PhD Training Fellowship for Clinicians

The implementation of atrial fibrillation screening in primary care: a mixed-methods process evaluation of the SAFER trial In atrial fibrillation (AF), the heart beats irregularly. This may produce no symptoms but can cause stroke: 1 in 10 strokes occur in people who do not know that they have AF. Subsequently, there are calls for screening for AF but we first need information on whether screening reduces strokes and is cost-effective. The SAFER trial will study this by comparing the rates of stroke (and other conditions) in general practices that screen to those that do not.  Some practices will be given training to perform screening but how they implement it will affect whether screening improves health.

I will review evidence for how practices can best implement screening. I will observe how practices implement AF screening by examining training, day-to-day running, consultations, communications, and interviewing staff. I will send quarterly surveys to practices that perform and do not perform screening to see how they differ. I will finally combine my research to discover how best to implement AF screening.

My results will guide practitioners and researchers on screening. It will help the trial run AF screening more successfully and explain the trial results more clearly. We can then recommend to screening agencies how AF screening programmes should be run.


PhD Training Fellowship for Clinicians

Genetic approaches to gain new insights into cellular iron metabolism and oxygen sensing Maintaining appropriate levels of iron in the body is indispensable for human survival. Low iron levels can lead to anaemia and are an important feature of cancer. Too much iron can result in the death of cells and contribute to chronic diseases affecting the lungs, liver and brain. Therefore, most organisms have developed mechanisms to adapt to the abundance of iron in their environment, but our understanding of how iron is regulated within cells remains poorly understood.

Here, I propose to use forward genetic approaches in human cells to uncover new pathways for iron regulation. We have developed a dynamic iron fluorescent reporter, based on the sensitivity of Iron Regulatory Protein 2 (IRP-2) to iron availability, and will use this reporter in genome wide mutagenesis screens to find genes that are required to regulate iron. Ultimately this work will identify new elements of the iron pathway and potentially uncover novel targets for drugs to treat a range of diseases which are worsened by dysregulation of iron levels.

Grants awarded from 1 October 2005 to 30 June 2021

Creative Commons Attribution 4.0 International (CC BY 4.0)


PhD Training Fellowship for Clinicians

Investigating the ageing phenotype in the bone marrow microenvironment: the role of macrophages in regulating normal and malignant haematopoiesis  Most people diagnosed with Acute Myeloid Leukaemia (AML) die of the disease because the available chemotherapy targeting AML cells cannot kill all the leukaemia cells in the bone marrow. In part, this is because the bone marrow environment promotes leukaemia growth and also provides protection from the drug treatment. It is hoped that future treatment strategies targeting the environment and the tumour (the soil and the seed) will lead to improved outcomes for patients. This project aims to understand the cancer-specific protective functions of the bone marrow with a view to identify new treatments in the future.

We have recently discovered that AML cells cause senescence, the process of ageing of cells in which cells permanently stop dividing, in the bone marrow and that this supports the survival and growth of leukaemic cells. Senescence normally occurs with ageing and the fact that AML occurs most commonly in older people is consistent with the observation that the leukaemia thrives on converting the bone marrow microenvironment into a senescent environment. During this fellowship I plan to further investigate the impact ageing has on the bone marrow microenvironment and how this in turn impacts on tumour development.


Creative Health Centre for the UK

Discretionary Award – C&S

Creative Health Centre for the UK Contribution to the establishment of a national Centre for Creative Health as recommended by the APPG report into Creative Health: Arts , Health and Wellbeing (2017).


PhD Training Fellowship for Clinicians

Defining the pathophysiology of snakebite induced local tissue damage and evaluating tolerance of a repurposed orally administered venom inhibitor Snakebite is a priority neglected tropical disease and has been under-researched, particularly in sub-Saharan Africa.

The numbers who suffer snakebite are often under-appreciated, as many victims do not attend hospital. We will survey people in the community to identify the number of bites per year in Kilifi, Kenya. At Kilifi County Hopsital, relatively detailed information about snakebite cases has been collected, and this will be analysed to identify the burden of disease. All new cases of snakebite presenting to Kilifi County Hospital will be invited to enrol in an observational study. This observational study will aim to uncover the important biting species of snake, the rates of skin damage and to explore the underlying causes of skin damage.

Many snake venoms contain "SVMP" toxins. These need zinc in order to function. SVMPs can damage blood vessels and interfere with normal blood clotting, and this can lead to bleeding. Unithiol has been used to treat heavy metal poisoning, but recently it has been shown to prevent death in mice following snakebite. We plan to give this drug to healthy volunteers in Kenya, in order to understand its safety, and to decide what dose is best to give in future research studies.


PhD Training Fellowship for Clinicians

The effect of lipid-lowering agents and the dysregulated metabolism on the risk and progression of head and neck squamous cell carcinoma (HNSCC). Background

Drugs such as statins reduce blood cholesterol, but they may also lower the risk of getting certain cancers, however the evidence surrounding head and neck cancer is inconclusive. In addition, the mechanisms by which these drugs might prevent head and neck cancer requires further evaluation.

Statins and similar drugs modify circulating blood factors such as cholesterol, hormones and metabolites which result in the exposure of cells to an environment that may alter the chances of a cancer developing. We want to determine whether such changes to the body’s metabolic environment also influences the likelihood of developing and dying from head and neck cancer.

Research approach

1) Analyse large datasets of people with head and neck cancer, to determine if statins and similar drugs causally protect against cancer development and progression.

2) Explore how changes in cholesterol, hormones and metabolite levels might mechanistically prevent head and neck cancer using laboratory studies.

3) Identify potential drug targets for prevention or therapy in head and neck cancer.

Impact

This project will investigate the link between changes to the body’s cholesterol, hormones and metabolite levels and head and neck cancer. This could help inform targeted cancer screening, prevention and intervention for these patients.


Our Health Matters

Discretionary Award - Public Engagement

Our Health Matters This 12-month pilot project would test how we can use our innovative journalistic approach to find more effective, scalable ways to engage diverse audiences around health issues and research. The opportunity for collaboration with Wellcome will bring together our expertise in local engagement and community-led investigations across the UK with our global health track record of fact-based reporting and expert, external networks. A new Bureau Local health team will explore and test issues that impact nationally and globally with local communities to find connections.

If successful, an immediate outcome would be that we’d improved relevance and relatability around a critical health topic (and research around it) for affected communities and the wider public across the UK. For the longer term, our project would strengthen understanding of how engaged journalism can support a two-way flow of communication from and to affected communities. We would hope the findings from this project could support a collaborative framework for journalists, communities and researchers to use local investigative journalism to connect and engage people more effectively with health issues.


PhD Training Fellowship for Clinicians

Exploiting Radiogenomics for Evaluating Intratumoural Heterogeneity and Therapy Response in Soft Tissue Sarcoma Soft tissue sarcomas (STS) are a rare group of cancers that can develop throughout the body. There are over 100 subtypes, which often exhibit different tissue compositions across a single tumour. STS tumours therefore behave variably to treatment, and predicting patient response to pre-operative therapy is challenging. Advancements in MRI provide insight into the behaviour of tumours without needing an invasive biopsy. However, we lack research comparing MRI with tumour tissue to allow confidence in MRI interpretation. This project seeks to gain a better understanding of the differences seen in STS, and establish if imaging can reflect the underlying biology of these differences.

I aim to match image-guided sampling of multiple regions of STS tumours with molecular analysis. The analysis will investigate the DNA, RNA and proteins within the tumour tissues and how this relates to MRI. We will assess whether integrating molecular and imaging data can improve our understanding of whether tumours are responding to treatment.

My research will increase our understanding of the complex nature of STS and why distinct tumour regions behave differently. This will impact clinical practice by enhancing our ability to accurately measure and predict responses to pre-operative therapy and facilitate delivery of precision medicine.


Electrifying Life Science

Strategic Support: Science

Dr Mark Basham, Prof David Stuart, Dr Christopher Russo, Dr Gwyndaf Evans, Dr Richard Henderson

Electrifying Life Science The ability to image life lies at the heart of biology and medicine. Imaging the molecules of life leads directly to discoveries since they can then be understood in atomic detail. For molecular imaging, electrons give more signal for less damage than X-rays, as demonstrated by the current success of single-particle electron cryomicroscopy. The key recent breakthrough underpinning this technology was the development of direct electron detectors for cryoEM, based on silicon computer chip technology from the 1990s. The promise of using electrons in structural biology more broadly is still held back by several technological hurdles. Here we propose a major cross disciplinary effort to develop new technologies that use electrons to revolutionise biology. There are three components: AMPLUS – using electrons to visualise proteins inside cells, (electron cryotomography) at unprecedented resolution, cryoEM100 – a ten-fold cheaper purpose-built cryomicroscope that will democratise single particle imaging, and HEXI – a project that will create a world-leading combined X-ray and electron beamline, enabling structure determination from crystals ranging from the smallest that exhibit Bragg diffraction up to those useable at a microfocus X-ray beamline.


Electrifying Life Science

Strategic Support: Science


PhD Training Fellowship for Clinicians

Analysis of the interplay between replication stress and immune responses in SMARCA4 and ARID1A mutant cells Cancer cells are growing and dividing very rapidly. Rapid division is stressful, and can result in signals being sent to the immune system. In this case, therapies that help the immune system (immunotherapy) to attack the cancer cells are very useful. The SWI/SNF complex is a set of proteins in the cell that help to protect the DNA from stress caused by rapid division. This complex is frequently lost in cancer cells. Here, I will investigate whether by helping cells deal with the stress of dividing, the SWI/SNF complex prevents the immune system from turning on. By understanding this, we can have a better idea about which cancers will respond best to immunotherapy, and what other therapies might work well in combination with immunotherapy for these cancers.


Publishing WHO R&D Roadmaps

Discretionary Award - Vaccines

Publishing WHO R&D Roadmaps

Background Information:

The research and development (R & D) Blueprint is a global strategy and preparedness plan to address highly infectious diseases and strengthen the emergency response by bringing medical technologies to patients during epidemics. For each of these priority diseases, WHO is coordinating the elaboration of R & D roadmaps, to serve as collaborative frameworks underpinning strategic goals and research priority areas to accelerate the development of diagnostics, therapeutics and vaccines to prevent and control severe emerging diseases. R & D roadmaps have been developed for 4 priority diseases with epidemic potential: Crimean-Congo hemorrhagic fever and Ebola/Marburg virus diseases, Lassa Fever and Nipah virus disease.

Key Goals:

Effective publication and dissemination of these roadmaps, together with communication and advocacy, will help to achieve the R & D blueprint and roadmaps goals.

How the funds will be used:

To support the publishing costs of 4 of the Research and Development (R & D) Blueprint Roadmaps.


Discretionary Award - REiAA

International Research Management Staff Development Programme This project is based on an invitation by the African Academy of Sciences (AAS) to the Association of Research Managers and Administrators (ARMA) in the UK, to contribute to their ongoing ReMPro programme. Drawing on their expertise and strengths as an association of research managers and administrators, ARMA will support ReMPro's strand on developing individual capacity of research management staff through various activities like, needs analysis and mapping workshops and implementation of an International Research Management Staff Development programme. ARMA is seeking funding to reinforce existing support to the project, specifically towards the International Research Management Staff Development Programme and personnel costs for the second phase.

1. International Research Management Staff Development Programme -  aimed at strengthening capacity of research management staff in Africa, this will be an exchange programme between African and UK institutions. Participants will be drawn from diverse institutions through a competitive application process.

2. Personnel costs - to implement and oversee the activities, ARMA has employed a programme manager with a projected budget covering 12 months. However, their is a clear need to develop and implement outcomes from the mapping workshops. This will be carried out in the second phase of the programme.


Discretionary Award - Policy

Wellcome support for Understanding Animal Research Support for UAR activities as per uploaded document


The Cambridge History of Medicine

Discretionary Award – C&S

The Cambridge History of Medicine This application is for support to develop a proposal for The Cambridge History of Medicine in six volumes. As General Editor, I will meet with a team of a dozen volume editors at a series of workshops to ask fundamental questions about what the history of medicine is, what it should be, and how best to represent it in these books.


Discretionary Award - Snakebite

An integrative approach for improving the immunization of horses for the production of antivenoms Animal-derived antivenoms are the mainstay in the therapy of snakebite envenoming. There is an urgent need to develop knowledge-based protocols for the immunization of horses, as this key aspect of production has lacked research and innovation. This project is aimed at developing protocols for the management of horses used for immunization with venoms in a pilot farm. The following aspects will be investigated: (1) Evaluation of feeding protocols; (2) veterinary care and management aimed at minimizing the deleterious effects of venoms; (3) selection of the most appropriate adjuvants for immunization and development of new immunization schemes for generating high antibody titers; (4) design of bleeding protocols providing a high yield of plasma while not affecting the overall condition of horses. The project is also aimed at selecting the best combination of venoms from African snakes in order to generate a polyspecific antivenom of wide neutralizing coverage, as well as to device ways to improve the antibody titers against poorly immunogenic low molecular mass neurotoxins from snake venoms. In order to apply the principle of 3Rs (Replacement, Reduction and Refinement) in the assessment of antivenom potency, in vitro tests will be evaluated for their correlation with in vivo toxicity assays.


Innovator Award

Prof Jeremy Lambert, Prof Simon Ward, Dr Olivera Grubisha

Proof-of-Concept for a5-GABAAR PAMs in the treatment of psychosis’ Recent evidence suggests that a part of the brain called the hippocampus is responsible for
the increase in dopamine in a different part of the brain, the striatum, known to cause
psychosis. Our hypothesis is that by attenuating activity within the hippocampus, we will then
be able to reduce the increase in dopamine associated with psychosis. In order to do this,
we plan to target the GABA chemical signalling pathway which inhibits nerve cell excitability.
More specifically, we aim to increase the inhibitory actions of the so-called alpha5-GABAAR
protein, which is highly expressed within the hippocampus and is therefore ideally placed to
control overall hippocampal activity. In this proposal, we will identify molecules that
selectively enhance the function of GABA at alpha5-GABAARs and then test representative
compounds in an animal model of schizophrenia to see if they do indeed attenuate
increased dopamine activity.


Evidence Accelerator - Employee Health

Discretionary Award - Public Engagement

Evidence Accelerator - Employee Health Over 30m days are lost to work-related ill health annually in the UK. Of all employers’ health-related investments, only 5.6% are being used by employees and under 15% are evidence-based.

Our aim?

Develop, test, and scale an ‘Evidence Accelerator’ that bridges the gap between science, research and the workplace. Using design methods to translate evidence into action, with employers as the bridge, it’ll provide ways marginalised employees can access, use and respond to scientific health research and improve their health.

We will

 narrow in on key mission areas where under-utilised EVIDENCE shows most promise to positively impact marginalised workers’ health, (e.g. mental, musculoskeletal)

 ENGAGE cohorts of employers across industries with marginalised workers most susceptible to those health issues

 prototype and test a wide range of design-led and evidence-based workplace interventions to ACCELERATE the flow of evidence into the workplace

 explore which offer demonstrable positive impact on workers and organisations as a result of their involvement, and which show most promise of a model that can SUSTAIN

Success means:

 Marginalised workers are accessing, using, responding to health research and truly improving their health and wellbeing

 More researchers and employers engaged in informing evidence-based, design-led workplace interventions

 Sustainable operating and business model


PhD Training Fellowship for Clinicians

Determining the role of Phosphoinositide 3-kinase delta (PI3Kδ) in the pathogenesis and progression of COPD  Smoking and other inhaled toxins can cause chronic obstructive pulmonary disease (COPD). Periodic worsening of symptoms ('exacerbations') can lead to hospital admission or even death. Exacerbations are mostly driven by bacterial infections; a bug called non-typeable Haemophilus influenza (NTHi) is a common culprit. A protein called phosphoinositide 3-kinase delta (PI3K-delta) makes patients more susceptible to respiratory infections in several ways and may increase risk of COPD.

Using mice with normal or over-active PI3K-delta activity I will assess their susceptibility to developing COPD (using inhaled chemicals that cause COPD) and also NTHi infection (by infecting them with NTHi and seeing how they clear it). I will then give the mice a drug that reduces PI3K-delta activity to see if this has a protective effect on COPD development. I will interrogate samples from COPD patients for evidence of abnormal PI3K-delta activity. I will do this by 1) measuring activation of PI3K-delta in blood immune cells and 2) assessing protein levels of PI3K-delta and its downstream targets in lung tissue.

My work will offer insights into mechanisms underlying COPD development and potentially identify novel therapeutic targets for this disease. It will also shed light on whether PI3K-delta confers enhanced susceptibility to NTHi infection.


DFID-Wellcome Epidemic Preparedness Grant

Coalition for Epidemic Preparedness Innovations (CEPI)

Evaluation of a heterologous, two-dose preventive Ebola vaccine for effectiveness and safety in the Democratic Republic of the Congo  A large-scale study in the Democratic Republic of Congo (DRC) to deliver Janssen's candidate Ebola vaccine regimen VAC52150 (Ad26.ZEBOV, MVA-BN-Filo). The vaccine Ad26.ZEBOV (5x1010 viral particles[vp]) will be given as the first dose and the vaccine MVA-BN-Filo (1x108 infectious units [Inf U]) will be given as the second dose 56 (-14 day +28 day) days later, to adults, and children aged 1year or over. Evaluation of this intervention will include the estimation of the effectiveness of the two-dose vaccine regimen to prevent Ebola Virus Disease (EVD) and a qualitative component of the understanding and perceptions of individuals of this study. The primary objective is to estimate the effectiveness of vaccination of the population with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen for the prevention of EVD in adults and children aged 1 year or above. The study sponsor will be the London School of Hygiene and Tropical Medicine (LSHTM). The study PI will be Professor Jean-Jacques Muyembe-Tamfum from the DRC Institut National de Recherche Biomédicale (INRB).


Innovator Award

Miss Claire Foley, Ms Alison Deary, Mr Christopher Deane, Dr Nicola Curry, Mrs Helen Thomas

A multi-centre, prospective, double-blinded, pilot study evaluating artificial intelligence driven automatic detection of proximal deep vein thrombosis (DVT). Deep vein thrombosis (DVT) is a condition where blood clots form in the veins
of the body, most frequently the leg. It is a serious condition and if left untreated
clots can move to the lungs, which can be fatal. Early diagnosis is vital. Normally
three steps are needed for a DVT diagnosis: a GP appointment; a hospital DVT
clinic appointment and a leg ultrasound scan. This process should take only 4
hours, but it often takes longer and therefore a precautionary anticoagulant
(blood-thinning) drug is given. Nearly 90% of people investigated for a DVT have
no clot.


Innovator Award

Dr Aldo Tagliabue, Mr Riccardo Baccheschi

‘Modified Outer Membrane Vesicles as safe, effective, low cost, multivalent vaccines against typhoid and paratyphoid fever and invasive non-typhoidal Salmonella infections’ Salmonella are bacteria that cause life-threatening infections in adults and children. These diseases co-exist in many geographical areas, especially in Low and Middle Income Countries. Therefore, a vaccine that can protect against all the major Salmonella infections would be highly desirable. The project will exploit the remarkable features of Outer Membrane Vesicles (mOMV) to deliver antigens from many species of Salmonella that cause disease in humans. mOMV are outer membrane blebs naturally shed by Gram-negative bacteria, including Salmonella. These bacteria can be genetically manipulated to increase mOMV production, to decrease adverse reactions and to include additional antigens. mOMV are easy and cheap to produce, strongly immunogenic and protective. The innovator award will therefore allow the development of a multivalent, easy to produce, low-cost, safe, effective Salmonella vaccine to be taken towards the end of preclinical experimentation.


Sir Henry Wellcome Postdoctoral Fellowship

Defining stem cell states competent to self-organize morphogen signalling centres in human neural tube organoids Groups of cells called 'organizers' release signals to induce cell fates during development. Remarkably, organizers can undergo ‘self-organization’ in 3D organoids. Understanding this phenomenon has profound implications for engineering and regenerating patterned tissues with bonafide cell-type complexity and 3D-architecture.

Mouse pluripotent stem cells (PSCs) can form neural-tube (NT) organoids. Timely retanoic acid (RA) addition induces scattered precursors that self-organize into a floorplate organizer, which drives ventral-dorsal patterning. I will create cognate human (h)NT organoids from single naïve hPSCs. Exploiting advanced bioengineering technologies, I will isolate organoids from confounding inter-organoid communication and promote robust self-organisation. This interdisciplinary approach will enable me to probe previously inaccessible questions regarding complex mechanisms.

Using this system, I will study how cellular competence to express morphogens is subject to strict temporal regulation. Why is there a restricted window-of-competence for RA response, and how does this trigger self-organization? I will molecularly profile the transient competent state, functionally define the gene-regulatory basis for competence restriction, and investigate how molecular changes at this time serve as the basis for long-range self-organizing behaviour.

This will provide a 3D model for critical stages of human nervous system formation, and reveal how self-organization processes are adapted for human-specific developmental size and timing.

Grants awarded from 1 October 2005 to 30 June 2021


Spineless in the gut - intestinal function of the aryl hydrocarbon receptor from flies to mammals The aryl hydrocarbon receptor (AHR) has essential functions in the intestine, protecting mice from infection and cancer. However, the underlying mechanisms are still unclear as research has been hindered by the complex regulation and multiple feedback loops governing mammalian AHR. I will therefore use a simpler model system. Spineless, the homolog of AHR in Drosophila, binds the same DNA motif as AHR, but is regulated only on the gene expression level. My preliminary data suggest that Spineless may have similar functions to AHR, influencing epithelial regeneration and survival during infection. I will take advantage of this simpler pathway and the genetic tools and ease of manipulation in the fly in order to rapidly dissect how AHR/Spineless expression is regulated and to systematically analyse its target genes. I will first generate the necessary tools and then answer three main questions: what are the target genes of Spineless, how is Spineless gene expression regulated, and how does Spineless function in the context of intestinal infection. Results obtained from these experiments will be compared with existing data from the Stockinger group on AHR in mice to advance our understanding of intestinal physiology and the critical functions of AHR/Spineless that are conserved across species.


Using genetics, neurophysiology and longitudinal data to disentangle the complex relationship between sleep and mood disorders.
Emerging evidence suggests that sleep traits could be useful indicators of risk, relapse and potential treatment targets for mood disorders. However, the longitudinal and genetic relationships between sleep and mood disorders are complex and remain poorly understood. In this fellowship, I will address these gaps and build on my previous work by using cutting edge methods in genetic epidemiology, sleep neurophysiology and longitudinal data analysis.

Key goals:

(1) Determine the neurophysiological correlates of genetic liability to sleep traits and mood disorders using polysomnography – the gold-standard objective measure of sleep. Examining this in healthy populations will circumvent medication effects and bidirectionality, major confounds in existing polysomnography research.

(2) Examine genetic and longitudinal relationships between adolescent sleep and depression to determine whether genetic variants for sleep traits in adult populations also influence sleep in younger populations, and delineate prospective associations between sleep and depression onset.

(3) Investigate whether sleep disturbances can be used as an indicator of liability to relapse in bipolar disorder. Using in-depth longitudinal data from digital technologies will elucidate the role of sleep in predicting mood episodes in bipolar disorder.

This work will inform sleep interventions and further knowledge on the role of sleep in mood disorders.


Molecular mechanisms actin(g) on endosomal sorting The process of endosomal sorting, where internalised transmembrane proteins (cargoes) are sorted for lysosomal degradation or recycled back to the cell surface, maintains and regulates the cell surface proteome. Thus, endosomal sorting regulates numerous cellular processes including cell signalling.

A fine-tuned amount of endosomal branched actin is required for recycling of cargoes from endosomes to the cell surface. Yet the mechanistic roles of endosomal actin in this process are not understood. Moreover, cargo such as the beta-2 adrenergic receptor (beta2-AR), signal in actin-decorated endosomal recycling domains, suggesting that endosomal actin plays a role in both endosomal recycling and signalling. My project aims to determine the mechanistic and physiological roles of endosomal actin.

I will focus on the major endosomal actin polymerisation machinery – the Arp2/3 activating Wiskott–Aldrich syndrome protein and SCAR homolog (WASH) complex. I will investigate the intrinsic regulation of the WASH complex and how external factors it recruits, cumulatively regulate polymerisation of endosomal actin. Furthermore, I will develop new tools including blocking nanobodies and in vitro reconstitution. In combination, these multi-disciplinary approaches will establish a mechanistic and quantitative model of the role of endosomal actin in sorting and signalling. This will further our mechanistic understanding of endosomal recycling.


Revealing microstructural pathology in Parkinson's disease with super-resolution MRI Parkinson’s disease (PD) is diagnosed by a clinical examination which typically comes 20 years after the initial symptoms. By this time approximately 70% of vulnerable dopaminergic neurons in the substantia nigra (SN) have already been lost. The nigrosomes (small clusters of dopaminergic cells in the SN) have differential histopathological features which make them ideal targets for detecting and monitoring PD.

MRI is highly sensitive to the pathological iron accumulation in the nigrosomes, which is a hallmark of the earliest stages of PD, but quantitative imaging on this sub-millimetre scale is beyond the limits of traditional techniques. I have developed a non-traditional approach to MRI, based on super-resolution approaches from optical microscopy, which can surpass these limitations and rapidly generate quantitative images of the nigrosomes in vivo. I will develop this as an accurate measure of iron accumulation in PD.

The aims of this fellowship are:

 Producing accurate microstructural maps at sub-millimetre resolution
 Modelling and correcting for subject motion
 Testing the hypothesis that microstructural MRI measures in the nigrosomes distinguish PD subjects from healthy controls

If successful, this would enable PD diagnosis in its earliest stages, and maximise the likelihood of finding an effective therapy.


Understanding host restriction following bacterial phagosome rupture Professional phagocytes engulf bacteria inside phagosomes that mediate cargo degradation via lysosome fusion. Some intracellular pathogens evade this fate by disrupting the phagosomal membrane, which triggers antibacterial autophagy. While autophagy may eliminate bacteria for host defence, more recent studies have demonstrated that autophagy can also promote intracellular bacterial survival or be irrelevant for bacterial restriction. Recently, Endosomal Sorting Complex Required for Transport (ESCRT) proteins have been shown to repair small membrane disruptions, potentially providing an alternative pathway for bacterial restriction. The interplay between autophagy and ESCRT machinery during phagosomal damage, the factors triggering each pathway and their contribution to intracellular bacterial killing are poorly understood.

Using the important human pathogen Staphylococcus aureus, I will:
(1) investigate the interplay between autophagy and ESCRT machinery;
(2) identify novel bacterial components that modulate autophagy and ESCRT recruitment; and
(3) uncover unknown host regulators of autophagy, ESCRT and cell-autonomous immunity.

To complete these objectives, I will use high-resolution microscopy to follow bacteria recruiting autophagy and / or ESCRT machinery at the single bacterial cell level. Additionally, I will use high-content genetic screens to discover novel bacterial (using transposon libraries) and host factors (using CRISPR/Cas9) shaping host-pathogen interactions.


The systems biology of oncogenic PI3Kα-driven stemness regulation  Cancer stemness is linked to therapy resistance and metastasis. Emerging evidence suggests that PIK3CA-H1047R, a hotspot mutation in breast cancer and the PIK3CA-related overgrowth spectrum (PROS), elicits a stemness phenotype characterised by dedifferentiation and cell plasticity. Nevertheless, PIK3CA-H1047R does not cause malignancy in PROS, perhaps reflecting molecular differences between mammary (cancer) and endothelial (PROS) cell lineages.

By learning and applying novel systems biology tools, I aim to address the mechanism(s) behind PIK3CA-H1047R-driven stemness in a quantitative manner, taking into account cell type, genetic mosaicism and the strength of genetic PI3K pathway activation. I will generate mosaic cell models with doxycycline-inducible PIK3CA-H1047R expression, focussing on human breast epithelial cells and human endothelial cells due to their relevance for breast cancer and PROS, respectively. The cells will be exposed to short- and long-term PIK3CA-H1047R expression, followed by temporal assessment of: 1.Cell-state-transitions by single-cell RNA sequencing; 2.PI3K signalling dynamics by candidate-based quantitative single-cell imaging. Next, I will use data integration and mathematical modelling to infer the underlying regulatory principles. My ultimate goal is the identification of PIK3CA-mutant- and cell type-specific pharmacological therapies for reversal of aberrant stemness regulation, followed by validation in physiologically-relevant 3D models based on the established mosaic cell systems.


Artificial intelligence for rapid epidemic analysis The aim of this fellowship is to accelerate detection of and response to infectious disease outbreaks, particularly where surveillance, diagnosis, and control are under-resourced.

My first goal is to develop and validate machine learning methods to rapidly infer outbreak properties. I have demonstrated proof-of-concept for this approach, and I expect to be able to train machine learning models on synthetic outbreak data to infer outbreak properties almost instantaneously from data. By building on this approach, understanding its validity and weaknesses from application to historical data, and creating a database of simulations and trained models, I hope to allow outbreak data to be interpreted more quickly and simply than currently possible.

My second goal is to complete and test—first against historical data and then prospectively—algorithms for aetiological identification of outbreaks. These algorithms have the potential to allow outbreaks to be detected and controlled faster, as well as to improve guidelines for syndromic surveillance.

Finally, I plan to integrate these analytics for outbreak identification and analysis into lightweight software tools. After testing them in collaboration with field epidemiologists, I hope to enable public health officials to take advantage of epidemiological insights with minimal training, supporting capacity of public health systems.


Leveraging genealogies for powerful inference of evolutionary processes driving human genetic diversity I will develop powerful statistical methods that leverage estimated genealogies to reveal the key processes driving human genetic diversity and how these have evolved over time. Genealogies have the potential to transform how we analyze genomes, by providing a single framework for addressing a broad range of population and statistical genetics questions, and by substantially increasing power compared to conventional approaches.

I have four key research aims that will impact distinct areas. Firstly, I will develop a novel method for uncovering how genetic structure changes through time and along the genome. This method can uncover unknown ancestral groups; for example, I will characterize previously-reported deeply diverged ancestry of unknown origin in the genomes of modern Africans. Secondly, I will develop a framework for incorporating ancient genomes of diverse ages and data quality into genealogies of modern individuals, enabling the direct study of how ancient and modern genomes interrelate. Thirdly, I will study the evolution of complex human traits through time under various modes of selection, to explain genetic architectures observed in genome-wide association studies. Fourthly, I will investigate the evolution of the molecular mechanisms of recombination, a key driver of human genetic diversity and hybrid incompatibility.


Determining the role of placental endocrine function in the development of gestational diabetes mellitus and its maternal metabolic long-term health consequences  Gestational diabetes mellitus (GDM) is a serious and common pregnancy complication that can evolve in type-2 diabetes (T2DM) years after delivery. Placental hormones have wide-ranging effects on maternal physiology, including the regulation of glucose metabolism. However, we lack information on whether placental hormones could drive changes in maternal metabolism that leads to GDM and the subsequent progression to T2DM. This fellowship aims assess this by using a newly-developed genetic mouse model of placental endocrine malfunction. This is achieved by selectively disrupting the expression of the imprinted Igf2-H19 locus in the placental endocrine cells. Using this approach, I obtained data showing that mice with placental endocrine malfunction have metabolic disturbances, including high blood glucose concentrations during pregnancy. Also, these females show changes in their metabolism in the months after delivery. This project will further these findings in the model by using state-of-the-art in vivo metabolic tests and use transcriptomics, proteomics and methylome analyses to identify how placental hormones induce changes in maternal tissues that cause metabolic problems during and after pregnancy. My long-term aim is to identify biomarkers that could be explored as diagnostic tools or therapeutic targets to prevent the development of GDM and T2DM.


Impact of autophagy on lymphocyte stemness Efficient T cell responses rely on heterogeneity, characterized by the rise of effector and memory cells. Autophagy, responsible for homeostatic degradation and recycling of cell cargo, is crucial for T cell differentiation. Upon ageing, autophagy is impaired, which is detrimental for the generation of memory cells retaining stemness. Interestingly, I have observed that naïve CD8+ T cells from aged mice are unable to undergo asymmetric cell division (ACD) (unpublished). ACD is a conserved mechanism to generate diversity, by endowing daughter cells with different fate determinants. As both autophagy and ACD are involved in T cell differentiation and impaired upon ageing, unravelling how they synergistically influence T cell stemness is at the centre of this project. We propose to use state-of-the-art imaging, proteomics, and metabolomics to investigate whether autophagy impacts cell asymmetries upon T cell mitosis. Functional validation will be addressed by using the novel combination of autophagy-deficient and organelle-tagged cells (SnapTag mice), which will enable us to evaluate whether asymmetry inheritance of cell cargoes leads to asymmetric fates in vivo. We anticipate that this research will be relevant to better understand how stemness is coordinated, and potentially lead to the development of therapeutic strategies in the context of regenerative medicine.


Spatial and temporal regulation of immune specific myosins and their role in neuroinflammation Unconventional myosins of class I can directly associate with membranes, thereby providing a dynamic link between the actin cytoskeleton and the plasma membrane or intracellular organelles. Immune cell-specific myosin 1F and myosin 1G (MYO1F and MYO1G respectively) have roles in immune cell migration and regulation of membrane tension. Studies show both motors are upregulated in microglia during neuroinflammation. To uncover the temporal regulation of these motors, a number of biophysical assays will be employed, such as in vitro motility assays, optical trap experiments and stopped-flow spectroscopy. The molecular interactions of MYO1G that determine cellular function will be explored using a combination of proteomics and cell biological assays to identify the motors’ interacting partners and elucidate its spatial regulation in vivo. The effects of two distinct phosphorylation sites on motor domain activity of MYO1G will be explored with mutations to mimic the non- and phosphorylated states. Protein crystallography studies of MYO1F and MYO1G will enable the design of small molecule inhibitors using structure-based in silico screening, with the ultimate goal to treat neuroinflammation in humans. Taken together these approaches will elucidate the cellular and physiological role of these motors and uncover the potential use of MYO1F and MYO1G as therapeutic agents.


Perceiving people from voices

Perceiving people from voices When hearing voices, we can perceive a wealth of information about the speakers, such as their identity, regional background, and age. This project will investigate how listeners achieve this, thus probing fundamental mechanisms of person perception from voices. To achieve this, I will take a broad perspective to integrate the usually distinct fields of identity perception and the perception of other speaker characteristics.

Through a programme of behavioural research using acoustic signal processing and methods from the statistical or distributional learning literature, I will first explore how listeners form representations of voice identities through a programme of training studies: What is the acoustic content of mental representations of voices? What kind of information is encoded in such representations?

I will then extend these findings from voice identity perception to the perception of other speaker characteristics: Are such population-level representations formed based on similar mechanisms to identity representations or are there differences?

Finally, I will conduct a magnetoencephalography (MEG) study to describe the timecourse of person perception from voices: Which speaker characteristics are decoded by listeners at which point during perception? Does familiarity with a person change the processing of that voice? Can the low-level acoustic properties (partially) explain the timecourse?


Effective analysis and experimental design for CRISPR screens with scRNA-seq readout Understanding how cell fate decisions are regulated is a key question in molecular biology. Building on the CRISPR revolution, exciting technologies (e.g., CROP-seq or direct capture Perturb-seq) induce a genetic perturbation that is characterised, alongside the transcriptome of the cell, by single-cell RNA-sequencing. This enables a range of experimental designs that can, in principle, shed light on the transcriptional response to gene perturbations, its pathogenic and non-pathogenic variation, and the role of gene regulation during differentiation.

However, current computational methods do not exploit this potential: in particular, the ability to accurately measure the effect of a given perturbation is lacking, and the potential to efficiently explore the space of all possible perturbations and conditions remain untapped.

To address this, I will develop a comprehensive suite of computational tools (i) to infer transcriptomic effects of gene knockouts unconfounded by perturbation efficacy, (ii) for optimal experimental setup to increase insights gained from experiments and improve their scalability, (iii) to identify differences in gene regulation across individuals, and (iv) for the study of knockout effects during differentiation. This will lead to an improved understanding of gene regulation, its variation across individuals, and to improved differentiation protocols, with important consequences for cell therapy.

Clustered Regularly Interspaced Short Palindromic Repeats


EAT Foundation - Bridge Funding

Discretionary Award - OPOH

EAT Foundation - Bridge Funding  With the support from Wellcome Trust during the years 2016-2019, EAT  achieved important results. The EAT SFF is globally recognized as a meeting place for  stakeholders to shape the future of food. The EAT-Lancet Commission  changed the debate around food, environmental sustainability and health, and the scientific targets set by the Commission for healthy diets within safe planetary boundaries are  guiding action by a wide range of actors across policy, business and civil society. EAT is  catalyzing  action through a number of collaborations, such as with C40, influencing food system policy agendas in  50 cities around the world. The GBP200,000 contribution from Wellcome Trust for 2019 will secure EAT’s ability to continue its efforts and avoid delay or disruption of its work, while working with Wellcome Trust ito develop a Phase 2 program.
EATrecognizes that there is an urgent need to undertake a proactive and strategic organizational review. This review will guide EAT in addressing weaknesses in its financial, operational, fundraising and reporting functions that have exposed risks that must be mitigated prior to the end of 2019 The review will provide a clear pathway to ensure financial and operational sustainability whilst supporting EAT’s agility within focused and strategic structures.


Innovations Psychosis Flagship

Science, Innovation and Translation Programme Advisory Group

Mr Colm Healy, Prof Barnaby Nelson, Prof Stan Zammit, Prof Tyrone Cannon, Dr Diana Perkins, Dr Robert Whelan, Dr Clark Jeffries, Dr Melanie Foecking, Prof Bryan Morgan, Prof Mary Cannon, Prof Patrick McGorry, Prof Philip McGuire, Dr David Mongan, Dr Gerard Cagney, Dr Meike Heurich, Prof G. Paul Amminger

IMPETUS: Investigating Markers derived from Proteomics for Estimation of Transition from the Ultra high-risk State to psychotic disorder Mental disorders such as schizophrenia are among the most expensive disorders in
terms of quality of life and societal cost. Early identification and intervention is
associated with improved outcome and is facilitated by targeting those at clinical-highrisk-
for-psychosis (CHR) as up to 25-30% develop psychotic disorder (PD) at 6 year
follow-up. There is growing evidence for the involvement of the immune system and
inflammation in this disorder. We have added to this literature by demonstrating that
the complement pathway, the blood plasma component of the innate immune system is dysregulated in blood samples of individuals at age 11, many years before these
individuals report symptoms in keeping with psychotic disorder at age 17.
Based on our own plasma proteomic data and machine learning analyses, we now
have evidence for a set of biomarker proteins which can predict transition from the
CHR to PD with a high degree of accuracy. We now seek to refine and replicate these
findings.
Our study: Using state-of-the-art proteomic methods and machine learning approaches
we will replicate and refine this biomarker signature of transition from CHR to psychotic
disorder in three distinct international samples and one longitudinal cohort with a total
CHR sample size of over 1000 CHR subjects. We will also undertake functional assays
that measure plasma protein levels of the complement and coagulation pathway and
their activation fragments as indicators of complement and coagulation dysregulation.
Our study includes commercial diagnostic/prognostic biomarker expertise.


Making social change happen: What inspires collective action for health and gender equality? Motivation: Interventions mobilising communities in collective action for their own health are some of the most effective known global health interventions. However, they do not always succeed and we cannot presently predict or explain why this happens.

Aim: Taking as an example a community mobilisation programme to prevent violence against women in urban slums in Mumbai, India, I will test theory concerning the drivers of collective action from behavioural economics and social psychology.

Method: (1) To unpack how a community mobilisation programme may stimulate collective action in urban India, I will collect and analyse qualitative interview, media and observational data.

(2) To uncover the determinants of participation in collective action, I will conduct cross-sectional and difference-in-differences analysis of secondary data from a randomised controlled trial of the same community mobilisation programme.

(3) To produce causal evidence for the drivers of collective action, I will conduct a behavioural experiment to test the behavioural effects of changing key messages on programme participants. I will use the answers to (1) and (2) to guide message design.

Impact: The study results will be able to guide policy-makers and practitioners on when, how and why complex participatory interventions work to promote health and gender equality.


Sir Henry Wellcome Postdoctoral Fellowship

The evolution of mobile genetic elements in Gram-negative bacteria I will explore how structural variation can be used to understand the evolution of antimicrobial resistance (AMR) on mobile genetic elements (MGEs).

Most previous research is biased towards nucleotide-level variations in the core genome (high-effect SNPs). Now, the availability of complete genomes means that resolving the larger structural variation of MGEs is both possible and increasingly relevant for the spread of AMR. I will develop a framework to model the non-mutational processes which generate this variation, then apply this to the linked evolution of MGEs and their ‘host’ genomes.

During this fellowship, I will sequentially:

 Aim 1. Develop a tool to quantify structural variation and resolve common blocks around the flanking region of AMR genes, which I have previously shown can be used for phylogenetic reconstruction.
 Aim 2. Apply this to longitudinal datasets and obtain rate estimates for non-mutational processes.
 Aim 3. Investigate the compensatory evolution of MGEs as they move between genomic backgrounds.

Two major applications will be:

 Application 1. Small transposons, leading on from my pioneering work on the mcr-1 transposon.
 Application 2. Clinical class 1 integrons, which carry multiple AMR genes.

This proposal tackles questions of fundamental importance for the evolution of flexible genomes.

Grants awarded from 1 October 2005 to 30 June 2021


PhD Training Fellowship for Clinicians

The NCEMA study: Neutrophils in Cerebral Malaria  Every year half of the world’s population is at risk of getting malaria, caused by the Plasmodium parasite, and almost half a million people die; mostly children in sub-Saharan Africa. Some infected children are at a higher risk of death since malaria can damage their brains as part of a severe complication called cerebral malaria (CM). Neutrophils are one of the first lines of defence against fighting infections by damaging cells, yet their involvement during CM is not entirely understood.

We hypothesise that neutrophils interact with Plasmodium affecting the blood vessels of the brain and initiate or promote the progression to CM. We aim to perform a detailed analysis of the role of neutrophils in CM, using prospectively collected blood from children with CM, archival post-mortem brain tissue, blood vessel cell cultures and a mouse model. With the exception of the mouse model our project will be based in Malawi, a country endemic for malaria.

Our findings will allow us to understand if neutrophils cause damage to the brain blood vessels leading to CM. This could provide the basis of a search for novel prevention and treatment strategies that can potentially decrease the high rates of death of this disease.


Discretionary Award – C&S

Exploring Science Pedagogy with Teacher-Led Randomised Controlled Trials (RCTs)

   The collaboration between Education Development Trust (EdDevTrust) and the National STEM Learning Centre (STEM Learning) will enable 60 highly trained and competent science teachers to access a unique approach (‘Test and Learn’) and set of tools to guide and support them to carry out their own rigorous classroom-based research. Teachers will test the evidence-based theories, approaches, pedagogies and policies introduced to them through STEM Learning’s CPD programme using randomised controlled trials, applying scientific method to explore science pedagogy.


Discretionary Award – C&S

Research-2-practice: Research-informed science lesson plans for busy teachers Spoke with Ruba Aljarf today (9 November 2019) and she said to simply upload the attachment.


Science Teacher Journal Clubs

Discretionary Award – C&S

Science Teacher Journal Clubs Our project will support science teachers to engage with research through a ‘teacher journal club’ (TJC) approach, building on work in both education and in the medical sciences, where journal clubs are a well-established approach to CPD. As well as providing cost- and time-efficient CPD that adheres to the principles of effective learning for teachers, journal clubs are by their nature focused on helping teachers to engage effectively with research evidence. This project proposes to apply the principles of successful journal clubs from medicine to education. The journal clubs will exclusively be online and journal clubs facilitators and participants will receive online training before their first TJC. This online training will cover the background of TJCs and how it relates to effective teacher CPD, research appraisal and journal club facilitation skills. The project will take a 'fading scaffolding' approach where the support for TJC facilitators will fade over time with the goal for them to run TJC independently by the end of the project.


Discretionary Award – C&S

Learning by Doing (research engagement through evidence-informed lesson plans)) Our project aims to increase teachers’ engagement with and use of research through the provision of teaching resources – a comprehensive program of work, including adaptable lesson plans – and training in their use. The lesson plans will be designed based on research evidence and will also contain annotated summaries of relevant research evidence with links to the underlying research. The training will help teachers understand how and why to engage with research evidence by using the lesson plans, and will be participatory in nature. Training will occur three times throughout delivery to remind teachers to engage with evidence.  The intervention will pertain to a particular unit of year 8/9 physics e.g. forces.  We will recruit physics teachers at a diverse mix of UK state-funded schools to test our resources.

In our approach, engaging with research and learning how to embed it in practice will be made extremely easy for teachers, which is the most effective way to increase the prevalence of desired behaviour (and is especially important in the context of an already overburdened workforce). In particular, this approach will address potential intention-action gaps between teachers engaging with research evidence and actually applying it in their teaching practice.


PhD Training Fellowship for Clinicians

 Participatory Approaches in Mpemba for Developing Clean Air interventions (PAMODZI) Air pollution is a major health risk worldwide, particularly in countries such as Malawi where smoke is widespread, both indoors and outside, and populations remain reliant on polluting fuels for cooking and heating. Research so far, largely using ‘improved cookstoves’, has failed to demonstrate the hoped-for health improvements in lung health.

This study brings together the priorities of the research team with those of the communities which the research aims to benefit, from the start. I will use participant observation to explore the role of smoke in the context of a Malawian village, also measuring individuals’ smoke exposures as they go about their daily lives. Working with community members we will then use this information to develop a set of acceptable, context-appropriate clean air interventions. Finally, I will assess the effectiveness of these interventions in reducing smoke exposure through a small village-based trial.

The study will build on the knowledge of members of the village, raising awareness of the issues and including participants in developing solutions from the start. This will assist in developing an effective, sustainable clean air intervention, as well as demonstrating a more engaged approach to Global Health research.


Joint Health Systems Research Award

Joint health systems research initiative

Joint Health Systems Research Award – round 6 – 2019 N/A


Epidemiology and outbreak prediction of yellow fever virus Yellow fever virus (YFV) outbreaks are escalating worldwide despite the existence of a vaccine. Global travel raises the chance that YFV will become established in Asia, where populations are not vaccinated and an outbreak would be catastrophic. Our ability to predict and control YFV outbreaks is reduced by our lack of knowledge about (i) transmission of YFV in its sylvatic reservoir (non-human primates) and (ii) how YFV escapes from this reservoir to spread amongst people in urban areas. Severe under-reporting in both humans and non-human primates hampers our ability to directly study YFV transmission behaviour. Recent advances in portable genome sequencing and virus genomic epidemiology (including phylodynamics) offer new opportunities to use virus genomic data to reconstruct unobserved outbreak dynamics, even when sampling is sparse. I will combine these techniques to improve our understanding of YFV epidemiology, by: (i) integrating viral genomic data into newly-refined YFV mathematical models for improved outbreak prediction; (ii) implementing phylodynamic approaches to identify drivers of sylvatic transmission, and; (iii) exploiting new strategies to generate virus sequences from traditionally neglected times and locations. My Fellowship research findings will improve YFV outbreak prediction and contribute to the development of refined vaccination strategies.


PhD Training Fellowship for Clinicians

VAPRE: Exploring the Relapse Prodrome of ANCA associated Vasculitis ANCA Vasculitis is a rare autoimmune disease, whereby the immune system is triggered to self-destruct – the systems normally primed to fight infection and cancer cells are incorrectly activated, resulting in organ destruction, such as kidney failure.
Like most autoimmune diseases, ANCA vasculitis goes through periods of remission (quiet) and relapse/flare (active). Half of patients will experience a flare over 5 years, resulting in cumulative tissue damage, due to the destructive inflammatory process itself and the powerful medications required. Infection is an unwanted complication.
The exact cause of ANCA vasculitis, and indeed autoimmunity, has yet to be discovered. Evidence suggests it is complex interaction between a person’s genetic make-up and unknown triggers in their environment. We aim to identify these triggers, enabling us to predict autoimmune disease risk and hence explore avoidance mechanisms and personalised treatment options.
This project will utilise a novel big data approach, bringing together physicians, patients, computer scientists and artificial intelligence expertise to create an iterative model that learns over time about the impact of the environment on disease flare. Our ultimate goal is to create a clinical tool that will indicate flare risk for a particular patient, at a given point in time.


Discretionary Award – C&S

British Academy Small Research Grant, Conference and Policy Workshop Proposal The British Academy is submitting a funding proposal to the Wellcome Trust which will provide support for researchers in the humanities and social sciences working in areas related to health and wellbeing.  Taking a broad definition of health, the proposal will provide a  portfolio of support for academics, at all stages of their careers, working in the humanities and social sciences by providing funding for Small Research Grants, academic conferences and policy workshops.  The proposal follows discussions with the Trust over a number of months and is valued at £3.97 million including: funding of £2.76 million for Small Research grants; £1.12 million for conferences; and £84,000 for policy workshops (over 3 years).  Funding is proposed to begin in early 2020 and to finish in 2026. The collaboration is designed to demonstrate the relevance of humanities and social science research in relation to health and wellbeing through the scale and breadth of funding options for researchers and the potential for long term impact.


Discretionary Award – C&S

Teacher Research Grant - Scoping Phase, Evaluation This grant will support both Sheffield Hallam University and the National Foundation for Educational Research (NFER) to work with the four grantees of the Teacher Research Scoping Grants and to undertake the writing and costing of the proposal for the research and evaluation study of this programme.


PhD Training Fellowship for Clinicians

Maximising T cell cytotoxicity and persistence for long term anti-cancer protection in adoptive cell therapy (ACT). One of the functions of the immune system is to recognise and kill cancerous cells.  This is done by specialised immune cells called cytotoxic T cells.  However, there are many ways in which this process can go wrong, and this leads to the development of cancer.  Many recently developed treatments for cancer are designed to improve the ability of the T cells to recognise and kill the tumour cells, but this is still imperfect and there is lots of room for improvement.  I aim to make alterations to the signals that occur inside T cells after they "see" an abnormal tumour cell, in order to make them more effective at killing cancer cells and to stay around and do this job for longer.  I will test modifications by making relevant alterations to T cells in the lab, and then assessing their ability to kill cancer cells in a petri dish and to destroy tumours in mice with cancer.  Different modifications will enable me to understand how T cells function, and where modifications can be made to improve their tumour killing function.  This could be used in future to modify patients’ own T cells to treat their cancer.


PhD Training Fellowship for Clinicians

Establishing the role of Staphylococcus aureus RNA-binding proteins in regulating host adaptive responses and antibiotic resistance. Staphylococcus aureus is a major human pathogen associated with thousands of deaths each year. S. aureus can adapt to survive and thrive inside human immune cells (macrophages) and has developed resistance to multiple antibiotic classes making it a dangerous pathogen.  We hypothesise that S. aureus uses the interactions between proteins and RNA to control the adaptation to surviving inside human macrophages and to avoid being killed by antibiotics.

We will assess how the pathogen changes which proteins are bound to RNA when exposed to environmental challenges including those seen in human infection and antibiotic treatment. We will assess how these changes occur in the whole organism and in specific key proteins. We aim to engineer bacteria which have proteins which can’t properly bind RNA and to see if they are less fit to survive in simulated infection, when infecting human immune cells, in an insect model of infection and when exposed to antibiotic therapy.

The identification of critical pathways involved in the adaptation of S. aureus to the host environment may reveal new therapeutic targets for the control of infection.


Innovations Psychosis Flagship

Using Neurofind to make individualised inferences in first episode psychosis: feasibility, acceptability and clinical utility in a real-world setting Brain-based disorders, including psychiatric and neurological illnesses, represent
10.4% of the global burden of disease. At present, there are no established imagingbased
tests for detecting these disorders, monitoring their progression over time and
optimising treatment. In a previous Wellcome Innovator Award, Prof Andrea Mechelli and team at KCL developed Neurofind - a user-friendly web-based tool, which usesdeep learning technology to quantify neuroanatomical abnormalities from structural Magnetic Resonance Imaging scans. This tool compares an individual scan against a
reference database and generates an individualised report that could support
diagnostic, prognostic and treatment decisions in individual patients. In this follow-on
award, the feasibility, acceptability, safety and clinical utility of Neurofind will now be
assessed in a real-world setting. Neurofind will be tested in patients with first episode
psychosis recruited from the South London and Maudsley NHS Foundation Trust.
The study aims to test if Neurofind is feasible, acceptable, safe and if the information
in the individualised patient reports it produces is predictive of clinical outcomes at 6-
months follow-up. If successful, the proposed trial will lead to the adoption of
Neurofind in real-world clinical services, with tangible benefits for patients, clinicians and service providers


Discretionary Award – Innovations

Determining Preferred Product Characteristics to Support Uptake of Innovative Antibodies Through this project, IAVI and WHO Immunizations, Vaccines, and Biologicals (IVB) will harness input from a broad network of stakeholders to produce a Preferred Product Characteristics (PPC) technical document for forthcoming monoclonal antibodies (mAbs) for HIV prevention. Created early in clinical development and with attentiveness to end-user and health systems perspectives, this PPC document will provide strategic guidance as to preferences for new HIV preventative antibodies to inform clinical development and support eventual integration into WHO policy. While the focus of this effort will be on articulating optimal product attributes for antibodies for HIV prophylaxis, it is anticipated that acceptability, suitability and feasibility criteria identified through this process can inform product design, clinical development, and access considerations for a broader array of antibody-based products for infectious and neglected diseases in the pipeline.


PhD Training Fellowship for Clinicians

Investigating the crosstalk between adipocytes and macrophages during wound repair Our immune system exists to help our bodies fight infection, heal wounds and remove unhealthy cells. In order to gain as much information as possible about this complex system, it is vital to investigate immunological processes in the context of a living animal. Despite evolutionary divergence from humans, the fruit fly Drosophila melanogaster contains a relevant immune cell type, making it an ideal model in which to investigate immune cell functions, such as damage signalling, cell corpse recognition and immune cell memory.

It has recently emerged that fat cells also play a role in wound healing, and this project seeks to elucidate the mechanism by which fat cells contribute to the immune response. The tractable genetics of Drosophila will allow us to identify potential candidate genes by screening for which genes are "turned on" in cells that are responding to laser induced wounds. We will then increase or decrease the level of expression of these candidate genes and use real time imaging in the living Drosophila pupae to identify the effect that these genes have on immune cell and fat cell migration to wounds.


PhD Training Fellowship for Clinicians

Spatial regulation of core neurodevelopment transcription factors in human glioblastoma stem cells The most common brain cancer, termed glioblastoma (GBM), is incurable and life expectancy is only ~14 months.  The cells that drive GBM are trapped in a stem cell-like state and exploit pathways used by normal brain stem cells.  GBM stem cell-like cells increase key factors (transcription factors) that are master regulators of brain stem cells, such as SOX2 and FOXG1, which bind to gene control regions called super-enhancers. Many critical genes that drive GBM exist as separate pieces of DNA rather than as part of the organized DNA structure in chromosomes, called extra-chromosomal DNA (ecDNA).  This enables tumour cells to rapidly expand key regulators and may contain super-enhancer areas to switch important genes on.

We predict that increased amounts of these transcription factors and their clustering at super-enhancers explains the locked-in stem cell state of GBM cells.

This project aims to confirm that important gene drivers of GBM are found on ecDNA in GBM cells from patients. We will test which transcription factors stick to which enhancers to understand the combinations needed to switch on important genes.  We will evaluate if these factors, enhancers and genes physically converge as condensates to make cancer cells ‘stuck’ in their stem cell-like state.

Grants awarded from 1 October 2005 to 30 June 2021


PhD Training Fellowship for Clinicians

How do dysfunctional endothelial cells in cerebral small vessel disease modulate surrounding oligodendroglia through secretion of heat shock protein 90 alpha? Dementia is becoming an increasingly important disease, affecting vast numbers of people. Disease of the small blood vessels in the brain is the second most common cause of dementia, and is called cerebral small vessel disease. The endothelial cells which line the blood vessels start the disease process and then affect the surrounding brain cells causing the problems we seen in patients with dementia. I will study how endothelial cells cause disruption to the surrounding brain cells and whether it can be reversed, leading the way to potential treatments for small vessel disease.


PhD Studentship (Basic)

Investigating how winners alter losers in Minute cell competition I work on cell competition, a process where relatively less fit cells (losers) are eliminated by relatively fitter neighbouring cells (winners). There are many types of cell competition and in my PhD I will focus on Minute cell competition. In Minute cell competition cells that have lost one copy of a ribosome gene (called Minute) are induced to die by wild-type cells. Minute cell competition acts as a quality control to maintain tissues healthy and is likely to contribute to the elimination of cells with tumorigenic potential. We are interested in understanding how proximity with winner cells modifies the cellular state of Minute cells so that they behave as losers and die. Our approach involves introducing groups of wild-type-cells in a Minute background in developing fly epithelia. In my work I will characterise how cell competition changes specific cellular processes such as translation, autophagy and oxidative stress. I will also look at gene expression changes induced during cell competition in loser Minute cells, to identify novel additional factors affected by winners and involved in cell competition. This work is likely to identify new components that, by modulating cell competition, could be important in maintaining tissue health and in cancer prevention.


Senior Research Fellowship

Using genetics to understand causal mechanisms underlying adverse outcomes of obese pregnancies More than 1 in 5 UK pregnant women are clinically obese, a condition associated with heterogeneous health outcomes for mother and baby. Only limited understanding of the associations (e.g. gestational diabetes and high birth weight, hypertension and preterm birth/low birth weight) has been possible in traditional observational studies due to complex interrelated exposures and outcomes. My research will use human genetics to dissect causal pathways and understand how a higher maternal BMI can lead to such diverse outcomes. I hypothesise that maternal effects on fetal growth and gestational duration are moderated by fetal genetics. My first aim is to understand how a fetus regulates its own growth and gestational duration in different maternal environments. We will apply results of new genome-wide association studies of placental weight and umbilical cord insulin to give mechanistic insights. My second aim is to understand how raised maternal BMI impacts gestational duration and growth, and my third aim is to examine whether fetal genetics can influence the maternal environment. By identifying causal mechanisms, this fellowship will be an advance towards better targeting of antenatal healthcare and advice to pregnant women, according to their level of risk to reduce the incidence of adverse pregnancy outcomes.


Investigator Award in Science

Interlocking nanomechanics of kinesins and tubulins Kinesin-microtubule systems transport intracellular cargo in eukaryotes and are essential for life. Recently, we discovered that dynamic microtubules can respond to kinesin by changing their conformation, lattice spacing, curvature and stability, and conversely that kinesin stepping can sense and respond to conformational shifts in the microtubule lattice. These insights fundamentally redraw our picture of the function of kinesin-microtubule transport systems. I now propose to dissect the mechanical mechanisms by which kinesins and microtubules instruct one another, using protein engineering combined with single molecule optical trapping at unprecedented resolution. Working with both wild-type and mutant kinesins and tubulins, principally from S. pombe, we will determine the structural requirements for different microtubule lattices to control kinesin substeps, backsteps and bidirectionality; and the converse requirements for kinesins to manipulate the conformation and fate of microtubules. Our experiments will reveal how tubulins communicate mechanically with one another and with kinesins. Illuminating the molecular mechanisms of active mechanical feedback in kinesin-microtubule systems will transform understanding of the transport machinery and open the way to improved chemical biological manipulation of its in vivo function.


Senior Research Fellowship

The Intergenerational Transmission of Mental Health Problems: Identifying Causal Pathways and How to Interrupt Them I propose to use my SRF to investigate the intergenerational transmission of mental health problems. Previously, in my Sir Henry Dale Fellowship, I have developed statistical models for use with genetically informative intergenerational data (composed of many extended families) for use in distinguishing genetic transmission from the potential causal effects of parent on child. In my SRF I will build on this work:

1. I will establish to what extent the treatment of mental health problems in parents reduces the transmission of problems to children (and vice versa).

2. Combine pedigree-based approaches with genomic data to draw on the strengths of each. This will enable the identification of the direction and magnitude of intergenerational causal effects, and identify polygenic scores involverd in gene-environment interplay relevant to the intergenerational transmission of mental health problems.

3. Explore the biases inherent in our use of volunteer based cohorts to understand mental health aetiology.

4. Extend my own children-of-twins study, funded as part of my SHDF, CoTEDS (the Children-of-TEDS). CoTEDS is the second generation of an ongoing twin study, and the first twin study in the world to include information on parents and children from birth.


Collaborative Award in Science

Dr John Marioni, Prof Benjamin Simons, Dr Anna-Katerina Hadjantonakis, Prof Berthold Gottgens, Prof Jennifer Nichols, Prof Shankar Srinivas, Dr James Briscoe

Molecular mechanisms of cell fate decisions in gastrulation and early organogenesis The cell fate decisions that accompany exit from pluripotency and entry into gastrulation and early organogenesis establish the vertebrate body plan. Recent advances in single-cell multiomics have allowed transcriptomes and epigenomes to be mapped at single cell resolution during mouse embryogenesis. These studies suggest that cell fate decisions can be made autonomously, where cell fate derives from an intrinsic regulatory programme, or signalling-based, in which fate is determined by the reception of local extrinsic cues. The potency of precursors is progressively restricted as fate is allocated, but separate developmental routes can lead to convergent cell fates. To understand the fundamental principles of these cell fate determination processes, we will combine in vivo mechanistic studies and quantitative mechanistic modelling. We will integrate cell lineage relationships with spatial information and single cell multi-omics, using (epi)genome editing to perturb cell fate decisions in vivo. By comparing early organogenesis across the three germ layers, we will seek to understand the shared and unique features of the mechanisms that establish the underlying fate map.

Gene Expression Regulation, Developmental


Collaborative Award in Science


Investigator Award in Science

Improved targeting of stroke prevention by enhanced phenotyping of trends, risk factors, symptomatology, aetiology, and outcome: Oxford Vascular Study Having founded the new Centre for Prevention of Stroke and Dementia (CPSD) to allow junior/intermediate colleagues to develop their programmes, my own research will continue to focus on better phenotyping of TIA and stroke and of known risk factors in order to substantially improve the targeting of preventive treatments. My work involves four core themes:

 Understanding the distinct temporal trends in incidence of different stroke subtypes to monitor the effectiveness of prevention and to develop new strategies;
 Obtaining reliable data on prognosis of different TIA/stroke subtypes to better target preventive treatments;
 Having proved the impact of better prediction and prevention of early recurrent stroke, I aim to substantially improve prevention of later recurrent stroke, focussing particularly on the utility of more detailed phenotyping (e.g. identification of occult atrial fibrillation, intracranial stenosis, and PFO, and remote monitoring of home-BP);
 By more detailed assessment of BP I will inform the treatment of hypertension in primary prevention of stroke (by studying long-term pre-morbid BP) and in secondary prevention (home telemetric BP-monitoring);

Taken together the results of this work will impact on the treatment of almost all patients with TIA or stroke (2 million prevalent cases in the UK alone).


Collaborative Award in Science

Dr Gwyneth Card, Prof Gerald Rubin, Prof Scott Waddell, Dr Matthias Landgraf

A high-quality connectome of the complete adult Drosophila central nervous system Building on advances during our successful connectomics collaboration (2016-20), we now propose a very ambitious new goal: a complete, high-quality connectome for the male Drosophila central nervous system (CNS). With Wellcome support and leveraging Janelia’s unique electron microscopy imaging capability, we could turn image data into a fully analysed connectome. This would be the first CNS connectome of an animal with complex motor and cognitive behaviours. In contrast to existing fly datasets, it will be bilaterally complete, include brain and nerve cord and have intact sensory-motor connectivity.

This connectome should have an enormous impact on the understanding of CNS-spanning circuitry underlying complex behaviour. We will publicly release initial draft and high-quality versions as soon as they are complete. We will immediately use it to study multisensory integration, memory recall, decision making, modification of brain states, the flexible organisation of motor behaviour, and sexually dimorphic circuits. It will provide a critical resource for  > 200 labs worldwide studying Drosophila neurobiology (with impacts on developmental biology and molecular cell atlases) and provide new opportunities for theoretical neuroscientists to study complete, biologically-defined neural networks in a richly investigated organism. We expect general principles, applicable to all nervous systems, including those of humans, to emerge.


Senior Research Fellowship Renewal

The fight for success: inter-bacterial competition mediated by the Type VI secretion system and its effectors The Type VI secretion system (T6SS) is used by many Gram-negative bacteria to deliver toxic ‘effector’ proteins into rival bacterial cells as a means of inter-bacterial competition. The T6SS likely plays a central role in shaping many polymicrobial communities, but important aspects of effector delivery and action in target cells, and the ‘real-life’ relevance of T6SSs in a clinical context remain elusive. We will investigate the journey of individual and co-operating groups of effectors, from their recruitment by the T6SS to their fate and action in targeted cells, and dissect the mechanism of individual anti-bacterial effectors. We will also consider the global availability and mobility of anti-bacterial effectors and how the T6SS and its effectors can influence bacterial success in a clinical context. Using multidisciplinary approaches, we aim to:

 Determine the mechanism of toxicity of novel anti-bacterial effectors
 Elucidate the fate of effectors inside target cells
 Define mechanisms of versatile effector recruitment and delivery in attacker cells
 Use genomics to reveal the diversity, evolution and real-life relevance of T6SS effectors

Our findings, combining mechanistic detail with insight into biological relevance, will provide fundamental advances in our understanding of T6SS-mediated anti-bacterial activity and may inform future strategies to counter bacterial pathogens.


Investigator Award in Science

London School of Hygiene & Tropical Medicine

Functional analysis of the downstream mediators of cyclic nucleotide signalling in malaria parasites Our research programme will deliver mechanistic understanding of how cyclic nucleotide signalling controls the development of two key phases of the malaria parasite lifecycle: the asexual blood stage that causes pathology, and gametogenesis that is required for transmission to the mosquito vector. We have previously shown that there is a temporal switch from cyclic GMP (cGMP) signalling to cAMP signalling as the asexual parasite progresses from egress (escape from its host erythrocyte) to invasion. Cyclic GMP signalling also controls egress of sexual stage parasites to enable fertilisation in the mosquito. In both lifecycle phases, egress requires cGMP-dependent calcium flux. We have recently identified a unique, essential membrane-bound binding partner of the cGMP-dependent protein kinase (PKG). We have also identified a set of high confidence targets of cAMP signalling required for invasion and subsequent parasite development, and have obtained exciting new insights into how cGMP production is governed. We now want to: (1) determine the mechanisms underlying the interrelationship between cGMP and calcium signalling; (2) dissect the role of cAMP-dependent phosphorylation in erythrocyte invasion; and (3) identify the parasite proteins that interact with cyclase and phosphodiesterase enzymes (which balance cellular levels of cyclic nucleotide) to understand how the pathways are regulated.


Investigator Award in Science


Investigator Award in Science

Mechanistic investigation of the cross-talk between spliceosomal complexes and polyadenylation factors Splicing and polyadenylation are two essential steps of gene expression that account, to a great extent, for the complexity of eukaryotes. The two processes are catalysed by the spliceosome and the polyadenylation apparatus – two macromolecular machines of megadalton-size which contain more than 70 and 20 proteins, respectively.

The two machines associate physically to form composite assemblies, where cross-talk events support emerging layers of regulation of splicing and polyadenylation. These assemblies are primarily unexplored from a mechanistic perspective, due to their excessive size, complexity and dynamics.

By employing state of the art technologies and our long-standing expertise in the structural biology of splicing, the time is now ripe for a thoroughgoing investigation of these assemblies. Thus, we aim to stall and isolate composite assemblies relevant for: (i) the coupling between splicing and polyadenylation, (ii) the definition of exons during constitutive and alternative splicing and (iii) protection of genes from premature polyadenylation. Afterwards, we will characterise their 3D structures and functions by electron cryo-microscopy and complementary biochemical methods. The proposed research is expected to be eye-opening and bring a substantive contribution to our understanding of how fundamental processes of gene expression integrate mechanistically.


Senior Research Fellowship Renewal

Mechanistic links between morphogenesis and differentiation As cells build the body, they use information from localised secreted signals to guide differentiation and morphogenesis. It is often assumed there is unidirectional flow of information from these biochemical signals to the resulting morphological changes, but this 'linear' model cannot explain how development is orchestrated with such remarkable reproducibility.

We have found that changes in epithelial structure provide a previously underappreciated source of information that feeds back into differentiation decisions by modulating biochemical signalling. Using mouse gastrulation as a paradigm we have identified candidate molecular mechanisms that mediate this feedback: 1) A cadherin-mediated community effect that dampens anti-neural signals to synchronise neural differentiation 2) a cell-clustering process that amplifies juxtacrine pro-mesoderm signalling to coordinate differentiation across collectives of cells.

We propose that these two interlinked mechanisms coordinate distinct sources of information across different time scales. We will test this in vitro and in vivo using a unique toolkit based on molecular and biophysical manipulation of epithelial structure, mosaic analysis, and custom-developed quantitative image analysis software.

Generalisable principles emerging from this work will help resolve the currently unpredictable relationship between signalling-input and differentiation-output to give us better control over in-vitro differentiation, organoid formation, tissue repair, and tumorogenesis.


Investigator Award in Science

Neural mechanisms of learning, planning, and decision-making This proposal examines the neural mechanisms supporting decision-making and prospective planning. We will examine how prefrontal cortex (PFC), hippocampus, and entorhinal cortex (EC) interact to support these processes. We will examine how non-human primates (NHPs) make choices in large decision spaces, particularly when novel choice-values have to be inferred ‘online’. We will test different models of value-coding, particularly whether PFC uses a ‘place-like’ and ‘grid-like’ code to construct cognitive maps of values spaces. We will examine how NHPs make ‘online’ choices when sequentially navigating between stimuli/states as rewards move or paths blocked. We will test whether ‘replay’ provides a neural mechanism supporting model-based planning. We will use Transcranial Ultrasound Stimulation to selectively disrupt regions of PFC/hippocampus/EC to examine its effect on neural selectivity and behaviour. These tasks are high-dimensional, yet amenable to mathematical description, and will be combined with high-density recordings to map these computations. Exp.3 will integrate our home-cage training system with wireless data-logging to record neural data continuously, across tasks and sleep, to examine how neural signatures change across days with learning, and acquisition of ‘learning set’. This provides the technology to continuously map the NHP brain during performance of diverse and naturalistic tasks, radically transforming primate neuroscience.


HLA-agnostic T-cell Targeting of Cancer

Investigator Award in Science

HLA-agnostic T-cell Targeting of Cancer Adoptive transfer of patient T-cells expressing cancer-targeting chimeric antigen receptors (CARs) has achieved remarkable success with some soluble tumours. Unfortunately, CAR-T therapy cannot treat solid tumours. Contrastingly, tumour-infiltrating lymphocyte and checkpoint inhibitor therapies demonstrate that natural T-cells can eradicate end-stage solid cancers in some patients raising interest in engineering T-cells with T-cell receptors (TCRs) for "TCR-T" therapy. Conventional anticancer TCRs recognise endogenous proteinaceous antigens as short peptides presented by human leukocyte antigen class I (HLA-I) allowing killer T-cells to scan the internal proteome and eliminate cells bearing anomalies associated with cancerous transformation. Unfortunately, even the best conventional TCR approaches are only applicable in a minority of patients due to substantial variation in HLA across the population. The ultimate TCR-T therapy would bypass HLA-restriction to enable targeting of shared cancer antigens in all individuals. Our recent discoveries that some T-cells can recognise multiple types of cancer without the need for HLA could represent a major advance for immunotherapies. I want to understand the molecular mechanisms by which such ‘HLA-agnostic’ T-cells recognise cancer and utilise these remarkable cells to identify the cell surface changes that distinguish normal from cancerous cells. These potential cancer-biomarkers and cognate TCRs could underpin novel, broad-spectrum immunotherapies.


Senior Research Fellowship Renewal

Mechanisms of reading development in deaf children
Many severely and profoundly deaf children struggle to learn to read because written text is a visual representation of spoken language, to which they have limited access. I have shown that speechreading (lipreading) relates to deaf children’s reading development.  Fully understanding the mechanisms underlying the speechreading-reading relationship is fundamental to harnessing speechreading as a tool to improve deaf children’s reading. My goal is to investigate this mechanism in 1) a longitudinal study, to determine the relationships between speechreading, phonological skills, language skills and reading over time and 2) in neuroimaging studies with deaf children and adults to investigate neural representations of visual speech and written text and the relationships between them.

All deaf participants involved in the studies above will use speechreading. A subset will also have learned British Sign Language from an early age. Good quality early sign language exposure is beneficial to reading development in profoundly deaf children. However, the mechanism underlying this relationship is unclear. I will employ parallel methods to those used in the speechreading studies to examine 1) the longitudinal relationships between sign language, fingerspelling and reading and 2) the neural representation of these visual language inputs in deaf children and adults.


Senior Research Fellowship

Long-term vascular health effects of cancer and its treatment There is increasing concern about the long-term vascular health of the large and growing population of cancer survivors. I recently showed that survivors of most types of cancer have increased risks of one or more cardiovascular diseases, beyond those explained by shared risk factors such as smoking.

The key priorities now are to understand (i) the drivers of these increased risks, and thus how and when we can most effectively intervene; and (ii) whether broader vascular-related outcomes, in particular dementia and kidney disease, are also affected.

In this fellowship I will address these two priorities by conducting analyses underpinned by cutting-edge statistical and epidemiological methods, and capitalising on rich UK and international e-Health datasets, including game-changing new cancer treatment data.

I will investigate in detail the role of anti-cancer treatments (e.g. chemotherapies/radiotherapy) and changes in traditional vascular risk factors (e.g. blood pressure, BMI) in driving late cardiovascular risk. I will then investigate whether, and through what mechanisms, cancer history affects risk of vascular dementia, chronic kidney disease, and pre-clinical cognitive and renal outcomes (uniquely identifiable in the 500,000-strong UK Biobank cohort).

Throughout, this research will contribute actionable evidence informing clinical/public health policies to improve the long-term outlook of cancer survivors.


Biomedical Vacation Scholarship Programme - University of Dundee This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs.  Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research.
Over 5 years of the Programme we encourage organisations to aim for:

-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation.

-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities.

Grants awarded from 1 October 2005 to 30 June 2021


Biomedical Vacation Scholarship Programme - University of Glasgow This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs.  Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research.
Over 5 years of the Programme we encourage organisations to aim for:

-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation.

-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities.


Biomedical Vacation Scholarship Programme - King's College London This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs.  Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research.
Over 5 years of the Programme we encourage organisations to aim for:

-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation.

-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities.