Open Research Central

Discretionary Award - Open research

Open Research Central The open access movement has demonstrated that "openness" is a benefit to the creation, dissemination, and reuse of knowledge. Through a variety of policies and initiatives, there is renewed momentum for sharing research outputs as part of a more connected and collaborative open research ecosystem.  However, there remains a need for consensus around how best to deliver a research dissemination system that maximises the benefits for both science and society, and the researchers upon which such a system depends.

Open Research Central (ORC) is a not-for-profit organization that aims to change the paradigm for primary research dissemination by bringing together key representatives across the scholarly ecosystem to define standards, build a movement to expand adoption of these standards, encourage the community to provide researchers with services that meet these standards and promote these standards.

To build further momentum and adoption globally of open research publishing approaches, the ORC Board wish to secure resource for 18 months to underpin more significant fund raising efforts to enable ORC to deliver on its mission, to develop and start to put into place a sustainability plan, and to support the Board in the day-to-day running and management of ORC.


Discretionary Award - Policy

Advancing the global health agenda with the Paris Peace Forum The Paris Peace Forum will host a series of discussions to maintain the partnership developed by ACT-A  (Access to COVID-19 Tools Accelerator) and the governance of global health at the top of the political agenda and further deliver concrete solutions while contributing to the construction of an overall governance framework in the sector. The proposal includes hosting discussions taking place in the framework of a pilot, year-long partnership between the Forum and Wellcome Trust. These discussions would mobilize stakeholders of the Forum’s community and beyond. The Forum would naturally seek Wellcome’s guidance and advice on the scope, topics, invitees, and outputs of these discussions. Stakeholders would be invited to participate in each discussion based on their institutional focus and expertise and on the basis of their capacity to contribute to and implement the desired outcomes. With the support provided by the Wellcome Trust, the Forum could convene two roundtables in 2021, to provide for sufficient time for preparation, eventually for follow-up actions in between and potentially to leverage to key moments in the annual Forum cycle: the Spring meetings of the Paris Peace Forum (May 2021) and the fourth edition of the annual event (11-13 November, 2021).

Grants awarded from 1 October 2005 to 30 June 2021

Creative Commons Attribution 4.0 International (CC BY 4.0)


Discretionary Award - Policy

Panel on Financing for Pandemic Prevention, Preparedness and Response A new high-level panel, led by co-chairs Tharman Shanmugaratnam and Lawrence H. Summers, has been mandated by the Italian presidency of the G20 to propose reforms and other measures that will lead to more reliable and sustainable financing of pandemic prevention, preparedness, and response. To support the panel's deliberations and decision-making, CGD and Bruegel propose establishing a team to lead the analysis and content development of the proposals, with logistical, outreach, engagement, and coordination support from a secretariat at Wellcome and the US National Academies of Medicine. The team will develop a short scoping note on the economic rationale behind prioritizing public investment in prevention, preparedness, and response, an outline of the final report for discussion and feedback from the co-chairs, background analyses (on landscaping current financing and issues, existing asks and proposals; setting a financing goal and assessing its value for money; and governance, organization, and incentives), a long list of 10-15 proposals for governance reform and/or new or existing financing sources and mechanisms (with pros and cons for the panel's consideration), and a final report reflecting the panel’s views and the teams’ own analyses.


Discretionary Award - Vaccines

THE ARM RACE: HOW WE CONQUERED COVID (WORKING TITLE) "THE ARM RACE: HOW WE CONQUERED COVID" (working title) is a documentary film that will be the dispositive chronicle of the global race to research, develop, manufacture and distribute COVID-19 vaccines in the most enormous coordinated effort ever undertaken. In this unprecedented moment in history, the film will celebrate the herculean efforts of the scientific, research and immunization community during a complex time of mistrust, vaccine hesitancy, and misinformation - when trust in science itself has come under fire.

The stories track development of vaccines, (including research built on previous work fighting outbreaks including Ebola and HIV/AIDS,) and how public health agencies from hospitals to the WHO are responding to the crisis. Our narrative goes beyond the lab, delving into the complexities of underserved populations, equitable access and inclusion. We see opportunities in additional content, leveraging existing assets, foregrounding the making of the film and our collaboration with the global public health community. This project will spark interest in science’s potential to solve global health challenges by documenting the largest public health effort in human history, while also offering insights into our successes and failures to help prepare the next generation to better respond to future pandemics.


Discretionary Award - Mental Health

Can we develop a "cognitive vaccine" for intrusive memories of traumatic events from working in the COVID-19 pandemic? A novel and brief intervention to support ICU staff Intensive care unit (ICU) staff face repeated exposure to traumatic work-related events and have reported high levels of posttraumatic symptoms during the pandemic. Novel, scalable and preventative interventions are required.

We are developing a "cognitive vaccine" approach for ICU staff against one key symptom – intrusive memories of traumatic events. These are unwanted, distressing and disrupt functioning.

Our novel, brief gameplay intervention is repeatable, flexible, non-stigmatising, scalable, and driven by mental health science.

This digital intervention is guided by an initial session of psychologist support, then self-administered; delivered same day or months post-trauma, suitable for repeated trauma exposure, fits with busy lives of ICU staff, without discussing trauma detail.

Part 1 uses a Bayesian design to optimise and co-develop procedures with ICU professionals and move at speed under pandemic conditions, allowing limited rollout (guided-version) in these unprecedented times.

Part 2 uses a pragmatic RCT (three arms: guided/non-guided/attention-control) testing clinical effectiveness and acceptability to inform clinical practice. If the non-guided intervention is effective (i.e. no psychologist support) it will accelerate the speed of rollout.

Meanwhile through global mental health workshops with stakeholder communities we seek to understand the views of various communities worldwide regarding implementation of this novel intervention form.


PhD Studentship (Basic)

Combining computational structural biology methods to visualise the dynamics of cell-virus interactions at molecular resolution Archaea are single-celled organisms distinct from bacteria, but that share a number of traits. Like some bacteria, many archaea have a surface layer (S-layer) surrounding the cell, which is a proteinaceous lattice that helps protect the cell from attack from viruses. Understanding how the viruses bind to the S-layer will help us to understand how they infect the cells.

Using cryo-electron microscopy (cryo-EM), an increasingly popular technique for obtaining structural information about proteins, we will study a variety of archaeal S-layers and some of the viruses that infect them. This data will then be combined with molecular dynamics (MD) for a multiscale investigation of how these S-layer proteins move and interact over time.  By solving the structures of the S-layers using cryo-EM, then simulating the interaction of the proteins in the lattice using MD, we push method development to lead the way in cellular structural biology.

With this work we will develop the understanding of viral entry in archaea, and the structure-function relationship of S-layers which has implications on the evolution of life. Tomography will provide cellular context to structures, and direct the large-scale MD simulations, built up from smaller simulations of atomic structures solved by cryo-EM.


PhD Studentship (Basic)

Novel allosteric modulators of nicotinic acetylcholine receptors implicated in cognitive dysfunction  Nicotinic acetylcholine receptor (nAChR) subtypes such as alpha7 and alpha4beta2 have been implicated in a range of psychiatric illnesses, including schizophrenia and Alzheimer’s disease. During the past two decades, the identification of multiple nAChR allosteric modulators (drugs that alter the response of a receptor to its natural agonists) have attracted significant interest. A recent study conducted in this laboratory reported an in silico screening of the DrugBank database against a predicted alpha7 nAChR allosteric site. Amongst the compounds identified in this study, the Na-K-Cl cotransporter inhibitor furosemide was found to be a potent positive allosteric modulator (PAM) of the alpha7 nAChR in electrophysiological assays. The objective of the present project is to expand on our understanding of how the chemical composition of allosteric modulators such as furosemide and its structural analogues influences their allosteric modulatory properties at nAChRs subtypes such as alpha7 and alpha4beta2. I will attempt this via the synthesis of a library of novel compounds (including furosemide analogues). Subsequent electrophysiological and computational (e.g. computer docking) studies of these compounds with respect to their allosteric modulatory activity at the alpha7 and alpha4beta2 nAChRs will be undertaken with the aim of developing a clearer understanding of their structure-activity relationship.


iGEM competition 2021

Strategic Support: Science

iGEM competition 2021 This grant will support the 2021 International Genetically Engineered Machine Competition (iGEM), by supporting UK undergraduate students from the synthetic biology community to take part in it.
The provided funding will be used to support the students’ stipends, some consumable and travel support for the teams that have successfully applied to the competition.
Wellcome has funded the iGEM programme for several years as this is an interesting model to develop interdisciplinary thinking and skills for students. Funding is provided in partnership with BBSRC who also make available a £50k contribution.
Wellcome (Luigi Martino) will be involved at the selection stage and receive a brief report about the respective activities at the end of the year.

COVID-19 effect on the competition. The hope is that this year’s teams will have the ability to undertake wet-lab-work. If this is made impossible by the potential restricted access to lab spaces, the selected teams will be asked to submit a written proposal reporting the design and strategy to build their chosen genetically engineered machine.


Discretionary Award - Policy

Emergency Efforts to Sustain UK Government Support for ODA In the 2020 Spending Review HMG signaled its intent to renege on a manifesto commitment and cut ODA form 0.7 to 0.5% of GNI (on top of the budget cut that happened automatically due to economic contraction). To do this, HMG wishes to repeal the relevant in coming months.

Work to sustain the Government’s support for ODA is already delivering results with an increasingly credible threat of a government rebellion and sustained media interest. However, increasingly our political intel says we may be at risk of winning the vote and losing the argument. Put simply, ‘hard whipping’ of a rebellion, combined with some horse-trading between different groups, might be enough to carry a vote but it won’t stop the debate flaring back up. This grant would allow us to scale the emergency effort around the legislation while also creating a more enabling environment for the longer team:

 by bolstering our public affairs capability in Qs 1/ 2,
 by expanding our local organising effort to an additional ten constituencies from Q1-4 and
 by expanding our comms plans from Q1-4.

A key part of this partnership would be Wellcome’s inclusion in regular political updates, intel and learning sessions.


PhD Studentship (Basic)

Targeting individual bromodomain and extra terminal domain (BET) proteins (BRD2-4) to modulate breast cancer angiogenesis Tumour cells requires oxygen and nutrient to grow. As tumours outgrow their existing blood supply they develop regions that have low oxygen (hypoxia) and nutrient levels. These regions are often found in breast cancer and they are associated with resistance to chemotherapy and radiotherapy. Cancer cells exposed to low oxygen release chemical signals that stimulate the growth of new blood vessels which can then deliver the required oxygen and nutrients. There are four Bromodomain and extra terminal (BET) proteins that bind to sections of the DNA that has been chemically modified to indicate if a gene should be active or inactive. The BET proteins then recruit other proteins which are important for transcribing genes. It has been shown that drugs that inhibit the BET proteins change how the cells respond to hypoxia and reduce the growth of new blood vessels.
I will investigate how the BET proteins regulate the growth of new blood vessels and identify which of the four BET proteins is the best target for new therapies. Regulating blood vessel growth can lead to the reperfusion of tumours and allow radiotherapy and chemotherapy to effectively treat patients with solid tumours.


PhD Studentship (Basic)

A GWAS of the progression of abdominal aortic aneurysms and simultaneous use of genetic and non-genetic information in the evaluation of screening and diagnostic testing pathways In the UK, men aged 65 are invited to screening to check for an Abdominal Aortic Aneurysm (AAA).  Untreated aneurysms may rupture, which is usually fatal, although many aneurysms do not progress to this stage.  There are known risk factors for AAA such as smoking and family history.  Evidence of genetic association with AAA has been found which means that some people are more at risk from birth of having an aneurysm.

I plan to investigate the role of genetics in both the presence and progression of disease, utilising data from UKBiobank, the UK Aneurysm Growth Study and AAA-Express.  These findings will be adopted into a hypothetical computer model.  I will investigate the possibility of targeted screening for AAA. This involves identification of risk factors that will also consider the benefit of genetic data to identify individuals at high risk of AAA for screening invitation. I will then investigate an adapted clinical pathway after detection of aneurysm based on the risk of rupture. Incorporating genetic information may improve patient outcomes and the cost-effectiveness of the screening program by limiting screening to those most at risk and by ensuring that those diagnosed with an aneurysm have the most appropriate clinical intervention.


PhD Studentship (Basic)

Assessing the contribution of common and rare short tandem repeats (STRs) to the risk of developing idiopathic pulmonary fibrosis (IPF). Idiopathic Pulmonary Fibrosis (IPF) affects around five people in every 100,000 in the UK and is amongst the most devastating of lung diseases, with a median survival time of 3 years and variable progression. Comparable disease prevalence (6.8 per 100,000 persons) has also been reported in other countries such as the USA, Italy, and Canada. About 5000 cases are detected annually in the UK, and there is rising disease prevalence globally. Despite the substantial disease burden, there is little understanding of the disease etiology, and it has a poor prognosis. Other than a lung transplant, the available drugs are not curative. The majority of cases are diagnosed in patients  > 50 years and males are disproportionately affected than females. Both genetic and environmental factors have been associated with IPF. The genetic mutations described so far only account for about 19% of genetic risk associated with IPF. Therefore, the analysis of other types of genetic variations is pertinent. In particular, our study will use whole-genome sequences in case-control cohorts to identify other genetic mutations associated with IPF susceptibility. Identifying risky mutations can help understand disease etiology and develop more targeted therapies.


PhD Studentship (Basic)

Understanding the genetic basis of radiotherapy toxicity Patients differ in the way they respond to radiation treatment.  Approximately 5% of patients are sensitive to radiotherapy and at risk of suffering long-term side-effects (1). However, there is no effective way to identify these patients. The REQUITE trial was established with the aim of reducing long-term side-effects from radiation (2). A total of 4438 cancer patients were enrolled in the study. Before receiving radiotherapy, patients completed a questionnaire and provided a blood sample which was analysed for genetic variants.
The researchers tested for other biomarkers that might predict sensitivity to radiation. One example includes the radiation-induced cell death assay called RILA. This is a measure of the percentage of white blood cells that are killed by radiation (3). The researchers found that a low RILA score is associated with long-term side-effects.
My research aims include finding possible genetic associations with the RILA assay. In addition to finding possible genetic associations to predict late side-effects in breast cancer patients and a genetic study on patient reported outcome measures such as quality of life scores. The overall long-term goal of this project is to integrate biomarkers, genetic and clinical data to help predict which patients will suffer from worse side-effects.


PhD Studentship (Basic)

The genetic epidemiology of lung scarring Idiopathic Lung Fibrosis (IPF) is a disease which leads to death three years after diagnosis in half of cases. IPF is a complex genetic disease - variants of DNA that contribute to disease risk have been identified, though we have yet to fully understand how these risk factors lead to lung scarring.

A Genome-Wide Association Study (GWAS) can be used to determine which regions of DNA are associated with disease.  GWAS can be used to look at individual variant sites in the DNA called Single Nucleotide Polymorphisms (SNPs).  By comparing the entire DNAs (Genomes) of people with and without IPF, we can narrow down the suspected sequences that may contribute to the development of the disease to very fine resolution.

Once SNPs associated with IPF are identified, we then need to understand why they are associated. Determining which SNP leads to IPF requires 1) Linking SNPs to genes, 2) finding biochemical pathways associated with these genes, and 3) finding drugs that can be used to target the biochemical pathways. These steps enable us to understand the pathology of IPF and could lead to the identification of potential drug treatments for this currently incurable disease.


PhD Studentship (Basic)

Must the relatives be told? Legal and ethical issues in relation to the non-disclosure of genetic information by healthcare professionals to relatives Genetic information is becoming increasingly utilised by healthcare professionals in order to provide patients with more precise diagnosis and treatments. An individual's genetic information may show their risk of inheriting a genetic disorder, and although most individuals would consent to healthcare professionals sharing their genetic information with relatives who may also be at risk, some individuals refuse. It can be argued that a failure to disclose the risks of inheriting genetic disorders to relatives is ethically wrong, because it restricts the autonomy of individuals to make life choices. Alternatively, it can be contended that it is legally wrong for a healthcare professional to not adhere to the duty of confidentiality that they owe to patients.

This debate demonstrates the conflict of duties that healthcare professionals face as the use of genetic information in medicine develops, and highlights the need to develop a new legal  framework which takes into account the needs of patients, relatives, and healthcare professionals. In order to create an appropriate legal framework, I aim to assess academic commentary, examine case law, and conduct qualitative interviews with healthcare professionals in order to assess scientific opinion, and potentially inform new policy guidance.


PhD Studentship (Basic)

Synthesis and evaluation of novel antagonists and fluorescent ligands for the human P2Y2 receptor The human P2Y2 receptor is one of a large and diverse family of disease-relevant drug targets called G protein-coupled receptors. The P2Y2 receptor is a promising therapeutic target for important conditions, including metastatic cancer. However, no drugs which block the P2Y2 receptor have ever entered clinical trials.

The research group recently published an initial study where novel P2Y2 receptor inhibitors, that prevent the action of the receptor, with good biological activity were produced. The project will build on this previous work to design, synthesise and evaluate further inhibitors with improved biological activity and drug-like properties to make them more clinically viable. The design of these inhibitors will be driven by visualisation of key interactions with the P2Y2 receptor in computational models. Another subsequent part of the project will involve equipping these novel inhibitors with a light emitting fluorescent dye that can be used to investigate their interaction with the P2Y2 receptor in cell and tissue-based experiments with state of the art imaging equipment.

Novel, high affinity and drug-like P2Y2 receptor inhibitors and their fluorescently-labelled counterparts would provide a vital tool to further validate the role of P2Y2 in disease and aid in the development of clinically viable drugs.


Discretionary Award – DSH

Learning Data Driven Medical Checklists For Multi-Disciplinary Consult Scheduling Checklists are simple tools that are often used to promote safety in clinical applications, because they can easily be integrated into a clinical workflow deployment without the need for extensive training or additional technology. Currently, machine learning in health focuses on large, complex deep neural networks. In comparison with deep neural networks, checklists are far easier to use, understand, and scrutinize. In practice, checklists are difficult to develop, and the vast majority of real-world checklists are hand-crafted by panels of experts.

Given the widespread integration of electronic health data over the past decade, our goal is to learn checklists from data for clinical tasks. The main application of our method, in partnership with Dr. Leo Celi at Beth Israel Deaconess Medical Center (BIDMC) in Boston, is to predict mortality in patients eligible for Continuous Renal Replacement Therapy (CRRT).

A generated checklist for CRRT is clinically desirable in the intensive care unit as a mechanism to trigger a multidisciplinary discussion with the patient’s family, to consider the value of the treatment weighed against the physical burden and cost. Thus we include operational considerations such as number of items in the checklist, the false negative/positive rate tradeoff, and fairness across protected groups.


PhD Studentship (Basic)

Liquid-phase Transmission Electron microscopy of RNA polymerase dynamics Proteins control most cellular functions, made possible by their unique and diverse range of 3D structures and the dynamics within them. Methods to determine protein structure have revolutionised the understanding of cell function and dysfunction on the molecular level as well as drug design, however, these methods generally require static molecules. One rapidly developing method to probe protein structure uses transmission electron microscopy to take highly magnified images of cryogenically frozen proteins which can be computationally combined into a 3D model, however, freezing the sample prevents any real-time dynamics. We aim to optimise this method with new liquid-phase transmission electron microscopy technology, to film and understand structural dynamics of proteins in real-time in solution. This will require the development of electron microscopy techniques to image the protein clearly, image processing techniques to analyse the movies taken and molecular dynamics to understand and verify the results seen. We, therefore, aim to develop liquid-phase transmission electron microscopy as a technique to probe protein dynamics in solution, allowing the study of protein function, dysfunction and dynamic responses to stimuli, for example, drug binding. This will focus on RNA polymerase as a model system with physiologically relevant dynamics.


PhD Studentship (Basic)

Structural and mechanistic investigations of the SWI/SNF chromatin remodeller Packaging the two metres of chromosomal DNA found in every human cell is achieved by wrapping DNA around histone proteins in complexes called nucleosomes. Generally, DNA wrapped within nucleosomes is rendered inaccessible to enzymes and DNA-binding factors involved in normal DNA processes such as gene expression, DNA damage repair and chromosome replication. Chromatin remodellers are large molecular machines that disrupt the interaction between DNA and histones, exposing the DNA and therefore making it accessible for fundamental biological processes. I will be focussing on a particular chromatin remodeller called SWI/SNF that uses chemical energy to move, modify and eject nucleosomes. Around 20% of human tumours have been shown to have mutated SWI/SNF, highlighting the complex as one of the most commonly affected targets in cancer. The aim of my project is to use structural (cryo-EM) and single molecule (FRET) analysis to probe the molecular details of the interaction of SWI/SNF with the nucleosome. Moreover, we will visualise SWI/SNF in action, in an attempt to understand how the machine remodels nucleosomes and leading to further understanding of its role in cancer. Our results will provide a platform for the future development of drugs that specifically target mutated SWI/SNF complexes in numerous cancers.

Grants awarded from 1 October 2005 to 30 June 2021


PhD Studentship (Basic)

Structural Investigations of Sodium Channel Mutations Associated with Neurological Diseases Sodium channels (Navs) are proteins which are found in cells around the body, including the central and peripheral nervous system and heart muscles. These proteins span the cell membrane and form channels which specifically allows sodium ions to cross the membrane under certain conditions. This influx of sodium ions in neurons is responsible for information processing and is critical for nervous system function. Genetic mutations in Navs can cause multiple diseases including epilepsy, chronic pain and cardiac arrhythmias. Generally, these mutations reduce the function of Navs, disrupting the balance of information, for example in the brain sometimes resulting in epilepsy. Specific drugs therefore need to be developed in order to re-establish this balance either by adding to Navs’ functionality or reducing it. We aim to use structural biology techniques, including x-ray crystallography and potentially cryo-EM to visualise potential drug binding sites. We will also look at common disease-causing mutations allowing us to identify drugs which will not only target a specific subtype of Nav but also a specific mutation. In particular we will be looking at repurposing already commercially available drugs. This work has the potential to identify drugs for Nav related diseases and provide new treatment options for patients.


PhD Studentship (Basic)

Generative models for biological methods of control Behavioural phenotypes are highly relevant to many diseases, particularly those involving neurodegeneration, such as Friedreich’s Ataxia or Parkinson’s disease. While these behavioural phenotypes arise from low-level molecular and cellular processes, they are highly complex. As a result, identifying structure within behavioural data can be challenging. Generative models are a type of model which are able to generate new instances of data, unlike discriminative models which can only discriminate between existing instances. As a result, these models must solve the more complex problem of whether a given data instance is likely, as opposed to what classification it most likely belongs to. This means they must learn the underlying distributions of the data itself, often capturing more meaningful correlations as a result. Building generative models of behaviour can therefore offer deeper insight into the structure of behaviour, as well as a means of analysis through synthesis, where the ability of a model to successfully reproduce naturally observed behaviour provides further validation of the model. These models can also be used to investigate the impact of disease on behaviour through attempts to ‘corrupt’ the model’s underlying processes and compare the output to experimental data obtained from individuals with a particular disease.


UCH photography exhibition

Discretionary Award – Directorate

UCH photography exhibition Produce, print and install an exhibition of photographs by Tom Pilston documenting University College Hospital (UCH) staff working on the Covid pandemic.  Exhibtion to be in UCH lobby in Euston Road


Innovations AIGH Enterics Flagship

Advancing product development and use of monoclonal antibodies for infectious disease in low and middle income countries (LMICs)’ The project supports activities in the Immunization, Vaccines and biologicals
department of the WHO that aim to advance the product development and use of
monoclonal antibodies (mAbs) for infectious diseases, with a focus on meeting the
needs of Low and Middle Income Countries (LMICs). Three specific activities will be
carried out. First, a stakeholder consultation on monoclonal antibody technologies will
be held to discuss which would best support affordability and accessibility in LMICs.
Second, an application to establish rabies mAbs on the WHO model list of essential
medicines (EML) would set the precedent for inclusion of additional infectious diseases
mAbs in the future. Thirdly, an assessment of diphtheria immunoglobulin supply and
potential demand for mAb-based products will be carried out which could serve as a
methodology to be used to assess other mAb based products."


Research Development Award in H&SS

Doing natality: making babies, making kin in Africa Africa has the fastest growing population in the world. At the same time the continent has some of the highest rates of infertility. Most people long to have children for diverse reasons. Those unable to have children seek ways to improve their chances of conceiving. These may include biomedical interventions, vernacular healing practices, changing or adding partners or making kin through adoption and child circulation. Yet despite the diversity of lived experiences and practices of reproduction across the continent, most research and interventions into reproductive health in Africa frame it primarily in terms of risk, pathology, mortality, and irresponsibility. Doing Natality engages a team from four African countries, working across demography, social sciences, medical humanities and science and technology studies, to develop a research agenda that centers the notion of "doing natality". We aim to explore practices of doing natality as articulation of love, care, beginning something new and securing better futures in raising children. We thereby open up a new space to interrogate and explore the usefulness of the notion of "doing natality" as heuristic, theoretical and methodological tool by asking what it means for African women, men and couples to have (or not have) children.


Research Development Award in H&SS

Setting an Emancipatory Agenda: Disabled People's Research Network Social science research has long been criticised for failing to improve the life chances of disabled people. Current research agendas are determined ‘top down’ by policy makers, and researchers risk objectifying disabled participants by conducting research ‘on’ them (as opposed to ‘with’ them). Our radical and exciting proposal challenges the status quo by developing an inclusive agenda and establishing a Disabled People’s Research Network. Our vision is to place academic and non-academic disabled people at the heart of research development, and our entire project will be co-produced by working with disabled people’s organisations. Our activities will identify new salient questions and reinvent social science methodology by exploring how the arts and humanities can enable disabled people to evidence and share their lived experiences. We will develop more inclusive forms of knowledge exchange between universities and disabled people, and we will work with policy makers to maximise disabled people’s research impact. We will empower disabled people as agents of change and our activities will include a range of fellowships for disabled people and a highly innovative research training course led by disabled people. Our network will reinvent how universities work with disabled people, in addition to methodological and epistemological development.


Research Development Award in H&SS

Dr Clare Barker, Mrs Faye Robinson, Dr Amelia DeFalco, Dr Tom Jackson, Prof James Stark

LivingBodiesObjects: Technology and the Spaces of Health LivingBodiesObjects is an experiment in the making and understanding of interactions between bodies, technologies, objects and health, designed to test and extend the boundaries of Medical Humanities research. Working with a range of partners, it will take place in the context of multi-purpose/use laboratory spaces (both physical and virtual) that invite differing conceptions and practices of health experiences, and responses to them. The ambition of the project lies in the imaginative creation of these spaces and not in any pre-emption of the materials they might produce. The laboratories will be specifically designed to figure ideas and creativity, making spaces that provoke, facilitate and respond to the ideas and questions raised by bodies as they encounter different forms of technology.  Centring on the ways in which individuals and communities collaborate to produce work within dynamic and generative locations, the laboratories will also link to more traditional laboratory activities such as equipment, testing and use. As a specific research development initiative, the project will further extend interdisciplinary health research practice at the University of Leeds, where its work will inform and further develop a research culture through the foregrounding of innovation in professional research management, career development and equality, diversity and inclusion.


Centre for the Social Study of Microbes

Research Development Award in H&SS

Centre for the Social Study of Microbes The aim of this Research Development Award is to establish a leading centre for the social study of microbes. Since their discovery, microbes have been predominantly defined as pathogenic and threatening to human and animal health. Recently, however, societal, and scientific views about microbes, immunity, and antibiotics have started to acknowledge the beneficial and symbiotic qualities of bacteria, viruses and fungi. Existing social scientific language is insufficient and outdated in describing the complex and entwined relationships between humans, nonhumans, microbes, and environments. These relations with microbes raise profound challenges for the foundations of social theory.

Strategically situated within an emerging network of research, this application will establish an egalitarian and experimental research infrastructure to develop new social scientific concepts and methodology to address the challenge. The Centre will host international research fellows and an art residency, and organise social theory and methodology workshops, two academic seminars annually, and a yearly PhD Summer School to support younger generations of scholars. Not only is this work theoretically essential, it is also key to understanding and acting upon the way humans relate to microbes and other nonhumans, a vital objective for developing sustainable ways of planetary co-existence.


Leaving no-one behind in Research

Research Development Award in H&SS

Leaving no-one behind in Research Three paradoxes in global research ethics seriously harm vulnerable populations.

First, health research works. Yet, to protect vulnerable populations from exploitation, they are often excluded from it.

Second, international collaborative research works. Yet, major trust issues block collaborations with vulnerable populations who have previously been exploited.

Third, the further apart researcher and end-user experiences are, the more urgent the co-creation of research becomes. Yet, successful co-creation methods for non-clinical health research with vulnerable populations in low and middle income countries (LMICs) barely exist.

All three paradoxes restrict non-clinical health research in LMICs.

Leaving no one behind in research will build an extensive research agenda to tackle all three paradoxes by:

 radically rethinking the concept of vulnerability and what appropriate protection mechanisms for the vulnerable would look like.
 enabling indigenous peoples and sex worker teams to define what vulnerability means to them and how they want to be protected in research.
 developing a humanities method for non-clinical health research that would make research less risky for vulnerable populations.

The above will be achieved by a highly-experienced research leader and her UK team in a network with two African teams representing vulnerable populations.


Research Development Award in H&SS

Dr Emmanuel Tsekleves, Prof Elena Semino, Dr Kirsty Dunn, Prof Sharon Ruston, Prof Sara Fovargue

The Future of Human Reproduction: transformative agendas and methods for the Humanities and Social Sciences New and emerging reproductive technologies have the potential, within a generation or two, to profoundly disrupt established social practices linked to human reproduction and parenting, as well as the concepts of relatedness and family.  Better understanding the cultural, ethical, legal, and social issues that this prospect raises is the principal substantive research aim of this programme.  We will examine three such technologies.

Ectogenesis could allow us to develop fetuses wholly outside the body, to create children who have not been ‘born’ (in the usual sense of that term).

Genome editing will mean that future children can be ‘chosen’ or ‘designed’ with far greater levels of precision than at present.

New methods of creating eggs and sperm will enable the creation of children with two genetic parents of the same sex, or who have multiple genetic parents, or perhaps no determinate genetic parents at all.

Using these cases as focal points, we will develop transformative new research methods and modes of interdisciplinary working - for example, by integrating speculative design methodologies with those of bioethics, law, literature, linguistics, and psychology.  Our ultimate aim is for this to lead to a novel research paradigm for the study of disruptive emerging technologies.


A new voice for R&D investment

See attached document.

Discretionary Award - Policy

A new voice for R&D investment See attached document.


PhD Studentship (Basic)

Enhanced analysis of microscopy images using deep learning: applications to histopathology of ovarian cancer Single Molecule Localisation Microscopy (SMLM) has enabled scientists to observe biological processes at a molecular level. These techniques typically generate 3D point cloud data which localise individual molecules within the specimen. The spatial statistics of these point clouds have then been used to classify, segment or co-localise molecules to support hypotheses regarding the underlying biological processes occurring in the sample. As this is currently achieved through non-deep learning approaches (eg: Ripley's functions, DBSCAN, graph based or shallow neural networks), I will investigate the applicability of existing deep learning solutions on SMLM point cloud data. From this set of existing work, I will design and evaluate possible improvements to these systems. Improvements in the performance of these models could provide better acuity in the post-processing of SMLM images, and thereby improve our understanding of the fundamental biological processes involved.


PhD Studentship (Basic)

Adaptive motor learning through systems-level modelling of neural populations The brain can learn a variety of motor skills, from using chopsticks to playing the piano. Some skills are easier to learn than others, and this may be affected by the skills that you already have.

We are interested in how motor learning occurs in populations of neurons. Networks of neurons work together to produce different neural activity patterns that drive learning and movement. The possible patterns that can be produced thus depend on the structure of the network, and this can be affected by existing skill sets.

We will use artificial neural networks to computationally model motor learning. We will train the model on different motor tasks and see how they adapt to learning new ones. This will be coupled with experimental data that measure neural activity in monkeys and mice during motor tasks. By understanding how the brain learns new movements, we can gain insight into applications of assistive devices and therapies for motor function.


PhD Studentship (Basic)

A novel anti-tumour tri-specific engager to promote T cell and NK cell activation within the tumour microenvironment  Antibodies are proteins, naturally produced by the immune system, that bind other molecules. This interaction can block the function of the bound molecule and is exploited in anti-tumour treatments. For instance, antibodies can block immune inhibitory receptors. These receptors are responsible for stopping the immune system from killing infected cells and cancer cells. For various reasons, some cancer patients do not respond to treatments with antibodies. Some can be attributed to the relatively large size of antibodies and the presence of immune inhibitory molecules within the tumour.

The aim of our project is to develop a new anti-tumour treatment to unleash the capacity of the immune system to attack and kill cancer cells. Our goal is to use genetic engineering to design small antibody proteins that can bind more than one distinct immune inhibitory receptor simultaneously. By doing this, we aim to restore the natural ability of the patient to recognise and eliminate tumour cells.


PhD Studentship (Basic)

Inferring structural properties of the myocardial substrate from multipolar electrogram recordings using deep learning The contraction of the heart muscle is caused by the propagation of electrical signal throughout the heart. This signal is propagated from cell to cell through proteins called ion channels and gap junctions. Physiological and pathological heterogeneities and changes in the expression of these proteins, result in the conductivity field of the heart tissue being non-homogeneous and anisotropic. This can result in electrical waves that propagate abnormally and can cause atrial fibrillation, which is an irregular beat in the upper chambers of the heart, the atria, and one of the most common cardiovascular diseases.

The aim of this project is to test the hypothesis that data from electrograms, recorded by electrodes in direct contact with the heart, can be used to estimate the conductivity field of the cardiac tissue. Deep learning methods will be used to solve this inverse problem, first applied in synthetic data, and then validated in a biological setting.

By reconstructing the conductivity field of the heart muscle from electrograms, the currently-low success rate of the treatment of atrial fibrillation through ablation will be increased, since the clinicians will have a better indication of the position of the low-conductivity tissue that has to be ablated.


PhD Studentship (Basic)

Determining the roles of the Artemis nuclease in genome stability at the replication fork Damage to DNA occurs constantly within our cells. If this damage is not repaired, it can lead to mutations in our genome when cells divide, which can cause cancer. So, to protect the integrity of our DNA, cells have evolved a variety of mechanisms to fix these lesions.

One protein that plays a key role in these processes is Artemis, which acts in the repair of several different forms of damage by incising sections of damaged DNA. I will study this protein using a range of biochemical, genetic and cell biology techniques. These will characterise the reactions that Artemis catalyses at sites of DNA damage, whether it requires interacting partners or modifications to do so and will enhance our understanding of the functions of each of its domains. I will also be collaborating with chemists to develop inhibitors against Artemis.

By better understanding the mechanisms that protect our DNA at the molecular level, we can improve cancer treatments. Chemotherapeutic drugs often kill tumour cells by damaging their DNA and cancers can evolve resistance to these treatments by increasing their capacity for repair. Inhibitors targeting Artemis could therefore be used to help overcome resistance to chemotherapeutic drugs and radiotherapy.


PhD Studentship (Basic)

Dissecting structural and functional contributions of promoter interactions in gene regulation Understanding how complex multicellular organisms, made up from trillions of cells within multiple tissues, develop from a single fertilised egg requires turning specific genes on and off at the right place and time, in a pre-determined order. The entire process is encoded within the DNA sequence of the genome in each individual cell. In humans, there are about 20,000 genes, which encode functional units such as enzymes or haemoglobin, but these only constitute 1-2% of the DNA sequence in each cell. The DNA also contains surrounding regulatory elements that control the output of genes. There are 3 classes of such elements: promoters, enhancers and boundary elements. It is becoming increasingly clear that the roles of these elements overlap one another.

In this work, I will study the characteristics of promoter interactions and the resulting impact on gene regulation. I will be particularly interested in how promoters control gene expression by changing the three-dimensional architecture of the genome as well as the conditions by which promoters interact with enhancers. Ultimately understanding the process of gene expression will enable us to understand how these genes are normally switched on and off during development and how this goes awry in human disease.


PhD Studentship (Basic)

Mechanisms of RUNX1 regulation in human developmental haematopoiesis and childhood leukaemia All adult blood cells are derived from prenatal blood stem cells produced in the embryo, where the process is dependent on a gene named RUNX1. Blood cell formation and the development of various blood cancers (leukaemia) are sensitive to RUNX1 levels. In my DPhil, I will characterise the mechanisms regulating RUNX1 levels in normal and malignant human blood cell formation. I will use a "test tube" experimental approach to model human fetal blood cell formation, by differentiating stem cells into immature blood cells (progenitors). I will characterize the dynamic regulatory changes in the RUNX1 genomic region at distinct blood progenitor stages. These data will form the benchmark for the examination of RUNX1 regulation in primary human blood progenitor cells and childhood acute lymphoblastic leukaemia (ALL) samples. Lastly, RUNX1 regulation will be perturbed through genetic and epigenetic engineering, to identify the contribution of aberrant RUNX1 expression to the development of childhood leukaemia. This comparative approach will help us understand not only regulatory mechanisms of normal human blood cell formation, and how well this process can be modelled in a test tube, but also how altered regulation of RUNX1 affects leukaemia development.

Precursor Cell Lymphoblastic Leukemia-Lymphoma


PhD Studentship (Basic)

Mechanisms of Transcriptional Regulation by H3K4 Methyltransferases at CpG Islands The genetic information of each cell is stored in the nucleus as DNA wrapped around histone proteins, a structure termed chromatin. Apart from packaging DNA into the confined space of the nucleus, histone proteins serve as a template on which chemical modifications can be placed. These modifications can determine whether the associated gene is actively being used to produce messenger RNA (mRNA) and subsequently its product. I am studying the four ‘writers’ of one such modification, tri-methylation of lysine 4 on histone H3 (H3K4me3). These four enzymes, SET1A, SET1B, MLL1, and MLL2, have major roles in activating genes, but they seem to do so in a way that is separate and distinct from their roles as the writers of this modification. To understand how these enzymes activate genes, I am using genetically engineered cells in which these enzymes can be rapidly degraded by treating the cells with a small molecule. By removing these enzymes separately and in combination, I can analyse how these enzymes contribute to the overall levels of mRNA and H3K4me3 of the cell using sequencing techniques. The results of this project will be expected to increase our understanding of how genes are activated.


PhD Studentship (Basic)

Development of pathway-based predictive models and their use in multi-omics clinical studies As the field of systems biology continues to develop, huge volumes of molecular data are being generated, including 'omics' data which aims to characterise activity at various levels of the biological system, such as genomics, transcriptomics, and metabolomics. A key challenge is the integration of multiple omics datasets to obtain a more holistic understanding of how the layers of the biological system work together. Pathway analysis is a method for assigning molecular entities to their respective biological pathways, to better facilitate biological interpretation of omics data. Current tools for the integration of multi-omics data focus on integrating the data at the level of individual molecules. However, the integration of omics data at the level of biological pathways has not yet been investigated. As biological entities are known to interact within pathways, I propose the development of a novel method for combining multi-omics data by integrating the layers at the pathway level using statistical/machine learning approaches. This work will result in novel methods researchers can use for integrating omics data at the pathway level, with a focus on improving interpretability, sensitivity (the ability to detect biological signals), and predictive ability (using the model to predict e.g. disease status) of current methods.

Grants awarded from 1 October 2005 to 30 June 2021


PhD Studentship (Basic)

Electrical stimulation for chronic diabetic ulcers healing  Wound healing is a complex process wherein the tissue undergoes inflammation, repair and maturation to re-establish initial equilibrium. When transition between the stages fails, the tissue remains stuck in an inflammatory state, deferring healing and greatly increasing the probability of systemic infection, which may lead to member amputation or even death. Chronic wounds are prevalent in diabetic patients and represent an individual as well as a societal financial burden. Despite of this, it is still unclear how to robustly regulate the process to exit the chronic state and few advanced therapies show evidence of improving the outcome compared to standard treatment. Electric stimulation (ES) is a promising non-invasive procedure that was shown to influence the behaviour of the cells leading the immune and repair response to skin damage. ES was shown to modulate  exchange of calcium whose changes in level are correlated with wound stages. The project aim is to define effective time dependent ES regimes that promote the healing of diabetic ulcers by characterizing normal and diabetic-derived cells and their response to ES. Furthermore, calcium signalling will be investigated to reveal ES mechanisms driving cellular response.


Prof Clare Mackay, Dr Shaihan Malik, Prof Lawrence Wald

Sir Henry Wellcome Postdoctoral Fellowship

Next-generation diffusion MRI: Illuminating the black holes of the brain  A major challenge in establishing novel therapeutics for neurological diseases is the assessment of tissue health. The inaccessibility of the brain for biopsy has motivated the development of novel technologies, with diffusion Magnetic Resonance Imaging (MRI) emerging as one of the most promising techniques to non-invasively assess brain tissue. Diffusion MRI generates images sensitive to the microscopic motions of water within and around cells. It has demonstrated considerable potential to identify novel biomarkers in a number of neurological diseases.

Despite this promise, conventional diffusion MRI methods have failed to access certain key brain regions. In these regions, rapid signal-decay (short-T2) leads to low-quality images with the appearance of ‘black holes’. I propose to establish an imaging platform that enables us to assess tissue health in these previously inaccessible regions. I will achieve this using a little-known but powerful technique, ‘steady-state diffusion’.

Building on a framework I have recently developed, I will:

 Transform steady-state diffusion images into those with clear biological interpretation.
 Enable in vivo use by overcoming its extreme motion-sensitivity.
 Reduce examination times by integrating the estimation of signal dependencies.

Utilising this platform, I will investigate the substantia nigra, a black hole brain region of critical importance in Parkinson’s disease.


Dr Venizelos Papayannopoulos, Dr Simon Elsässer

Study of the dark proteome in innate immunity Intrinsically disordered proteins/domains (IDPs/IDRs) are highly flexible and lack a defined secondary or tertiary structure. Their highly reactive and versatile interaction surface contains diverse small linear motifs that enable IDP/IDRs to act as key regulatory protein interaction and signalling hubs. In addition, a new set of small proteins have recently emerged by the identification of thousands of microproteins or smORF-encoded peptides (sPEPs) from which a few validated sPEPs play crucial regulatory roles via protein-protein interactions and add a new regulatory dimension to multiple cellular processes. Due to the size of sPEPs and high flexibility of IDPs, conventional tagging, biochemical and cell biological approaches are not suitable for the study of these type of proteins. I will overcome this by implementing a pipeline to achieve the orthogonal site-specific incorporation of minimally invasive non-canonical amino acids in IDPs and sPEPs. With this approach I aim to study the protein-protein interaction networks, localization and function of IDPs and sPEPs involved in innate immune processes such as the antiviral response or neutrophil defense mechanisms against pathogen invasion.


PhD Studentship (Basic)

Exploiting SUMOylation to target MYC-driven cancers MYC is a protein which is known to contribute to the development of cancer. It is found in many different types of cancer cells at much higher levels than it would be in healthy cells. As a result, MYC has been identified as a protein that could be targeted to treat cancer patients. However, developing a drug that inhibits MYC directly has proved challenging. Therefore, scientists have instead focused on targeting MYC indirectly. For example, several genes have been identified that when inhibited, result in the death of only cells that have too much MYC, such as cancer cells. This means that healthy cells with normal levels of MYC will not be affected. An example of one such gene is SAE2. SAE2 is an enzyme which catalyses the first step in a series of reactions called the SUMOylation pathway. Although this is an encouraging observation, it remains unclear why inhibiting SAE2 kills cancer cells with too much MYC. Therefore, the aim of my project is to find out why and how SAE2 inhibitors kill these MYC-overexpressing cancer cells. This will help determine whether we can use SAE2 inhibitors to treat cancer patients whose tumours possess too much MYC.


Neuronal identity and numbers in the development of neocortical activity The function of the cerebral cortex relies on the cellular balance between excitatory (pyramidal cells) and inhibitory neurons (interneurons), which is disrupted in disorders such as autism or schizophrenia. The emergence of cortical function relies on spontaneous synchronous activity among large groups of pyramidal cells and interneurons, which later desynchronize for efficient information processing. Prior to this shift in network activity, interneuron numbers are adjusted through activity-dependent programmed cell death mechanisms. The contribution of interneuron programmed cell death to the change in network dynamics and the identity of the cell types participating in these events remain unclear. I will address these questions by combining in vivo longitudinal functional imaging of the postnatal somatosensory cortex with cell type identification via multiplex in situ RNA localization. This strategy will allow correlating the identity of one neuron with its activity pattern and participation in network dynamics during early postnatal development. I will perform complementary experiments in mouse models engineered to contain abnormal numbers of cortical interneurons, thereby assessing the importance of neuronal numbers for cortical function. This project addresses the fundamental question of how neuronal diversity and numbers contribute to the emergence of functional circuits during physiological and pathological brain wiring.


Prof Surya Ganguli, Prof Timothy Behrens

Principles behind neural representations in complex tasks Generalisation is central to intelligent behaviour. Recent work has shown the classic dichotomy of hippocampal function, relational memory and spatial cognition, can be unified through the language of generalisation. Here the structure of the task (spatial navigation, transitive inference etc) is learned and abstracted in order to be reused when entering new environments. Animals (and hippocampus) do more than just space and memory. They display complex behaviours that are reused and arbitrarily combined in novel situations. This raises the exciting possibility that animals learn the structure of behaviours and generalise them to new situations (e.g. the steps to baking a cake are reusable for making cookies). The common role of generalisation and abstraction would unify representations of behavioural (reinforcement) learning with spatial map-like learning.

My research will build detailed theories and precise computational models to find a formalism with a common language for representations of reinforcement learning and space. Though much of the reinforcement learning literature has focused on more intuitive notions of reward and value to find in neural data, my models will predict that neurons additionally represent the structure of the behavioural tasks. I will look for this neural signature in data from both old and ongoing experiments.


PhD Studentship (Basic)

Modelling the impact of increased extracellular matrix stiffness on mammary epithelial cells Mammographic density (MD) refers to the proportion of the breast occupied by radiographically dense tissue, as assessed by mammography. It has been shown that women with significantly higher MD are four times more likely to develop breast cancer than those with predominantly radio-lucent tissue. High MD is associated with increased stiffness of the stromal extracellular matrix (ECM) surrounding the breast epithelial ducts. Despite a clear mechanistic link between ECM stiffness and breast cancer risk, little is known about how mammary epithelial cells (MECs) sense and respond to the altered mechanical properties of the surrounding microenvironment.

We want to understand how MECs within the duct mechanically sense altered stiffness of their surrounding ECM by using 3D culture models combined with mathematical modelling. We will utilise 3D traction force microscopy (TFM) to measure the forces on MECs within a 3D ECM model of tuneable mechanical stiffness. We will use these observations, alongside other biological readouts, to parameterise an individual-cell based mathematical model of a 3D acinar structure. We will develop this model to provide quantitative predictions enabling mechanistic insight into the behaviour of MECs and the link between high mammographic density and increased breast cancer risk.


PhD Studentship (Basic)

Quantitative investigation of the control of mRNA degradation in Drosophila early embryogenesis and the impact of stability on developmental processes Gene expression allows organisms to convert the genetic code in their DNA into proteins which carry out specialised functions in cells. In early embryonic development, cells tailor their gene expression programme to make specific sets of proteins which allow them to transform into a particular type of cell, for example, a skin cell or a neuron. Gene expression has multiple stages including how the process begins, the tuning and travel of RNA molecules along their journey, their conversion into protein as well as the mechanisms by which the cell disposes of them. My work focuses on these degradation mechanisms. We will use large datasets and computational methods including machine learning to estimate degradation rates across different genes throughout embryonic development in the fruitfly model organism and understand the mechanisms controlling these. Our findings will be validated using cutting-edge methods for imaging mRNAs. We will then use other experimental biology techniques including CRISPR-Cas9 genome engineering to change degradation rates of individual mRNAs and examine the effects on cell fates and developmental processes. This will provide us with a greater understanding of how gene expression is controlled, which has implications for many human diseases including cancer, and applications to regenerative medicine.

Gene Expression Regulation, Developmental


Dr Alexander Gusev, Dr Laura Huckins, Prof Naomi Wray, Prof Ammar Al-Chalabi

Using genetics to stratify patients and improve prediction of clinically relevant outcomes in psychiatry and neurology This project investigates the genetic basis of psychiatric disorders and neurological diseases with three key goals.

First, to gain insight into the molecular mechanisms underlying genetic associations with these outcomes through the integration of genome-wide association study (GWAS) summary statistics with a range of newly released functional genomic annotations. These include variant-level annotations such as the effect of genetic variation on gene expression, methylation and chromosome structure within relevant tissues and cell types, as well as gene-level annotations such as expression profiles across tissues, cell types and developmental stages.

Second, functionally informed polygenic scores, such as imputed and observed gene expression risk scores, will be stratified by enriched functional genomic annotations and used for clustering patients into aetiological subtypes, which will then be characterised using sociodemographic and clinical variables.

Lastly, this study will evaluate the utility of machine learning models containing functionally informed polygenic scores and cluster membership information for prediction of diagnosis, prognosis and treatment response. I will use data from a range of ancestral populations to improve the accuracy of genetic predictors in all populations. Together this project can inform novel drug development, identify clinical subgroups, and promote personalised medicine through improved prediction of clinically relevant outcomes.


Dr Tony Ly, Prof Aaron Straight, Prof Adele Marston

The role of the kinetochore in meiotic aneuploidy The kinetochore is a molecular structure that segregates chromosomes by connecting them to spindle microtubules. In the first meiotic division the kinetochores of duplicated sister-chromatids mono-orient to the same spindle pole, allowing the segregation of the paternal and maternal chromosomes. In human oocytes, meiotic chromosome segregation is highly error-prone, often resulting in chromosomal abnormalities. This worsens with advanced age, leading to miscarriages or trisomies such as Down syndrome, especially in older women. My project aims to define the molecular adaptations to kinetochores that allow mono-orientation in meiosis and understand how these might be defective in human oocytes. I will develop Xenopus laevis oocyte cytoplasmic extracts as a system in which to assemble meiotic kinetochores in vitro and use biochemical analysis to determine their molecular components. Using cell biological assays in oocytes, I will determine how these components work together to mono-orient meiosis-I kinetochores. Furthermore, I will use patient donated surplus human oocytes obtained from IVF clinics to investigate how deficiency in mono-orientation contributes to age-related chromosomal abnormalities.


Dr Adam Packer, Dr Armin Lak, Prof Kenji Doya

The role of claustrum in value-based decision-making Human and animals make decisions to harvest the most valuable rewards. This process requires a precise valuation of choice options and appropriate action selection. Despite the fact that many brain regions have been implicated in different aspects of value computation and decision making, the roles of the claustrum, a region with extensive brain-wide connectivity, in value-based decisions have remained unknown. This fellowship combines circuit, behavioural and computational tools to determine the role of the claustrum in value-based decisions.
I will train mice on a value-based decision-making paradigm. First, I will assess the importance of claustral neural activity in choice behaviour by combining viral injection strategies and three-photon microscopy. Then, I will create a biologically realistic spiking neural network and simulate the effect of claustrum on multiple upstream regions. By using Neuropixels systems and optogenetics, I will delineate how long-range inputs from the claustrum contribute to the value signal in frontal regions by recording spiking activity while silencing claustral cells. These results will provide fundamental insights into the neural circuitry of decision-making.


PhD Studentship (Basic)

“Investigating regulatory landscapes in oesophageal adenocarcinoma” Oesophageal cancer is the 14th most prevalent cancer and the 7th most common cause of cancer death in the UK.  Oesophageal Adenocarcinoma (OAC) is the most common subtype within Western populations. A poor understanding of the disease drives poor patient outcomes.

The disease is thought to arise from a pre-cancerous state known as Barrett’s Oesophagus (BO). Changes in the regulation of transcription and chromatin environment have been identified in the transition from regular oesophageal tissue to BO to OAC. This includes evidence of reversion to an embryonic developmental cell state. Additionally, Little is known about the changes in gene regulatory networks and chromatin environment which initiates and maintains metastatic cancer state.

I will use functional genomics approaches to identify elements which play a role in transcriptional regulation such as enhancers, super-enhancers and silencers. This will include developing bioinformatics methods to scale up existing unsupervised clustering methods and experimentally validating bioinformatics results e.g. endogenous reporter assays for enhancers. I will compare the regulatory landscape in regular and metastatic OAC, and embryonic tissue from the oesophagus, stomach and duodenum. This will help elucidate the origins of OAC and molecular drivers of OAC metastasis and provide bioinformatics tools potentially applicable to other diseases.


Prof Wolf Reik, Prof Bradley Bernstein, Prof Brian Huntly

Deciphering the mechanisms of epigenetic evolution driving leukaemia Epigenetic lesions occur at the early stages of cancer development, and have important roles in tumour initiation and progression. However, our understanding of how cancer cells acquire, propagate and select such aberrant epigenetic states remains very limited.

Therefore, I propose to define the mechanisms by which initiating epigenetic defects drive tumour evolution in Acute Myeloid Leukemia (AML), a deadly bone marrow cancer with no effective treatment.

I hypothesize that initiating genetic defects in the DNA methylation machinery (TET2 mutations) catalyse epigenetic diversity. The resulting epiclones might acquire properties that increase cellular fitness, predisposing cells to undergo transformation and generating a substrate for selection. Using state-of-the-art single cell DNA methylation and transcriptomic technologies coupled with lineage tracing, I will quantify stably propagated epigenetic diversity in TET2 deficient cells (Aim1), and identify selective advantage of high-fitness epiclones upon cell-extrinsic pressures (Aim2). I will then characterize putative driver epimutations in longitudinal AML patient samples and demonstrate their functional role promoting leukaemic transformation using locus-specific epigenomic editing tools (dCas9-DNMT3A; Aim3).

This research will shed light into the fundamental molecular mechanisms driving epigenetic diversification and selection of cancer cells, with the potential to bring an entirely new dimension to cancer treatment by intercepting tumour evolution.


Prof Boris Bernhardt, Prof Heidi Johansen-Berg, Prof Saad Jbabdi

How does structural anatomy enable uniquely human brain function? This project aims to advance our understanding of how the human brain evolved to support our unique cognitive skills. Using multimodal neuroimaging, I will investigate the structure-function coupling in the human brain and relate it to species differences in brain organization across the primate lineage. I will focus on the temporal lobe as a model system given its vital role in higher cognitive functions and because it underwent strong reorganization during evolution. To characterize individual patterns of brain organization optimally, I will use a gradient-based approach, where manifold identification techniques are employed to model spatial trends of variance in the data. MRI-based gradient analyses will be complemented and validated by using microstructural information from the BigBrain-Project and from gene expression data. Lastly, I will compare human temporal lobe organization to that of non-human primates to assess how divergent principles of brain organization relate to uniquely human brain function.

In sum, the present project will explore temporal lobe architecture by (1) studying human macro- and microstructural brain architecture in a gradient-based approach (2) relating structural and functional features in a unified framework to account for patterns of organization at the individual subject-level (3) comparing these relationships to those in non-human primates.


Prof Marek Basler, Prof Michael Brockhurst

The evolution of bacterial resistance to the Type 6 Secretion System Commensal microorganisms protect their hosts from pathogens, denying space and resources to would-be invaders. To bypass this host protection, many human pathogens deploy a needle-like apparatus—the Type 6 Secretion System (T6SS)—to inject lethal toxins into commensal cells, thereby establishing infection. Bacterial resistance to T6SS attacks is therefore expected to be a crucial predictor of pathogen proliferation and consequent disease severity. However, it remains unknown when, and how, bacteria evolve the capacity to resist T6SS attacks, hampering efforts to predict or leverage this host protection.

My project will address this knowledge gap by characterising the emergence of T6SS resistance in Escherichia coli. Combining in vitro and in silico approaches, I will first determine the specificity, fitness costs, and genetic bases of evolved resistance, against diverse toxins deployed by Acinetobacter baylyi, a well-studied T6SS attacker species. Next, I will examine how the evolution of T6SS resistance is affected by attacker toxin arsenal and attacker counter-adaptation, to explain why attackers typically deploy multiple toxins in nature. My ultimate goal is to provide a systematic understanding of how commensal bacteria resist toxin-mediated attacks. In the longer term, this may offer applications for the design of invasion-resistant bacterial communities, and improved biotherapeutics.

Grants awarded from 1 October 2005 to 30 June 2021


Dr Michelle Linterman, Prof Matteo Iannacone

Determining fate: Dissecting the dynamics of atypical memory B cell recruitment to protective immune responses in respiratory infection Memory B cells (MBCs) are central to co-ordinated immune responses required to resolve viral infections and mediate protection following pathogen clearance or vaccination. I propose that a newly described subset of atypical MBCs (defined by expression of CD11c and T-bet) preferentially reside within peripheral tissues, where they can differentiate in-situ to provide rapid and localised protection against pathogenic threats. This project will investigate the mechanistic basis for CD11c+T-bet+MBC differentiation following immunisation, testing the hypothesis that Th1 skewed T follicular helper cells (Tfh) regulate the divergence of CD11c+T-bet+MBCs from classical memory responses and their migration to non-lymphoid tissues. CD11c+T-bet+MBC induction will be characterised alongside subsets of Tfh subsets in vaccinated humans and mice, with fate-mapping systems and interventional mouse models used to dissect: (1) the tissue homing capacity of CD11c+T-bet+MBCs; (2) their contribution to establishing protective immunity; and (3) the involvement of CD4-derived signals to CD11c+T-bet+MBC differentiation. These will be complemented by state-of-the-art imaging technologies to visualise the spatial dynamics of CD11c+T-bet+MBCs and Tfh within germinal centre responses following immunisation. Together, these data will reveal whether Th1 polarised Tfh seed populations of CD11c+T-bet+MBCs in tissues to establish local protection against infection. Findings may facilitate tailored development of strategies to enhance immunity.


Research Development Award in H&SS

Incompleteness and the ethics of new and emerging health technologies: fostering African conversations on relational ontology, epistemic justice and academic activism In this project, we propose to create opportunities for African theory-building by fostering critical reflection, exchange of knowledge and perspectives, and collaboration and writing between African scholars from different disciplines, with a focus on exploring how African thought could influence critical engagement with the ethics of new and emerging health technologies globally. Starting with a recognition of incompleteness and the conviviality that requires, the focus of this project will be on a) developing conceptual accounts of how African thought could inform on key ethical questions raised by new and emerging health technologies, b) better understanding how we can ensure epistemic justice in our scholarship and which diversity matters; and c) understanding how particular African research contexts drive us towards academic activism. The programme seeks to create opportunities for exchange and joint reflection, in an aim to push the audacity with which African scholars can take ownership of, and lead, reflection on the ethics of new and emerging health technologies. The programme will dive into questions relating to African personhood, relational autonomy, epistemic justice and academic activism to explore how African ways of seeing and being in the world could enrich global conversations about science and technology.


Discretionary Award - Diversity and Inclusion

Lancet Commission on Gender and Global Health We are launching a Lancet Commission on Gender and Global Health that intends to ensure that global health take gender into consideration. A continued failure to consider and act on gender in public health policies, programmes and practices results in lost opportunities to improve health outcomes across society, equitably and sustainably.
We have drawn together a cross- and inter-disciplinary Commission that benefits from the expertise and experience of around 20 Commissioners from different backgrounds, geographical settings and genders. The Commission will be guided by Dr Richard Horton and Dr Jocalyn Clark from The Lancet, and will be co-Chaired by Professor Pascale Allotey from UNU-IIGH, Professor Sarah Hawkes from UCL and Mr Elhadj As Sy, Chair of the Board of the Kofi Annan Foundation.

We plan to launch the Commission in October 2020 after the Berlin World Health Summit (WHS). We will organise a 2-day meeting bringing Commissioners together for the first time, to discuss the direction and content of the Commission and establish a workplan covering the next 2-3 years. Funding is required to host the launch in Berlin, and to follow up with post-launch co-ordination and communication activities.


Prof Shaul Druckmann, Prof Rachel Wilson, Prof Scott Waddell

Sir Henry Wellcome Postdoctoral Fellowship

A neural Cartesian coordinate system for generating flexible internal goals The Drosophila brain provides a unique opportunity to study the neural mechanisms underlying navigation. Recent work has revealed much about the fly brain’s ring-shaped ‘compass’ region. Within it, a single ‘compass needle’ of activity represents the fly’s heading. When the fly is pursuing a specific heading goal, it locomotes in a straight line, often holding the sun at a specific arbitrary angle (e.g., 90°), which holds the 'needle' stationary. If the fly is pushed off course, the circuitry downstream of the compass kicks in to reorient the fly toward its goal, moving the sun back to 90° and the ‘needle’ back to its original state. How does the brain initialise a specific angular goal (e.g., holding the sun at 90°)? We hypothesise that an asymmetry in a specific brain region (called the asymmetrical body) provides a coordinate system for writing new spatial goals into working memory. This asymmetry may be used to initialise a new spatial goal with respect to a landmark at an arbitrary angle. I will i) use computational modelling to explore the predictions of this hypothesis, ii) use calcium imaging to test these predictions, and iii) use specific genetic manipulations to perturb this process.


Multiscale computational and experimental investigation of ventricular arrhythmogenesis in diabetes Ventricular arrhythmia is the leading cause of death in diabetes, but its mechanisms remain poorly understood, leading to suboptimal therapy. I propose an interdisciplinary project to address this unmet need, combining multiscale human cardiac simulations and experimental studies. I will use my recent computational model of a human myocyte ToR-ORd, which was extensively validated for arrhythmia research, disease representation, and drug assessment.

Goal 1) To build a computational model of a single diabetic myocyte and use it to elucidate how distinct aspects of diabetic remodelling contribute to arrhythmia, also investigating the role of glucose level disturbance.

Goal 2) To demonstrate how remodelling of cardiac sympathetic signalling at the myocyte level affects diabetic arrhythmia vulnerability using simulations informed by newly collected FRET imaging data.

Goal 3) To integrate the single-cell results into 3D models of ventricles based on patient-specific clinical imaging data, investigating the diabetic remodelling of cardiac conduction properties.

Goal 4) To produce a computational tool to search for new drugs with promising antiarrhythmic effects in diabetes and to assess existing therapies, suggesting their optimisation.

In summary, the project is likely to impact future diabetic therapy and to bring new insights into the so-far poorly understood area of diabetic arrhythmogenesis.


PhD Studentship (Basic)

Investigation of the structural and biochemical properties of mammalian tolloid proteinases The family of BMP1/Tolloid-like proteases (B/TPs) is involved in a variety of important functions in mammalian tissue development. Firstly, B/TPs cut collagen precursors to allow their assembly in the extra-cellular matrix (ECM). Mutations or a loss of function of B/TPs result in several developmental defects or can result in death during the embryonic stage. The second role of B/TPs is activating different growth factors. These messenger molecules are involved in communicating with cells during the formation of different tissues, including bones and the brain.

Our work aims to understand how B/TPs carry out their function and how mutations result in diseases. To do so, we aim to determine the 3-dimensional structure of two members of the B/TP family using cryogenic electron microscopy. Furthermore, we want to understand how B/TPs interact with their substrates, as well as known effector proteins. We hope our results will allow for a better understanding of B/TP function and regulation and provide potential basis for therapeutic approaches for B/TP-associated diseases.


Dr Leo Carlin, Dr Roser Vento-Tormo, Dr Megan MacLeod, Prof Gerard Graham

NK cells in memory responses to influenza: Which, Where and How? NK cells are innate lymphocytes with crucial roles against viruses and tumours. There is growing evidence that NK cells display immune memory, however many key open questions remain. While memory NK cells where shown in several models and proved to be protective in adoptive transfer experiments, the mechanisms behind these phenomena remain unclear. Answering such questions could reshape our understanding of immune memory and provide new strategies against infectious disease and cancer. Using state-of-the-art scRNA-seq, 3D imaging and precision mouse models, I plan to study NK cell memory following influenza infection. I aim to decipher 1) which subpopulations of NK cells acquire memory, 2) where memory NK cells are located within the lung architecture and which cells (adaptive, innate or stromal) they interacting with, and 3) how memory NK cells act in concert with other memory cells in secondary immunity in immunosufficient hosts. With my background in NK cells and innate memory and the excellent array of sponsors with complementary expertise in influenza, chemokines, computational analysis and 3D imaging, this project provides the ideal platform for novel findings in the field of NK cell memory, expansion of my skillset in cutting-edge techniques, and optimally enables my transition to independence.


PhD Studentship (Basic)

Structural and Biophysical Characterisation of ESCRT-0 In order to sense and respond to outside events, eukaryotic cells utilise many different proteins on their surface to finely control activities such as growth and movement. Key to regulating these processes is the uptake of these proteins from the cell surface, and their destruction at the lysosome in a process coordinated by the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery. The first of these complexes, ESCRT-0, recognises a universal signal (ubiquitin), which is attached to these proteins and marks them for destruction by directing them to the lysosome where they are broken apart and recycled. In order to understand how ESCRT-0 works, we need to know what it looks like. We intend to investigate this by using the technique cryo-electron microscopy, which will allow us to understand the shape of ESCRT-0 at the atomic level. We will also use an array of biophysical techniques to investigate how the structure of ESCRT-0 changes when it binds to ubiquitinated proteins, and whether this binding helps to promote the subsequent stages of the ESCRT process. Together, this should tell us what the role of ESCRT-0 is at the head of the ESCRT pathway.


Dr Leigh Johnson, Dr Andrea Low, Prof Peter Vickerman, Prof Thorsten Wagener

Investigating the effect of climate extremes and global warming on HIV outcomes in sub-Saharan Africa Sub-Saharan Africa (SSA) has the highest HIV burden in the world and will be the region most affected by climate change, with the largest projected decrease in rainfall and limited resources to deal with the consequences. Global warming will lead to more droughts and decreased food yields, resulting in increased food insecurity. Emerging evidence suggests food insecurity could lead to increased HIV transmission risk and sub-optimal HIV treatment outcomes, due to such factors as women resorting to selling sex for survival, access to HIV treatment being interrupted, and decreased HIV treatment absorption in the absence of food.

This project will:

- involve epidemiological analyses (regression, systematic reviews, meta-analyses) on large HIV datasets from SSA to improve the evidence base for the effect of drought and food insecurity on HIV treatment outcomes, HIV incidence and sexual risk behaviours in SSA.

- use mathematical modelling to simulate the existing impact of drought and food insecurity on HIV transmission and morbidity in several countries in Eastern and Southern Africa.

- model the potential effect of global warming in these countries on increasing the impact of drought and food insecurity on HIV transmission and morbidity, as well as the impact of potential interventions.


Anomalous Transport of Organelles

PhD Studentship (Basic)

Anomalous Transport of Organelles From active transport by motor proteins to passive transport in the crowded cytoplasmic environment, the movement of organelles within cells is critical for cell function. This transport exhibits non-Brownian anomalous transport: sub-diffusion and super-diffusion. Abnormal transport can lead to disease, and understanding how this occurs requires systematic quantification of organelle movement combined with predictions based on biologically motivated random walk models with multiple states of motion. To simplify tracking and analysis we will study organelle motility in neurons that are one dimensional, due to the thinness of the axon, rather than the fibroblasts we studied previously. We will obtain and analyse organelle trajectories by live-cell imaging of cultured human neuronal-like cells, and individual neurons in the nematode C. elegans. Then we will determine how selected disease-causing mutations in dynein regulators affect motility. We will develop new mathematical models for non-Markovian stochastic transport and fractional Brownian motion with random Hurst exponents, validating and improving models using experimental data. Lastly, we will generate new neural network/machine learning algorithms to better segment and estimate different states of motion and use these to predict the effect of dynein disruption on motility in human motor neurons that can be 1m long.


Dr Arnau Sebé-Pedrós, Prof Robert Klose, Prof David Booth

Unravelling the mechanisms of mammalian Polycomb-dependent gene repression through functional evolutionary analysis Polycomb group proteins are chromatin regulators which are essential for mammalian development and are often dysregulated in diseases including cancer. Polycomb proteins make up two distinct complexes, Polycomb Repressive Complex 1 and 2 (PRC1/2). In mammals these complexes have expanded and evolved into a complex interconnected system making it challenging to disentangle the core principles through which they function. I will utilize Salpingoeca rosetta, a choanoflagellate, to dissect a more "ancestral-like" Polycomb system and through a comparative approach unravel the basic core principles through which animal PRCs operate. Firstly, I will interrogate the composition (Aim1) and dissect the biochemical properties and enzymatic activities of S. rosetta (Sr)PRCs (Aim2) to reveal the conserved properties of animals PRCs. I will then utilize genome-wide mapping approaches to address the function of SrPRCs and, using mutants for PRC components, test whether their activities are coupled in the genome (Aim3). Together, these discoveries will provide essential new insight into the principles through which animal PRCs act and will shed light on how they become perturbed in disease. This in turn will inform new avenues for targeted therapeutic intervention in diseases where alternations to PRC function are pathogenic.


PhD Studentship (Basic)

Characterising the Novel Role of Inositol-5 Phosphatase B in B Cell Receptor Activation, Endocytosis and Signalling White blood cells (WBCs) play a fundamental role in coordinating our immune system in response to infection. WBCs known as B cells produce antibodies and contribute to lasting immunity upon re-exposure to the same infection. Unfortunately, B cells are also responsible for various immune disorders and lymphatic cancers. This makes understanding the mechanisms controlling B cell behaviour vital for treating these diseases. B cell physiology is heavily regulated by a cell surface receptor known as the B cell receptor (BCR). We have uncovered a novel mechanism by  BCR function is mediated through a specific enzyme that targets fat-like molecules called lipids. I aim to understand this previously unappreciated mechanism of regulation using a multidisciplinary approach. I will use biochemical and mass spectrometric approaches to determine how these enzymes are recruited to BCRs. I will genetically engineer cell lines which lack these enzymes to explore the functional impacts of their absence on BCR activation and signalling, measuring changes using flow cytometry and cutting-edge live-cell microscopy. Validating these enzymes as critical for BCR function will not only enhance our overall understanding of this complex process but also reveal new targets for therapeutic intervention.


Prof Andrea Danese, Dr Charlotte Cecil, Prof Jaakko Kaprio, Prof Mark Gilthorpe, Dr Jean-Baptiste Pingault, Prof Marcus Munafo

Testing the role of physical activity in promoting resilience against stress-related psychopathology among young people
Stress-related psychopathology (e.g. depression and anxiety) affects one in eight children in the UK. It is therefore crucial to identify modifiable protective factors that can promote mental health in young people. Physical activity is a promising target for the prevention of depression and anxiety. However, the extent to which it can reduce the burden of mental disorders in young people is not known. This is due to the breadth of environmental, social, and genetic factors that could confound the relationship between physical activity and psychopathology. Furthermore, it is unclear whether physical activity can promote resilience to psychopathology in children who are at higher risk by virtue of genetic liability or adversity.

I will apply cutting-edge causal inference methods, such as G-methods, Mendelian randomisation, and twin designs, to test whether physical activity can promote resilience against the development of stress-related psychopathology, using data from large population-based cohorts of children from the UK, Netherlands, Norway, and Finland. Triangulating evidence from multiple analytical approaches will allow me to strengthen causal inferences from observational data and minimise potential biases associated with each method. In turn, the findings will indicate whether interventions targeting physical activity are likely to hold promise to prevent stress-related psychopathology.


PhD Studentship (Basic)

Molecular and cellular mechanisms directing neuronal microtubule rearrangements during vertebrate CNS development Polarity, the asymmetric organisation of cellular components, is crucial for the function of many cell types. Newborn neurons in the developing spinal cord shed their tips to move to their final location, causing them to lose polarity and the ability to distinguish their front from their back. These neurons must then regain polarity to extend a long process, called an axon, which makes connections with other neurons. In the developing embryo, neurons polarise in response to external cues from the surrounding tissue, which determine the orientation in which the axon will form, and therefore the direction it will grow in, or if it forms at all. Thus, neuron polarisation is essential for the formation of neuronal circuitry; however, the mechanisms of vertebrate neuron polarisation within tissue are unclear. I will study the molecular and cellular mechanisms that direct this key cell-biological process using cutting-edge live imaging and super-resolution microscopy of developing neurons in the embryonic chick spinal cord. Not only will this work help us understand how the nervous system is built, but it will also enrich our understanding of the general cellular mechanisms of polarity transition in development and disease.


Prof Antonio Vidal-Puig, Prof Kathryn Lilley

Unravelling the molecular signalling underlying human brown adipogenesis Obesity and associated comorbidities are significant unresolved global health problems. Despite intense research and various social policies, most of the available non-invasive treatments are ineffective in the long term, and the best therapeutic option remains highly mutilating bariatric surgery. Thus, the unmet need is to identify novel, long-term safe treatments. The activation of the brown adipose tissue (BAT), an energy-dissipating organ, is a promising strategy to treat obesity if the challenges of accumulating enough BAT mass and optimised activity are resolved. Since obese people do not have enough BAT, it is crucial to identify at which step of the differentiation and/or activation the BAT of obese patients fails, and whether we can pharmacologically bypass these functional bottlenecks. Recently, Vidal-Puig's lab has optimised a unique differentiation protocol that recapitulates step-by-step the developmental path of human BAT from stem cells. I aim to use this tool to decipher the signals regulating the process and provide an accurate stage-by-stage molecular map of human brown adipogenesis. These data will help to infer novel pharmacologically targetable molecules to improve differentiation and activation of BAT in obese patients and provide essential information for its analysis and classification in patients based on its maturation and functional stage.

Grants awarded from 1 October 2005 to 30 June 2021


Prof Adolfo Bronstein, Prof Stephen Lord

Identifying the Neural and Cognitive Contributors to Dizziness in Older Adults Dizziness is common in older adults and is strongly associated with more frequent falls. Nonetheless, treating this condition represents a significant challenge as clinicians are often unable to identify a physical cause (and, thus, dizziness is ‘unexplained’). Pilot work implies that unexplained dizziness may stem from attempts to consciously process balance. However, a causal relationship has not been established. Further, the specific mechanisms through which conscious processing influences dizziness remain unknown. My goals are to (i) investigate whether conscious balance processing is causally associated with symptoms of unexplained dizziness, and (ii) identify the neuro-cognitive mechanism/s that likely underpin such a relationship.

I will conduct a programme of research to test the hypothesis that conscious balance processing influences dizziness through a hypersensitivity to sensory input, in that even minor fluctuations within ‘normal’ bounds are perceived as unsteadiness. I will measure symptoms of dizziness and assess sensory processing during baseline balance conditions, as well as during experimental manipulations that either promote or prevent conscious balance processing. Data will be compared between older adults with unexplained dizziness and age-matched controls. This work will advance our understanding of how neuro-cognitive factors contribute to dizziness, informing the development of novel therapies that target these mechanisms.


Discretionary Award - Mental Health

The State of the World's Children 2021 Focus Groups UNICEF proposes multi-country focus groups to gather insights on young people’s mental health and well-being. This reflects our and Wellcome Trust’s mutual commitment to engaging youth as partners in the design and implementation of action research that affects them. The proposed research will be featured in UNICEF’s flagship State of the World’s Children report, ensuring that the knowledge, expertise, and lived experiences of young people are part of the global dialogue on research, policy, and programming priorities.

Key research questions include:

 How do adolescents perceive and understand mental health, both positive and negative?
 What are the key emotional and behavioral challenges facing adolescents in communities around the world, and what do they identify as risk and protective factors?
 What are the positive and harmful ways adolescent are coping with mental health problems?
 What are the barriers and reinforcing factors to their help-seeking behavior?
 What are adolescent ideas and solutions around structural, community, peer, and self-care approaches to mental health promotion, prevention, and support?

This research will create opportunities both for promoting positive youth development as well as increase youth voice in the scientific study and body of evidence around mental health of young people.