collaborations, many of which focus on maternal and fetal health and pregnancy. You're now involved with a study with folks at the Ohio State University that received a 14 million grant looking at the effectiveness of aspirin in the prevention of hypertensive disorders in pregnancy. Tell me about this work.

[00:12:14] Denise Scholtens, PhD: Yes, this is called the aspirin study. I suppose not a very creative name, but a very appropriate one. What we'll be doing in this study is looking at two different doses of aspirin for trying to prevent maternal hypertensive disorders of pregnancy in women who are considered at high risk for these disorders. This is a huge study. Our goal is to enroll 10,742 participants. This will take place at 11 different centers across the nation. And yes, we at NUDACC will serve as the data coordinating center here, and we are partnering with the Ohio State University who will house the clinical coordinating center. So this study is designed to look at two different doses to see which is more effective at preventing hypertensive disorders of pregnancy. So that would include gestational hypertension and preeclampsia. What's really unique about this study and the reason that it is so large is that it is specifically funded to look at what's called a heterogeneity of treatment effect. What that is is a difference in the effectiveness of aspirin in preventing maternal hypertensive disorders, according to different subgroups of women. We'll specifically have sufficient statistical power to test for differences in treatment effectiveness. And we have some high priority subgroups that we'll be looking at. One is a self-identified race. There's been a noted disparity in maternal hypertensive disorders, for individuals who self identify according to different races. And so we will be powered to see if aspirin has comparable effectiveness and hopefully even better effectiveness for the groups who really need it, to bring those rates closer to equity which is, you know, certainly something we would very strongly desire to see. We'll also be able to look at subgroups of women according to obesity, according to maternal age at pregnancy, according to the start time of aspirin when aspirin use is initiated during pregnancy. So that's why the trial is so huge. For a statistician, the statisticians out there who might be listening, this is powered on a statistical interaction term, which doesn't happen very often. So it's exciting that the trial is funded in that way.

[00:14:27] Erin Spain, MS: Tell me a little bit more about this and how your specific skills are going to be utilized in this study.

[00:14:32] Denise Scholtens, PhD: Well, there are three biostatistics faculty here at Northwestern involved in this. So we're definitely dividing and conquering. Right now, we're planning this study and starting to stand it up. So we're developing our statistical analysis plans. We're developing the database. We are developing our randomization modules. So this is the piece of the study where participants are randomized to which dose of aspirin they're going to receive. Because of all of the subgroups that we're planning to study, we need to make especially sure that the assignments of which dose of aspirin are balanced within and across all of those subgroups. So we're going to be using some adaptive randomization techniques to ensure that that balance is there. So there's some fun statistical and computer programming innovation that will be applied to accomplish those things. So right now, there are usually two phases of a study that are really busy for us. That's starting to study up and that's where we are. And so yes, it is very busy for us right now. And then at the end, you know, in five years or so, once recruitment is over, then we analyze all the data,

[00:15:36] Erin Spain, MS: Are there any guidelines out there right now about the use of aspirin in pregnancy. What do you hope that this could accomplish?

Prescribing aspirin use for the prevention of hypertension during pregnancy is not uncommon at all. That is actually fairly routinely done, but that it's not outcomes based in terms of which dosage is most effective. So 81 milligrams versus 162 milligrams. That's what we will be evaluating. And my understanding is that clinicians prescribe whatever they think is better, and I'm sure those opinions are very well informed but there is very little outcome based evidence for this in this particular population that we'll be studying. So that would be the goal here, would be to hopefully very conclusively say, depending on the rates of the hypertensive disorders that we see in our study, which of the two doses of aspirin is more effective. Importantly, we will also be tracking any side effects of taking aspirin. And so that's also very much often a part of the evaluation of You know, taking a, taking a drug, right, is how safe is it? So we'll be tracking that very closely as well. Another unique part of this study is that we will be looking at factors that help explain aspirin adherence. So we are going to recommend that participants take their dose of aspirin daily. We don't necessarily expect that's always going to happen, so we are going to measure how much of their prescribed dose they are actually taking and then look at, you know, factors that contribute to that. So be they, you know, social determinants of health or a variety of other things that we'll investigate to try to understand aspirin adherence, and then also model the way in which that adherence could have affected outcomes.

Erin Spain, MS: This is not the first study that you've worked on involving maternal and fetal health. Tell me about your interest in this particular area, this particular field, and some of the other work that you've done.

[00:17:31] Denise Scholtens, PhD: So I actually first got my start in data coordinating work through the HAPO study. HAPO stands for Hyperglycemia Adverse Pregnancy Outcome. That study was started here at Northwestern before I arrived. Actually recruitment to the study occurred between 2000 and 2006. Northwestern served as the central coordinating center for that study. It was an international study of 25,000 pregnant individuals who were recruited and then outcomes were evaluated both in moms and newborns. When I was about mid career here, all the babies that were born as a part of HAPO were early teenagers. And so we conducted a follow up study on the HAPO cohort. So that's really when I got involved. It was my first introduction to being a part of a coordinating center. As I got into it, though, I saw the beauty of digging into all of these details for a huge study like this and then saw these incredible resources that were accumulated through the conduct of such a large study. So the data from the study itself is, was of course, a huge resource. But then also we have all of these different samples that sit in a biorepository, right? So like usually blood sample collection is a big part of a study like this. So all these really fun ancillary studies could spin off of the HAPO study. So we did some genomics work. We did some metabolomics work. We've integrated the two and what's called integrated omics. So, you know, my work in this space really started in the HAPO study. And I have tremendously enjoyed integrating these high dimensional data types that have come from these really rich data resources that have all, you know, resulted because of this huge multicenter longitudinal study. So I kind of accidentally fell into the space of maternal and fetal health, to be honest. But I just became phenomenally interested in it and it's been a great place.

[00:19:24] Erin Spain, MS: Would you say that this is also a population that hasn't always been studied very much in biomedical science?

[00:19:32] Denise Scholtens, PhD: I think that that is true, for sure. There are some unique vulnerabilities, right, for a pregnant individual and for the fetus, right, and in that situation. You know, the vast majority of what we do is really only pertaining to the pregnant participant but, you know, there are certainly fetal outcomes, newborn outcomes. And so, I think conducting research in this particular population is a unique opportunity and there are components of it that need to be treated with special care given sort of this unique phase of human development and this unique phase of life.

[00:20:03] Erin Spain, MS: So, as data generation just really continues to explode, and technology is advancing so fast, faster than ever, where do you see this field evolving, the field of biostatistics, where do you see it going in the next five to ten years?

[00:20:19] Denise Scholtens, PhD: That's a great question. I think all I can really tell you is that I'm continually surprised by new data types. I think that we will see an emergence of a whole new kind of technology that we probably can't even envision five years from now. And I think that the fun part about being a biostatistician is seeing what's happening and then trying to wrap your mind around the possibilities and the actual nature of the data that are collected. You know, I think back to 2004 and this whole high throughput space just felt so big. You know, we could look at gene transcription across the genome using one technology. And we could only look at one dimension of it. Right now it just seems so basic. When I think about where the field has come over the past 20 years, it's just phenomenal. I think we're seeing a similar emergence of the scale and the type of data in the imaging space and in the wearable space, with EHR data, just. You know, all these different technologies for capturing, capturing things that we just never even conceived of before. I do hope that we continue to emphasize making meaningful and translatable conclusions from these data. So actionable conclusions that can impact the way that we care for others around us. I do hope that remains a guiding principle in all that we do.

[00:21:39] Erin Spain, MS: Why is Northwestern Medicine and Northwestern Feinberg School of Medicine such a supportive environment to pursue this type of work?

[00:21:47] Denise Scholtens, PhD: That's a wonderful question and one, honestly, that faculty candidates often ask me. When we bring faculty candidates in to visit here at Northwestern, they immediately pick up on the fact that we are a collaborative group of individuals who are for each other. Who want to see each other succeed, who are happy to share the things that we know and support each other's work, and support each other's research, and help strategize around the things that we want to accomplish. There is a strong culture here, at least in my department and in my division that I've really loved that continues to persist around really genuinely collaborating and genuinely sharing lessons learned and genuinely supporting each other as we move toward common goals. We've had some really strong, generous leadership who has helped us to get there and has helped create a culture where those are the guiding principles. In my leadership role is certainly something that I strive to maintain. Really hope that's true. I'm sure I don't do it perfectly but that's absolutely something I want to see accomplished here in the division and in NUDACC for sure.

[00:22:50] Erin Spain, MS: Well, thank you so much for coming on the show and telling us about your path here to Northwestern and all of the exciting work that we can look forward to in the coming years.

[00:22:59] Denise Scholtens, PhD: Thank you so much for having me. I've really enjoyed this.

[00:23:01] Erin Spain, MS: You can listen to shows from the Northwestern Medicine Podcast Network to hear more about the latest developments in medical research, health care, and medical education. Leaders from across specialties speak to topics ranging from basic science to global health to simulation education. Learn more at feinberg. northwestern.edu/podcasts.

Anonymous $1M Gift Bolsters American & New England Studies Program

Marina Dawn Wells (GRS’20,’24) examining a scrimshaw carving of a trans pirate, “Alwilda,” that a whaleman copied out of a book by Charles Ellms, The Pirates Own Book (1837). Photo by Drew Furtado/New Bedford Whaling Museum

Anonymous $1M Gift Bolsters American & New England Studies Program

It will create a public humanities fund to support phd students with research projects, internships.

PhD students in the American & New England Studies Program (AMNESP) can dream a little bigger next year thanks to an anonymous $1 million gift, part of which will create a new Public Humanities Fund to support research projects, award grants, and fund research-related activities beyond campus.

“I’m exploring the possibility of partnering with local institutions to fund internships that focus on public-facing work in the humanities,” says Joseph Rezek , a College of Arts & Sciences associate professor of English and AMNESP director.

“I’m also interested in receiving proposals from PhD students to fund projects of their own design—what’s your dream project?” Rezek says.

Income from the gift, expected to start flowing during the 2024-2025 school year, will also fund academic fellowships, outside speakers, conference travel, and the like. But Rezek and the faculty are most excited about the Public Humanities Fund and its potential to expand opportunities beyond the campus and help recruit top students.

Students in AMNESP can pursue traditional academic careers, but it’s no secret that lately there are more newly minted PhDs than there are jobs. These days many head for the public humanities, through internships and research projects at institutions like the Museum of Fine Arts, the Peabody Essex Museum, the Massachusetts Historical Society, the Boston Athenaeum, and others. Only about a third are on the New England track; among the others this year is a student whose project about the airspace in the American west is supported by a NASA fellowship.

AMNESP comprises a large PhD program, with around 30 active students at a time writing dissertations that cover all periods of American history and culture, from the colonial period to the present, along with a small undergraduate program and a related master’s program in preservation studies.

A small faculty steering committee helped Rezek shape the Public Humanities Fund plan.

I’m also interested in receiving proposals from PhD students to fund projects of their own design—what’s your dream project? Joseph Rezek

“I can tell you the spirit of the donation,” Rezek says, “which is that this donor supports traditional academic success and also the idea that we need highly educated, credentialed specialists to guide the general public through a story of American history that is accurate, rich, and engages the humanities, art, history, and politics, in all the complicated ways you would in a classroom. But [the donor] also supports the work that we’ve done historically in these other other kinds of institutions.”

For a sample of what public-facing work in the humanities can mean for a PhD student, swing down to the New Bedford Whaling Museum beginning Friday and check out Reflections , an exhibition in the museum’s San Francisco Gallery.

On display through October 27, the exhibition plumbs the museum’s vast photography collection for images of literal or metaphorical reflection. The Reflections text quotes Herman Melville in Moby-Dick : “Yes, as every one knows, meditation and water are wedded for ever.”

The exhibition was researched and curated by Marina Dawn Wells (GRS’20,’24), who uses they/them pronouns. Wells recently successfully defended their PhD in the AMNESP and is the photography collection curatorial fellow at the museum.

“I’m basically the steward of the photography collection, which is pretty incredible,” says Wells. “The collection numbers somewhere around 200,000 objects. It’s a vast collection that spans the history of photography, from when daguerreotypes were invented in 1839 up to the present.

“There are all different forms of photography within it, and I’ve been responsible for cataloging work and advocating for the photography collection at a departmental and interdepartmental level. I’ve curated a couple of really exciting projects and that feels like a big deal, actually.”

In addition to Reflections , Wells is deep into research for a major exhibition that won’t open until fall 2025, Strike a Pose, on portraiture and the more than 200 photography studios that thrived in New Bedford in the 19th century.

When Wells’ fellowship ends with the summer, they’ll be staying on at the Whaling Museum as assistant curator of history and culture.

“It’s a wonderful place to be, especially for an American studies–oriented scholar, because it is art, history, science, and culture,” they say. “The embeddedness of the interdisciplinary approach in this institution in particular is astounding.”

Wells’ dissertation, Making Men from Whales: Gender and American Whaling Art, 1814-1861 , looks mainly at scrimshaw as well as painting, prints, and other forms to decode the ways artworks about life at sea depicted and sometimes subverted traditional masculinity.

Between Wells’ freshly minted PhD and the new job at the museum, it makes a nice demonstration of how the BU program’s support of public humanities can be a game changer for students.

“It’s hugely valuable,” Wells says. “I’ve obviously benefited from the ways in which BU and the American & New England Studies Program have supported the importance of external experiences.

“A museum is just an ideal place for someone who’s a graduate of my program,” they say. “There’s a scarcity of academic jobs right now, and it’s so beneficial to think about what museums, what archives, what preservation societies, what national parks, what libraries that students can go into.”

Wells is just the kind of student Rezek is hoping will take advantage of the new fund.

“This is not someone who will benefit from the Public Humanities Fund, because they are graduating, but they are an example of exactly the kind of thing that we’re trying to do with it,” he says.

Explore Related Topics:

College of Arts & Sciences
Share this story
0 Comments Add

Staff Writer

Portrait of Joel Brown. An older white man with greying brown hair, beard, and mustache and wearing glasses, white collared shirt, and navy blue blazer, smiles and poses in front of a dark grey background.

Joel Brown is a staff writer at BU Today and Bostonia magazine. He’s written more than 700 stories for the Boston Globe and has also written for the Boston Herald and the Greenfield Recorder . Profile

Comments & Discussion

Boston University moderates comments to facilitate an informed, substantive, civil conversation. Abusive, profane, self-promotional, misleading, incoherent or off-topic comments will be rejected. Moderators are staffed during regular business hours (EST) and can only accept comments written in English. Statistics or facts must include a citation or a link to the citation.

Latest from BU Today

A video tour of stuvi i and stuvi ii, the weekender: april 25 to 28, sunday in the park with george opens at booth theatre, a rundown of the best thrift and vintage spots near bu, pov: the biden-trump rematch may mark the end of an era, combating loneliness and creating healthy relationships, five common sexual health myths debunked, global programs photo contest showcases bu’s worldwide adventures and experiences, book recommendations in honor of world book day, waste watchers, as we celebrate earth day, a reminder of what cannot be recycled at bu, bu honors best student employees and supervisor, women’s tennis heads to annapolis this weekend for 2024 patriot league tournament, reimagining cummington mall, pov: baseball needs to shake up the game—or risk a slow death, meet bu’s diy bicycle repair shop, women’s golf going for fourth patriot league title this weekend, the weekender: april 18 to 21, louis chude-sokei brings bu, spoken word, and dub reggae sounds to venice biennale.

More From Forbes

The schmidt science fellows for 2024 are announced.

Share to Facebook
Share to Twitter
Share to Linkedin

The 2024 cohort of Schmidt Science Fellows.

Eric and Wendy Schmidt have announced the 2024 cohort of Schmidt Science Fellows . As in years past, this year’s class of 32 fellows are all recent PhD’s who’ve been identified as some of the most outstanding early-career scientists in the world.

The Schmidt Science Fellows is supported by Schmidt Sciences , a philanthropic initiative co-founded in 2024 by former Google CEO and Chairman Eric Schmidt and his wife Wendy, President of the Schmidt Family Foundation.

The current class is the seventh cohort in the program, which is delivered in a partnership with the Rhodes Trust. Since its inception, the Schmidt Science Fellows has supported 177 Fellows, nominated by 62 institutes across the globe.

Considered one of the most prestigious scientific postdoctoral awards in the world, Schmidt Science Fellows are awarded support for either one or two years in a field of study that represents a pivot from their Ph.D concentration.

An emphasis is placed on encouraging interdisciplinary research with the potential to address some of the world’s most pressing challenges.

“Breaking down silos and harnessing the power of interdisciplinary science holds the key to tackling humanity's most pressing challenges, from global health and protecting our environment to ensuring we can develop new technologies that are both safe and foster societal good,” said Eric Schmidt, in a news release. “The 2024 Schmidt Science Fellows are exceptionally talented in their fields and with the Program’s support we hope to enhance the impact of their work.”

Rudy Giuliani And Mark Meadows Indicted In Arizona Fake Electors Case

Tupac shakur s estate challenges drake over ai vocals in kendrick lamar diss song, apple iphone 16 unique all new design promised in new report.

In addition to an annual stipend of $110,000, the fellows receive individualized mentoring and participate in a year-long Science Leadership Program that helps them cultivate the skills, experience and networks to be expected from interdisciplinary science leaders.

Each year, the Schmidt Science Fellows program works with nearly 100 of the world’s leading science and engineering institutions to identify the most promising candidates for the fellowships. Nominated candidates are selected through a process that includes an academic review by leaders in their home disciplines and final interviews with panels of experts, including senior representatives from many scientific disciplines and different business sectors.

The 2024 cohort represents 17 nationalities nominated by 26 of the world’s leading institutions across North America, Europe and Asia. Four institutions had Fellows selected for the first time this year: Agency for Science, Technology and Research (A*STAR), Singapore; Nanyang Technological University, Singapore; Max Planck, Germany; and the University of Hong Kong, Hong Kong. Eighteen of the fellows were nominated by universities in the United States.

The full list of the 2024 Schmidt Science Fellows can be found here . Their areas of study span a wide range of topics in biology, neurosciences, engineering, cancer diagnosis and treatment, artificial intelligence, earth sciences and climate change. As examples:

Ajinkya Dahake, nominated by Cornell University, will explore how mosquitoes distinguish between humans and other animals or plants, leading to the possible discovery of new strategies to control the spread of mosquito-borne diseases.
Bruna Martins Garcia, nominated by the Max Planck Institute, will be investigating metastasis — the ability of cancer cells to move to other organs — focusing on understanding organ-specific metastasis.
Jacob Beckham, nominated by Rice University, will be studying the role that the gut microbiome, a digestive tract bacteria, plays in anxiety disorders.
Elio Challita, nominated by the Georgia Institute of Technology, will be developing a microrobot that will mimic the ability of insects to monitor and analyze environmental conditions such as water contamination.
Olivia Goldman, nominated by The Rockefeller University, will use a mouse model of headache to explore how viruses can induce headaches like those seen in people suffering from long-COVID.
Erin Huiting, nominated by the University of California at San Francisco, will combine bioinformatics and genome engineering to learn how innate immune receptors help make plants resistant to certain pathogens. The research could have implications for more sustainable agriculture production and improved climate change mitigation.

About Schmidt Sciences

Schmidt Sciences is a philanthropic efforts that “aims to accelerate and deepen our understanding of the natural world and develop solutions to real-world challenges for public benefit.”

According to its website, an emphasis is placed on “identifying under-supported or unconventional areas of exploration and discovery with the potential for high impact.” It focuses on AI & Advanced Computing, Astrophysics and Space, Biosciences, Climate, and Cross-Science.

"It's at the edges of things—ecosystems, borders, disciplines—where the most interesting ideas are developed, solutions that don't arise from any single approach," said Wendy Schmidt. "We're excited to welcome the 2024 cohort of Schmidt Science Fellows to approach these edges, look at problems anew, share insights with each other and the world and, we hope, go on to develop solutions to some of humanity's most pressing challenges."

Editorial Standards
Reprints & Permissions

ECEE students earn college undergraduate awards 2024

Two exceptional students from the Department of Electrical, Computer and Energy Engineering (ECEE) have earned 2024 Graduating Student Awards from the College of Engineering and Applied Science.

These honors are awarded to seniors who are nominated by faculty, staff or fellow students for their outstanding contributions and achievements.

ECEE students will celebrate graduation on Thursday, May 9, 2024 from 4-6 p.m. at the Business Field.

Perseverance Award

Bruno Armas BS in Electrical & Computer Engineering

This award recognizes undergraduate students who persevere despite adversity – above and beyond the inherent perseverance needed in any engineering major.

What are your plans after graduation? I am still seeking full-time employment. I have two trips to California in the works with one road trip with friends and the other to go to San Diego Comic Con.

Your perseverance speaks volumes. How did perseverance and resilience help you tackle challenges? Since the beginning, my college career has been characterized by numerous obstacles, setbacks and challenges, which all seemed insurmountable at the time. No challenge has changed and defined me more than taking nearly two years away from school to support my family during the COVID-19 pandemic. No matter how impossible my situation seemed, commuting more than 40 miles for two semesters while taking a full course load, I always reminded myself that I am living out my dream. This was the second chance that I fought for and that I never take my education for granted.

How has your involvement with CU Engineering helped your journey? I continued to work at the BOLD Center as a peer mentor to scholars and met with my academic coach every two weeks. I was involved as a board member of the Society of Hispanic Professional Engineers. As a student leader, I shared my lessons learned and provided support to other engineering students. I’ve been eager to share those experiences through my leadership in the BOLD community and as a leader. I will be graduating this upcoming May with a degree in electrical and computer engineering. The sacrifices and changes I made ultimately led to success and a foundational achievement that has brought me to this moment today.

What will you miss the most from your CU Engineering experience? What I will miss the most from CU Engineering were the long nights in the electronics lab with my friends.

What has been an important moment during your time with Electrical, Computer and Energy Engineering? My favorite memory at ECEE is the eruption of excitement that my lab partner, Sam Feller, and I felt when we were finally able to pulse an LED for three seconds after hours of working in embedded systems.

What is a piece of advance you have for future engineering students? My advice for future students is that your goals can always be reality. Be flexible to accomplish your goals in ways that you didn’t envision. No matter the outcome, keep working for your dreams. Always be solution-focused despite obstacles, setbacks and hardships. I have accomplished this not only for me, but for everyone who helped me on this journey.

Community Impact Award

Jasleen K. Batra BS in Electrical & Computer Engineering

This award recognizes undergraduate students who contribute to improving their department, program, college, university and/or local community.

What are your plans after graduation? I am pursuing a master’s in electrical engineering at CU Boulder to conduct thesis research in radiative transfer and remote sensing!

What has been an important moment during your time with Electrical, Computer and Energy Engineering? Midway through my first semester of sophomore year, I switched into the Electrical & Computer Engineering major, which led me to being incredibly behind in classes. I remember struggling a lot each week, and I frequently questioned if I had made the right decision switching majors. One week in particular, I was overwhelmed with staying up to date with new coursework. I reached out to a friend who gave me advice I still carry with me two years later.

He told me the responsibility in obtaining my degree was mine and mine only. If I was serious about the degree, I’d do anything and everything it took to finish it. It reminds me of one of my favorite poems, Invictus, where the author finishes the poem with, “It matters now how strait the gate, How charged with punishments the scroll, I am the master of my fate, I am the captain of my soul.” This moment highlighted just how empowering it can be to take hold of a circumstance, even if less than ideal. Here I was, questioning if I had what it took to be an engineer, absolutely entrenched within a difficult academic situation. This is my favorite memory at ECEE because it showed me that good engineers and scientists struggle, but being able to put yourself in the driver’s seat makes life easier to manage.

What will you miss the most from CU Engineering? I am going to miss the plethora of research opportunities. Through my time in undergrad, I have been involved with a variety of remote sensing, quantum, and space weather research projects through the College of Engineering and Applied Science, and it’s amazing to me that these opportunities are open to students. From a young age, I was always curious about weather and how it worked. When I got to university, I was able to explore weather-based research that provided me a more solid understanding of weather dynamics not only here on Earth, but in space as well. When you do research, it feels like you’re contributing to something bigger than yourself, and it’s an amazing feeling.

What is a piece of advice you have for future engineering students? The best way to succeed in engineering is by supporting, collaborating and receiving support. Your strongest relationships will come from struggling alongside others, whether that be through homework, exams or through life in general. I am still in this major because I had a support system. Be the reason someone stays in engineering. There will always be a million reasons to not do something. By holding out a helping hand, you will be surprised by who you meet, who will inspire you and who will introduce you to the next step in your career. And while you’re developing your career, you’ll know who to point your friends and peers to as they develop theirs.

PhD students earn major NSF graduate research fellowships

Innovation unveiled: ECEE students to showcase design projects

Zoya Popovic elected to the National Academy of Inventors

Apply Visit Give

Departments

Ann and H.J. Smead Aerospace Engineering Sciences
Chemical & Biological Engineering
Civil, Environmental & Architectural Engineering
Computer Science
Electrical, Computer & Energy Engineering
Paul M. Rady Mechanical Engineering
Applied Mathematics
Biomedical Engineering
Creative Technology & Design
Engineering Education
Engineering Management
Engineering Physics
Environmental Engineering
Integrated Design Engineering
Materials Science & Engineering

2024 Catalyst Fund to Support Innovative Projects in Equity, Diversity, and Inclusion

The Duke University School of Medicine Office of Equity, Diversity and Inclusion has announced the recipients of the Equity, Diversity, and Inclusion Catalyst Fund . The fund provides resources for innovative projects, interventions, and programs in equity, diversity, and inclusion that have the potential to scale or translate into broader School of Medicine initiatives. A total of seven projects were selected, each of which will receive funding for a 12-month period.

The projects selected as winners of the 2024 EDI Catalyst Fund are:

“Administrative Support Staff Professional Development Pilot Program,” project directors: Pamela Keels; Julius Wilder, MD, PhD; and Camille Fulbright. Collaborators: Rodney Reeves; Lowell Tyler; and Erica Taylor, MD.
“Association of Women Surgeons Mentorship Pods,” project director: Gayle DiLalla, MD. Collaborators: Hana Shafique, MS2; Alexandria Soto, MS3; Dana Rowe, MS3; Shannon Barter, PGY-3.
“Developing and Implementing an Equity, Diversity, and Inclusion (EDI) Education in Obstetrics and Gynecology: EVOLVE EDI Education,” project directors: Latoya Patterson, MD, MPH; and Sarahn Wheeler, MD, MHS. Collaborators: SirTauria Hilliard; and Monica Vallier.
“Developing a Pediatric Justice League: Using Restorative Justice Practices to Improve Workplace Culture in the Department of Pediatrics,” project director: Sydney Allgood. Collaborators: Kathleen Bartlett, MD; Catherine Hart, M.Ed.; and Jasmine Willis-Wallace, Ed.D., MS.
“Honoring Diversity and Catalyzing Belonging through Inclusive Communications,” project directors: Susan Gallagher; and Lindsay Gordon-Faranda. Collaborators: Jamie Botta; Jessica Bronchick; Rosie Canizares; Bernadette Gillis; Lynn Labuda; Beverly Murphy; Abby Parcell; Cara August; Stephanie Lopez; Valerie Marino; Minerva Matos-Garner; Andy Medlin; Sarah Morrison; and Natalie Sayewich.
“Increasing Diversity, Equity, and Inclusive Excellence in Faculty Searches: A Toolkit for Educators and Leaders,” project directors: Rachel Porter, PhD, MEd; and Quincy Jones, MSW, MHS, PA-C. Collaborators: Gary Johnson, PT, DPT, ATC/L; Jean Mesaros, PharmD; Linwood Webb; and Jacquetta Melvin, MPH, PA-C.
“Advancing Unit-level Climate & EDI through Collaboration within the Duke University School of Medicine,” project directors: Michael Fern, PhD; and Monica Elam. Collaborators: Amy Porter-Tacoronte; Beth Glasscock; Lowell Tyler; Michelle Smith; Robin Famiglietti; and Willette Wilkins.

The projects were chosen based on their potential for positive impact in one or several areas, including strategies that enhance the climate of inclusion and belonging and strategies that infuse equity and inclusion in recruitment, retention, and promotion of faculty and staff.

“These initiatives represent ambitious and innovative strategies with strong potential for advancing our shared goals in equity, diversity, and inclusion,” said Kevin Thomas, MD, vice dean for equity, diversity, and inclusion. “Collaboration across units enhances the potential for these initiatives to expand and evolve.”

The Office of Equity, Diversity and Inclusion launched the EDI Catalyst Fund earlier this year. Staff and faculty in School of Medicine were invited to submit requests for proposal for the award.

The funding period for the Catalyst Fund is from April 2024 to April 2025.

Related News

Accepted Students Day Hosted for Upcoming Pathway Scholars Students

Family Medicine Residency Payson Welcomes First Cohort

Scholarly Project Profile: Ankedo Warda

Ben Conner and his wife at the Class of 2024 Match Day

Commencement Profile: Benjamin Conner

Thomas Kelly

On Monday, May 6, the University of Arizona College of Medicine – Phoenix will hold its 14 th Commencement . Led by a pipe and drum corps, the Class of 2024 will process through downtown Phoenix, finishing at the Orpheum Theatre for their official ceremony. The day marks the beginning of the next phase in their journey as physicians. The college profiled a series of graduating students to commemorate the milestone.

Meet Benjamin Conner

Benjamin (Ben) Conner grew up in Central Pennsylvania and attended Penn State University for his undergraduate degree. He worked in a paleoanthropology lab that was studying bone morphology, investigating how and why humans move the way they do.

The experience ignited Ben’s interest in human movement and propelled him to earn a master’s in Biomechanics and Movement Science at the University of Delaware, where he studied musculoskeletal development and motor control in children with cerebral palsy.

Working with this patient population and engaging in more clinically focused research affirmed Conner’s desire to contribute to research that could improve quality of life. Teaming up with clinical collaborators for his research also allowed him to observe how important it was to look through a clinical lens and ask patient-centered questions.

This, ultimately, motivated Conner to pursue MD/PhD training at the University of Arizona College of Medicine – Phoenix, where he completed his dissertation on robotic gait training for children with cerebral palsy and finished four years of medical school. He credits the college with providing him excellent clinical training.

Conner’s journey to date has been catalyzed by truly excellent support, mentorship and friendships. First and foremost, he wanted to thank his parents, who set him up for success early on in life, and his wife, who encouraged him through several long years of MD/PhD training.

Lastly, Conner wanted to thank his PhD co-advisors, Zachary Lerner, PhD and Michael Kruer, MD, who entrusted him to lead clinically focused research and championed his goal of becoming a physician-scientist in PM&R.

Conner’s pursuit of an MD/PhD has been extremely rewarding and all the friends he has made throughout the process have helped to make it even more gratifying.

On Match Day, what was it like discovering where you were headed for residency?

The buildup to Match Day was a combination of excitement and nerves. I felt good about my rank list, and while I would have been happy to match at any of the programs I had ranked, my #1 choice was my #1 for a reason!

To prepare, I had gone over the scenario of matching at several different programs in my head, considering the pros and cons of each, while also trying to trust that I would match at the program that was best for me. So, when I saw that I had matched at my first choice, I was truly elated. It felt like my efforts to date and vision for my future had all aligned, and I could not be any more excited to start my residency training now!

What’s Next?

What excites you most about your upcoming residency? Where are you headed?

I’ll be sticking around Phoenix for another year, as I complete my Preliminary Medicine Internship at Banner – University Medical Center Phoenix, and then moving to Boston, MA, for my Physical Medicine & Rehabilitation (PM&R) residency at Spaulding/Harvard.

I am most excited about taking the next step toward my ultimate career. I have been a lifelong student, literally, and I now feel ready to take on the responsibilities and opportunities of being a resident.

What inspired you to pursue this specialty?

I personally value an active lifestyle and see movement as medicine. I wanted to pursue a specialty that aligned with this perspective and gave me the opportunity to help my patients be as active and independent as possible.

I am grateful to have had great mentorship that led me toward this specialty. My late mentor, Bob Gorinski, jumpstarted my interest in rehabilitation medicine and demonstrated first-hand the rewarding profession of restoring a person’s ability to be active and independent.

Tim Ryan, PhD, at Penn State gave me the opportunity to engage in exciting research and taught me important principles of being a scientist. Christopher Modlesky, PhD, and Jeremy Crenshaw, PhD, co-mentors of my master’s program and leading experts in rehab and musculoskeletal research, gave me the tools to be a successful investigator and inspired and supported my aspirations for an MD/PhD in the field of rehabilitation.

For his Scholarly Project, Conner investigated robotic walking therapy for children with cerebral palsy

The College of Medicine – Phoenix Culture

Looking back, what’s your favorite medical school memory?

Having spent the past seven years at the College of Medicine – Phoenix for my MD/PhD program, it is difficult for me to pick out a single favorite memory from my time here. Overall, though, my favorite memories involve the life I have been able to build alongside medicine. I moved to Phoenix without knowing a soul within a 300-mile radius, but quickly made some lifelong friends.

We enjoyed countless adventures together, bike-packing across states and hiking the Grand Canyon. We lived through a pandemic and our circle of friends became even closer (metaphorically, of course – six-feet away!). I connected to the community through volunteer work at an adaptive outdoor rec group and even spent 12 days on an adaptive rafting trip down the Colorado River during my MS3 year. I married my wife, and our close friends bought houses and started their own families. Life kept moving as my training went on, and I feel so fortunate to have been able to enjoy mine as much as I did during this time.

Earning a Dual Degree

How do you think earning an MD/PhD will benefit you most in your career as a physician? And what were some of the challenges of taking on that dual degree?

An MD/PhD combined degree program teaches you the skills necessary to bridge the gap between laboratory findings and clinical practice, and my hope is to apply these skills to my own career as a physician-scientist. Specifically, within the PM&R field, I plan to continue to help develop and test novel rehabilitation interventions and assistive devices for the patient populations that I encounter in the clinic — with a strong focus on patient-centered approaches that are practical and accessible for most individuals.

There are several challenges to MD/PhD training, and only those interested in a physician-scientist career should really consider pursuing this combined degree. My original class formed close bonds during the pre-clerkship years, so it was difficult to part ways with them as I transitioned into my PhD years. It was then bittersweet to watch them match and graduate while I was still working toward my dissertation, especially as some of them moved out of state for residency. At the same time, I was excited to have some of my original classmates as the residents I worked with once I returned for clinical rotations, and to see how far they had come in their own training.

A PhD also takes considerable work, and it was difficult to make time to stay fresh with clinical skills and medical knowledge. So, transitioning back to clerkships after years off from the clinical world was challenging. I felt like the headspace I was in for my PhD program was different from the one I would need to succeed on clinical rotations, and I was concerned that I had lost a lot of what I had learned during the pre-clerkship years. Fortunately, my pre-clerkship knowledge came back fairly quickly, and I found that while my clinical skills were rusty, the thought processes I had honed during my PhD years were incredibly useful on rotations.

So, while there were certainly challenges during MD/PhD training, there were also several upsides, and I am thankful to have experienced a journey of growth and learning.

About the College

Founded in 2007, the University of Arizona College of Medicine – Phoenix inspires and trains exemplary physicians, scientists and leaders to optimize health and health care in Arizona and beyond. By cultivating collaborative research locally and globally, the college accelerates discovery in a number of critical areas — including cancer, stroke, traumatic brain injury and cardiovascular disease. Championed as a student-centric campus, the college has graduated more than 800 physicians, all of whom received exceptional training from nine clinical partners and more than 2,700 diverse faculty members. As the anchor to the Phoenix Bioscience Core , which is projected to have an economic impact of $3.1 billion by 2025, the college prides itself on engaging with the community, fostering education, inclusion, access and advocacy.

IMAGES

IBAB-Biocon Research Project 2024-JRF Position Leading to PhD
PhD Projects Research Guide (Worldwide No1 PhD Guidance)
Singapore International Graduate Award 2024 for PhD Students, Singapore
Phd Computer Science Research Proposal : Procedures for Student
Stages of current PhD project.
Free 2024 Project Timeline Template

VIDEO

2024 GOALS
DU PHD ADMISSION 2023-24| DELHI UNIVERSITY PHASE III ADMISSION| DELHI UNIVERSITY NEW PHDNOTIFICATION
Multiple Teaching Post Openings JNU 2024
Admissions 2024: Third Provisional Merit List of Bachelor's Degree Program for Academic Year 2024
IIT Guwahati PhD Seats Update 2024||Apply Now #phdadmissions #iitguwahati #latestphdform
Multiple Ph.D./Projects/JRF Openings 2024 #biologicalsciences #csirnetjrf #ccmb #jrf #biotechnology

COMMENTS

The 2024 PhD Project Annual Conference
The 2024 PhD Project Annual Conference . March 21-22, 2024. Hyatt Regency O'Hare. Floorplan ...
PDF 2024 PhD Project Conference
2024 PhD Project Conference Date Time (CT) Session Thursday, March 21 11:00 am Registration Opens 12:00 pm - 1:00 pm Lunch 1:00 - 2:00 pm Welcome Keynote Address: Dean Ian Williamson . University of California, Irvine . 2:00 - 3:00 pm. The Ph.D. Lifecycle: Setting the Stage .
Life Changing Moments
March 21-22, 2024. The flagship event for The PhD Project is our annual conference for potential doctoral students. At this 2-day conference, you can network with doctoral students, business school representatives, professors and sponsor organizations, all in one place. With demonstrated success in creating more diverse business faculty, we are ...
PhD Programmes, Research Projects & Studentships in the UK & Europe
We have fully funded studentships for you! Three 3-year PhD Funded Studentships in the School of Medicine. Department of Health Technology and Informatics. PhD Studentship opportunities in the College of Business and Social Sciences. Non-Clinical PhD studentships for informatics and data science researchers.
PhD Projects 2024
PhD opportunities for science graduates. We are now advertising five fully-funded PhD projects. The deadline for application is Wednesday 06 March 2024. Below you will find a link to further information about our application process, our application portal and mailing list, should you wish to be notified about future PhD opportunities.
Annual Conference
The PhD Project's Annual Conference is our flagship event. During the conference, we give prospective doctoral students a realistic look at every phase of the PhD journey as well as an opportunity to network with current doctoral students, business school representatives, professors and partner organizations — all in one place.
Who We Are
For more than 27 years, The PhD Project has helped change the future workforce by providing historically underrepresented students a model of achievement and businesses a powerful way to enrich the talent pipeline. We support the creation of business PhDs from historically underrepresented groups - transforming business education and business
PhD Projects 2024: Astrophysics
PhD projects in astrophysics for our STFC studentships 2024 are listed below. Probabilistic deep learning for cosmology and beyond (Prof. Jason McEwen) Understanding exoplanets and their host stars using large data sets and AI (Dr. Vincent Van Eylen) Studying the Universe with neutrinos (Prof. Kinwah Wu)
PhD Projects 2024
PhD Research Projects on offer at the IfA At the Institute for Astronomy, we study every astronomical scale from the solar system up to the large-scale structure of the Universe. Listed below you will find the wide range of PhD projects that are offered for entry in September 2024.
PhD Projects
PhD Projects. Projects on offer for 2024 entry will be progressively added here in December and January. The projects themselves may evolve somewhat before October 2024. We strongly encourage you to come to the open day on November 29th, 2023, to discuss the projects with potential supervisors. Information about the open day can be found here ...
PDF 2024 PhD projects and supervisory teams Doctoral Fellowships for Clinicians
A PhD project for the 2024 doctoral clinical fellows programme with Mike Devine (primary supervisor, Crick) and Selina Wray (UCL) Neurodegenerative conditions such as Parkinson's, Alzheimer's and motor neuron disease are common, extremely debilitating, and currently incurable. They all feature the progressive loss of neurons within the
Bartlett PhD Research Projects 2024
PhD Research Projects 2024 is the eighteenth annual conference and exhibition of doctoral research at The Bartlett School of Architecture, UCL. This publication presents work by students undertakin...
PhD projects 2024
PhD projects 2024. October 24, 2023. Many of our PIs are recruiting doctoral candidates in this year's application round. Below you can find their project proposals or research descriptions. Get inspired by these to draft the research proposal for your application. Your research proposal should be longer than the summary provided here ...
2024 PhD Program
The i-Bio international PhD Program 2024 is opening 2 PhD positions in co-supervision to work at the interface between biology and other scientific disciplines. The doctoral contracts benefit from an environment of 10 k€ to be used for the benefit of the doctoral student. ... PhD project PhD students will receive a salary for 3 years from ...
PhD Projects
Two PhD projects are available as part of Professor Yap's ARC Laureate Program which commences in 2024. This prestigious 5-year program aims to understand how cells communicate with one another by mechanical force to detect injury in epithelial tissues such as the gastrointestinal tract and embryonic skin.
PhD Management of Projects (2024 entry)
Our postgraduate research programmes in Management of Projects offer the opportunity to study in a multi-disciplinary team alongside leading academics in the field. ... For entry in the academic year beginning September 2024, the tuition fees are as follows: PhD (full-time) UK students (per annum): Band A £4,786; Band B £7,000; Band C £ ...
PhD projects available in the 2024 call
Please find below the list of PhD projects and the teams welcoming a PhD student in the 2024 call. Note that this list can be updated until April 15th. Deciphering the role of the adhesive switch between Cadherin and Integrin during epithelial cell cytokinesis. Formation and maintenance of intestinal microvilli in C. elegans.
2024 PhD Projects
2024 PhD Projects. Any of the projects listed below can be selected if you wish to apply for a NIHR Maudsley BRC 3-year PhD studentship to commence October 2024. These projects are categorised by the primary NIHR Maudsley BRC strategic goal applicable to each research study. As many projects align with more than one strategic goal and more than ...
Industrial PhD Scheme
Doctoral education in ICT security and cryptology for persons with security clearance. In 2020, the Industrial PhD and Public Sector PhD schemes announced funds for 18 doctoral degree projects in ICT security and cryptology. Thus far, funding has been allocated to 16 out of 18 projects, meaning that funding is still available for two projects.
PhD Projects 2024: Solar Physics
PhD projects in Solar Physics for our STFC studentships 2024 are listed below. Unveiling the Sun, next generation studies of the Sun's magnetic activity (Prof. Lucie Green); Fast Magnetic Reconnection in Solar Flares - Preparing for Solar-C (Prof. Sarah Matthews); The Link Between Solar Coronal Heating and Particle Acceleration (Dr. Hamish Reid)
Available projects for research degrees
3-D food printing. Closing on 1 February 2024 Prof Roger Stanley Scholarship available. 3-D printing valorisation of food wastes. Closing on 1 June 2024 Prof Roger Stanley Scholarship guaranteed. Beating smoke taint with sparkling wine. Closing on 1 June 2024 Dr Samantha Sawyer Scholarship available. Biological control in apple orchards.
PhD Projects 2024
PhD supervisor (project leader): Cauli Bruno (NPS, IBPS, Paris), [email protected] Co-Supervisor: Soula Hédi (Nutriomics, Paris), [email protected] Download here. Biology/Chemistry Title: CALVINUPGRADE - redesign enzymes to improve photosynthetic carbon fixation PhD supervisor (project leader):
Find an available PhD, MPhil project
Find a PhD or MPhil project with a scholarship We offer a diverse range of postgraduate research projects that come with living stipend scholarships. Scholarship-funded research projects. Explore our research projects with funded living stipend scholarships. You can filter by program type, research area and scholarship type, or use the keyword ...
Driving Innovations in Biostatistics with Denise Scholtens, PhD
Northwestern University Feinberg School of Medicine is home to a team of premier faculty and staff biostatisticians who are a driving force of data analytic innovation and excellence. In this episode, Denise Scholtens, PhD, a leader in biostatistics at Feinberg, discusses the growing importance of the field of biostatistics and how she leverages her skills to collaborate on several projects in ...
Anonymous $1M Gift Bolsters American & New England Studies Program
April 22, 2024. Joel Brown. PhD students in the American & New England Studies Program (AMNESP) can dream a little bigger next year thanks to an anonymous $1 million gift, part of which will create a new Public Humanities Fund to support research projects, award grants, and fund research-related activities beyond campus.
The Schmidt Science Fellows For 2024 Are Announced
The 2024 cohort of Schmidt Science Fellows. Eric and Wendy Schmidt have announced the 2024 cohort of Schmidt Science Fellows. As in years past, this year's class of 32 fellows are all recent PhD ...
ECEE students earn college undergraduate awards 2024
Two exceptional students from the Department of Electrical, Computer and Energy Engineering (ECEE) have earned 2024 Graduating Student Awards from the College of Engineering and Applied Science.. These honors are awarded to seniors who are nominated by faculty, staff or fellow students for their outstanding contributions and achievements.
2024 PhD Recognition Ceremony
Friday, May 24 at 5:30 p.m. At this event, we will celebrate and recognize the significant achievements of doctoral PhD, JSD, and DMA graduates from August '23, December '23, and expected May '24 and August '24. This special ceremony is for all Doctoral candidates to be individually recognized on stage and welcomed into the academy of ...
2024 Catalyst Fund to Support Innovative Projects in Equity, Diversity
A total of seven projects were selected, each of which will receive funding for a 12-month period. The projects selected as winners of the 2024 EDI Catalyst Fund are: "Administrative Support Staff Professional Development Pilot Program," project directors: Pamela Keels; Julius Wilder, MD, PhD; and Camille Fulbright.
Commencement Profile: Benjamin Conner
An inaugural graduate of the college's MD/PhD program, Conner hopes to help patients lead physically active lifestyles. On Monday, May 6, the University of Arizona College of Medicine - Phoenix will hold its 14th Commencement. Led by a pipe and drum corps, the Class of 2024 will process through downtown Phoenix, finishing at the Orpheum ...