Biomedical Vacation Scholarship Programme - Queen Mary, University of 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.


How to connect an eye to a brain

Investigator Award in Science

How to connect an eye to a brain Retinal ganglion cells (RGCs) are the vertebrate eye’s only projection neurons to the brain. Through RGCs, species transmit ~50 visuo-ecologically relevant image features in parallel. However, what these features are, and how their information is used by central circuits to inform visual decisions remains unclear in any species. A key difficulty has been to link the activity of RGCs in the in vivo eye with behaviour. To address this major knowledge gap, I will capitalise on the visual system of the larval zebrafish where the activity of RGCs in the eye and their presynaptic terminals in the brain can be non-invasively monitored and manipulated in the live animal. I will ask:

 What information does the fish’s eye send to the fish’s brain?
 Does the brain "tune" its own input from the eye?
 How does the brain use information from RGCs to guide behaviour?

Taking reference of our and others’ data on RGC processing from mice and primates, we ultimately aim to arrive at a more general theory of how an eye can communicate with its brain, that encompasses coding strategies employed by diverse species with distinct visual abilities and requirements.

Key-words: Vision, projection neuron, zebrafish, 2-photon imaging

Grants awarded from 1 October 2005 to 30 June 2021

Creative Commons Attribution 4.0 International (CC BY 4.0)


Senior Research Fellowship

Circuit mechanisms that command and pattern behavioural sequences Animals accomplish goal-directed behaviours by performing sequences of motor actions. A central goal of neuroscience is to understand how neural circuits regulate behaviour in accordance with external events and internal drives and precisely choreograph diverse actions for a successful outcome. To meet this challenge, I will exploit the unique accessibility of the larval zebrafish and focus on a conserved behaviour – hunting – in which a sequence of discrete, specialised actions mediates pursuit and capture of prey. I will use a powerful experimental strategy that combines cellular-resolution calcium imaging, behavioural analyses, optogenetic circuit manipulations, neuroanatomical tracing and computational modelling to discover how brain-wide circuits operate at the cellular level to flexibly control the expression and coordination of behaviour. This paradigm will enable me to discover (1) how sensory and internal state information are integrated to control the sensorimotor decision to hunt, (2) how specific hunting actions are generated and (3) how command signals operate alongside dynamic sensory inputs to assemble a goal-directed sequential behaviour. Overall, the project will produce a mechanistic, cellular-resolution circuit model that explains how the brain controls and patterns multi-component behaviour. I expect this will reveal fundamental principles about the operational logic of the nervous system.


Targeting the gut in metabolic disease

Investigator Award in Science

Targeting the gut in metabolic disease This project aims to identify new strategies to target the gut for the treatment of type 2 diabetes and obesity.  Intestinal hormones regulate intestinal nutrient absorption, insulin secretion and appetite, and therapeutics based on the gut peptide GLP-1 are widely used for type 2 diabetes and obesity. Bariatric surgery causes weight loss and resolves diabetes at least in part via gut endocrine changes.

This project will characterise human enteroendocrine cells using intestinal organoid cultures, building on our previous work using transgenic mouse models. To identify cells of interest, organoids will be engineered by CRISPR/Cas9 to express fluorescent sensors driven by hormonal promoters, allowing cellular analysis by transcriptomics, electrophysiology and real-time fluorescence imaging of e.g. Ca2+ and cAMP. We will characterize nutrient sensing pathways and identify receptors and signaling pathways potentially modifiable therapeutically. Using mouse and human tissues, we will identify circuitry involved in bidirectional cross-talk between gut endocrine cells and enteric/autonomic nerves.

Building on our new methods to analyse peptides and the low molecular weight proteome by mass-spectrometry, we will investigate how plasma peptides respond to nutrient ingestion in health and metabolic diseases including diabetes, obesity, lipodystrophy and anorexia nervosa, and following bariatric surgery or dietary calorie restriction in obesity.


Investigator Award in Science

Investigating the phenotype, cellular interactions, and function of kidney-resident natural killer cells in health and chronic kidney disease Kidneys play a vital role in homeostasis. Chronic kidney disease (CKD) is characterised by kidney dysfunction and organ fibrosis, and affects millions of patients worldwide, but the underlying pathogenic mechanisms are poorly understood.  Using single cell RNA sequencing, we have shown that the human kidney contains a network of tissue-resident immune cells, including macrophages and two subsets of natural killer (NK) cells. These NK subsets have distinct transcriptional signatures suggestive of differing interactions with macrophage subsets, and the potential to variably influence tissue repair/fibrosis by via production of the epidermal growth factor receptor ligand amphiregulin (AREG) and by regulating macrophage polarisation towards a wound-healing M2 phenotype.

My key goals are:
1. To determine the functional characteristics, cellular interactions, developmental relationships and lifespan of NK cell subsets in normal human kidney.
2. To understand how the global kidney immune landscape and NK cell phenotype/function/interactions change in CKD.
3. To determine if NK-cell depletion or NK cell-specific AREG-deficiency affects macrophage polarisation and kidney fibrosis in mouse models of kidney injury.
Answering these questions will provide critical information about tissue immunity in the kidney, delineate previously unappreciated aspects of NK cell biology, and will potentially identify new therapeutic targets for CKD.


Investigator Award in Science

Cellular dissection of Plasmodium falciparum erythrocyte invasion Plasmodium falciparum parasites still cause nearly half a million deaths each year. The repeated emergence of antimalarial drug resistance and the lack of a highly effective vaccine mean that there is an urgent need to identify new intervention targets. Erythrocyte invasion is an excellent target as it is essential for both parasite survival and for malaria pathology. Invasion involves multiple parasite ligands, but little is known about their function at the cellular level and even less about how they fit into the broader network of invasion proteins. This proposal will revolutionise our understanding of the function of two families of P. falciparum invasion ligands, the EBLs and the RHs, that are together responsible for the key decision point in the invasion process. The key goals are to:

 Systematically dissect functional equivalence between EBLs and RHs
 Establish the roles that EBLs and RHs play in discriminating between erythrocyte variants within and between humans
 Use innovative combinatorial approaches to move from a gene to a network understanding of EBL and RH function.

The proposal will provide a step change for the field, both biologically and technically, and will identify new candidates for testing in a rationally designed, multi-component invasion-blocking vaccine.


Investigator Award in Science

Towards a thorough mechanistic understanding of endosomal cargo sorting. An intracellular nexus for regulating the membrane trafficking of many of the 5,000+ integral proteins encoded by the human genome is the endosomal network.  Composed of vesicular and tubular early and late endosomes, the network’s principal role is to sort integral proteins (termed ‘cargoes’) arriving from the cell surface and the biosynthetic pathway between two fates: either sorting to the lysosome for degradation, or retrieval from this fate for export to the cell surface, the biosynthetic pathway or other specialised organelles.  Whilst the molecular details of degradative cargo sorting have been well documented, those events that conduct cargo retrieval and export remain poorly understood. Our research has sought to fill this fundamental void in metazoan cell biology.

A master conductor of endosomal retrieval and export is the retromer pathway - in human cells this orchestrates the sorting of  > 900 cargoes.  Establishing how this pathway functions is central to understanding the evolution, organisation and activity of endosomal sorting.  With Wellcome support we will address two integrated questions:

 The fundamental question of how the retromer pathway is organised and integrated with other pathways to orchestrate global endosomal cargo sorting.
 How understanding of retromer pathway function may provide vital insight into neurodegenerative diseases.


Investigator Award in Science

Bridging the gap: biophysical models of human frontotemporal lobar degeneration
To treat and prevent dementia in patients, it is essential to understand how microscopic changes in the human brain cause complex cognitive and behavioural disorders. My program addresses this critical gap in translational research, to facilitate clinical application of basic science discoveries. I have three goals, set in the context of frontotemproal dementia and progressive supranuclear palsy.

First, I will develop quantitative biophysical models of human brain function that capture key cellular and pharmacological pathologies in vivo, with regional, laminar and synaptic specificity. These models of degenerating neuronal circuits are informed by individual measures of synaptic density (PET imaging with a SV2a ligand), GABA and glutamate (ultrahigh-field MR spectroscopy). They are optimised in vivo by inversion to magnetoencephalography, and tested post-mortem against neuropathology.  This synergy of multi-modal imaging, together with Bayesian model comparison of Dynamic Casual Models, means one can drill down to the best mechanistic model of the human cognitive disorder.

Second, I will show how harmful effects of dementia like apathy can be explained in terms of changes in synaptic density and loss of precision in hierarchical brain networks.

Third, I will I demonstrate the readiness of my approach for experimental medicine, through longitudinal designs and pharmacological interventions.


Investigator Award in Science

Exploring mitochondrial metabolism in health and disease using targeted biological chemistry The molecular mechanisms by which mitochondrial reactive species, metabolites and redox signals contribute to physiology and pathology are unclear. This is in large part because these processes are difficult to assess and modulate in vivo. Our goals are to establish general chemical biology approaches to determine the mechanisms of mitochondrial physiology and dysfunction in vivo and from this develop new therapeutic strategies. The aims are based on the success of our previous Joint Investigator Award, but the specific chemical biology approaches to be used, the insights to be attained and the models have been refined and developed, based on our work over the past four years. These goals will be achieved by addressing three research challenges in cells and in vivo:

A: Can we determine how mitochondria operate during normal physiology, and are disrupted during pathology, by targeting probes to measure reactive species and alterations to signaling pathways?

B: Can targeting bioactive molecules to mitochondria prevent pathological disruption of mitochondrial function and generate potential therapies?

C: Can the above methods to monitor and modulate mitochondrial function be assessed in animal models of human diseases and thus drive the development of rational, translatable therapies?


Investigator Award in Science


Investigator Award in Science

Neuro-immune-stromal pathways sense environmental change to regulate repair versus remodelling during airway disease This application will test the hypothesis that pulmonary immune homeostasis is maintained by a network of tissue resident cells that continually monitor environmental change. Disruption of local neuro-immune-stromal interactions either by genetic or environmental factors, alters the threshold for immune responses to usually innocuous particles such as dust, pollen or dander leading to chronic airway inflammation and tissue remodelling. I will ascertain the cellular and molecular composition of the airway wall parenchyma in children and adults with severe asthma and use machine learning tools and mouse models to determine the impact on lung function. Viral infection and pollution are common triggers for asthma severity, and I will establish how the immune/stromal niche communicates with the external environment to react to these inhaled stimuli, focussing on interaction with neuronal systems. I will examine how these interactions differ in severe asthma and contribute to the ensuing inflammation, remodelling and lung dysfunction. I will investigate the cellular interactions between fibroblasts, extracellular matrix and type 2 immune cells that facilitate repair versus remodelling during severe asthma. Ultimately this programme will reveal insight into mechanisms underlying tissue remodelling versus repair during severe asthma.


Investigator Award in Science

Secretory protein folding, modification and the unfolded protein response Proteins entering the secretory pathway at the endoplasmic reticulum (ER) undergo a vast array of post-translational modifications some of which are essential for correct folding, assembly and secretion.  Failure to fulfil these functions results in several diseases due to the lack of secretion of proteins such as insulin and antibodies, or due to cell death triggered by an unfolded protein stress response.  The ER provides a unique environment for protein modifications such as disulfide formation and glycosylation.  To ensure efficient protein folding and secretion the cell maintains the environment within the ER that ensures these processes occur efficiently and reacts to situations of cell stress.  This proposal builds on exciting new observations from my group to dissect molecular mechanisms involved in secretory protein biogenesis.  Our particular focus will be on how the cell maintains ER redox balance, how the repertoire of ER folding factors orchestrate correct protein folding and N-linked glycosylation and how the UPR sensor ATF6 is activated following proteotoxic stress.  Our aims will be achieved using a combination of innovative new technological approaches and previously established robust assays to follow protein folding and assembly in both reconstituted and cellular systems.


Biomedical Vacation Scholarship Programme - HDR-UK 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 - University of Bristol 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.


Investigator Award in Science

The Molecular Basis of Sister Chromatid Cohesion Cohesion between sister chromatids, mediated by the chromosomal cohesin complex, is a prerequisite for faithful chromosome segregation during cell division. The ring-shaped cohesin complex is a multisubunit ATPase that topologically loads onto DNA in the G1 phase of the cell cycle. The first part of the proposal will elucidate the molecular mechanism of cohesin function. We will employ and develop biophysical, structural and DNA-protein crosslink mass spectrometry tools to map the trajectory by which DNA enters the cohesin ring, fuelled by ATP-dependent conformational changes. The second part of the proposal examines the establishment of sister chromatid cohesion during S phase. We will investigate how, as the replication fork moves along DNA, cohesin transitions from containing one DNA to embracing two newly replicated DNAs. This includes the functional characterisation of replisome components with roles in sister chromatid cohesion, known as ‘cohesion establishment factors’. Furthermore, we will take advantage of recent success with the biochemical reconstitution of complete DNA replication and work towards recapitulating sister chromatid cohesion establishment in vitro. This will open unique experimental opportunities to understand the process. Together, this programme will provide insight into the molecular mechanism of how cohesin safeguards faithful chromosome segregation.


Collaborative Award in Science

Dr Dylan Childs, Prof Craig Winstanley, Prof Steve Paterson, Prof James Chalmers

Understanding and predicting the evolution of antibiotic resistance in human infection The evolution of antibiotic resistance is a threat to modern medicine. Patients with chronic bacterial infections are at particular risk from antibiotic resistant genotypes, which typically arise from within the infection. However, a lack of controlled studies means that we don't understand how antibiotic resistance evolves within the human host environment, and why the emergence of resistance varies among patients.

We identify randomised clinical trials (RCTs) of new antibiotic treatments as a powerful way to study resistance evolution in action during a controlled, replicated natural experiment. We will exploit a unique opportunity to perform an evolutionary analysis of two parallel Phase-III RCTs for inhaled ciprofloxacin treatment of chronic lung infections caused by Pseudomonas aeruginosa, which is a WHO Priority-1 pathogen in critical need of improved antibiotic therapies. Ciprofloxacin resistance emerged in ~40% of the treated patient infections but this patient-to-patient variation is unexplained.

We aim to explain why resistance evolved in some patients but not in others. To do this, we will (1) discover the evolutionary mechanisms of resistance emergence in patient infections, (2) identify the bacterial and host properties that drove resistance evolution, and then (3) test how well biomarkers of these drivers predict resistance emergence in other patients.


Biomedical Vacation Scholarship Programme - University of Leicester 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 - University of Nottingham 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 - University of Cambridge 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 Oxford 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 - University of Manchester 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 - University of Edinburgh 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 - University 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.


Biomedical Vacation Scholarship Programme - University of Sheffield 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 - University of East Anglia 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.


Senior Research Fellowship

Micronutrient interventions to improve infant neurocognitive development and growth in early infancy Undernutrition during the early years of life has a harmful and irreversible impact on child growth and cognitive development. Many of the interventions tested to improve outcomes across infancy have had disappointing or inconsistent impact, a common feature being the absence of any attempts to provide nutritional supplements to infants during the first six months. With increasing evidence of micronutrient deficiencies in this age group, alongside strong evidence that growth and developmental deficits begin before six months, a renewed focus on the micronutrient status of infants is required.

Here I propose a randomised efficacy trial of micronutrient supplementation to mothers (during pregnancy or pregnancy and lactation) and infants (birth to six months) in rural Gambia, where rates of micronutrient deficiencies are high. 600 pregnant women (

This novel research will identify the most efficacious way of improving micronutrient status in infancy, and assess impact on infant developmental outcomes, providing an evidence base for future effectiveness trials and policy recommendations.

Infant Nutritional Physiological Phenomena

Maternal Nutritional Physiological Phenomena


Investigator Award in Science

Discovering new pathways of lymphocyte specification and function The co-ordinated development and differentiation of lymphocytes is critical to producing the bespoke immune responses required to combat specific pathogens, but also to maintaining tissue homeostasis and repair.  However, dysregulated immune reactions underlie undesirable chronic inflammation and autoimmunity.   Our discovery of type-2 innate lymphoid cells (ILC2) and the description of other ILC subsets has highlighted additional, previously unappreciated, complexity in the processes of lymphocyte specialisation.  Our challenge is to unravel the microenvironmental cues, critical cell-surface receptors, and key transcription factor interactions that lead to lymphocyte specification, tissue-specific roles and cellular interactions. We will employ a unique repertoire of lymphocyte transcription factor reporter "polychromILC" mice in combination with CRISPR-mediated screens to identify new regulators of lymphocyte development, differentiation and function.  To facilitate the investigation of these new pathways in specific lymphocyte subsets in vivo we will produce a new generation of mouse strains designed to limit off-target events by employing multiple positive and negative determinants, comparable to Boolean operators (AND, OR, NOT or AND NOT).  Finally, using a combination of genetic screens and in toto adaptive light-sheet microscopy we aim to define molecules and cells that delineate the migration and development of ILC in the context of the stromal environment.


Senior Research Fellowship

Imaging the Redox Microenvironment to Predict Tumour Resistance to Therapy The majority of lung cancer deaths result from ineffective treatment of late-stage disease. Currently, there is no satisfactory way to identify patients that will not respond to standard-of-care treatments. Positron emission tomography (PET) imaging offers a potential solution to this clinical problem through the non-invasive assessment of molecular processes that underpin therapy-resistance. The identification of cancer patients that are refractory to treatment will allow the selection of second-line therapies that have the potential to improve patient response and survival.

For this SRF, I will develop novel PET radiotracers to predict therapy resistance in mouse models of non-small cell lung cancer. These radiotracers will non-invasively image the aberrant activity of key antioxidant pathways that are causal to therapy resistance. Specifically, I will use structure-activity relationships and in vivo imaging to design highly-specific radiotracers for the cancer stem cell marker, aldehyde dehydrogenase 1A1; nuclear factor erythroid 2-related factor 2, the master regulator of the antioxidant response; and de novo glutathione synthesis. Our library of redox radiotracers will subsequently be used to detect drug resistance in syngeneic, isogenic and patient-derived models of lung cancer. Finally, I will use the radiotracers developed in this programme to assess response to immunotherapy in drug-resistant lung cancer.


Senior Research Fellowship

Factors Determining Clonal Selection in Germinal Centres Antibody affinity maturation occurs in germinal centers (GCs) through iterative rounds of somatic hypermutation (SHM) in dark zones (DZs) and selection in light zones (LZs). Current models state that, following SHM, DZ cells exit cell cycle and move to LZs to test their newly mutated B cell receptors by competing T cell help. High affinity B cells preferentially "win" in receiving help, and this causes them to undergo cyclic reentry (defined by S phase initiation and DZ re-entry). We recently demonstrated the possible existence of a second checkpoint, because BCR expression is required for LZ entry. We propose testing the nature of BCR-dependent signals required for this (e.g. cognate vs tonic signaling). Next, we will re-examine the fundamental principle that affinity enhancements are favored by LZ cells competing for cyclic re-entry promoting cues. In unpublished studies, we unexpectedly find that T cell help in not required for initiating cyclic re-entry. We will therefore test whether LZ cells compete for other non-T cell-derived cues, or whether instead cyclic re-entry is controlled independently of selection events. Finally, we will investigate whether GCs utilize innate cell types and signaling pathways for sensing the continued presence of foreign material and for determining GC longevity.


lvermectin Safety in Small Children

Innovations Priority Project

lvermectin Safety in Small Children lvermectin is a very safe and beneficial drug which is used for the treatment of more than a
dozen different neglected tropical diseases (NTDs), many of which are associated with
important public health problems. Current label indications for ivermectin prevent use in
small children weighing less than 15kg, due to limited safety data in this group. Many of the
NTD treatment options for small children rely on compounds that are less safe and/or
efficacious compared to oral ivermectin. Our proposal will establish the safety and
pharmacokinetics of escalating doses of ivermectin to treat scabies infected children weighing less than 15kg. The safety assessment will provide crucial evidence on the use of
ivermectin for numerous diseases in children weighing less than 15kg. The information from
measuring drug concentrations in the patients will inform the optimal dosing of this drug in
small children. Assessment of the efficacy of ivermectin, compared to permethrin cream, for
the treatment of scabies in small children can provide an important alternative treatment for
this widespread disease.


DFID-Wellcome Epidemic Preparedness Grant

Unprecedented Movement to drive a Unified Rwandan Initiative for National ZEBOVAC Immunization The ongoing outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of Congo (DRC) and the recent identification of Ebola cases in the cities of Goma and Bukavu (which border Rwanda) are of particular concern and have prompted the Rwandan Government to take control measures for preventing cross-border spread of EVD. As demonstrated by the current outbreak, purely reactive measures may be insufficient to fight Ebola. Prophylactic approaches are needed that can prevent emergence of EVD in previously unaffected areas.We propose to conduct a large scale vaccination campaign targeting 196,000 individuals living and working in border-proximate areas; a clinical trial to evaluate the immunogenicity of the AD26.ZEBOV, MVA-BN-Filo vaccine in 2,000 people; and a clinical trial to evaluate the safety of the vaccine among 2,000 pregnant women in the context of this new framework of Ebola prevention. These 3 programs will together generate a large cohort that can be revisited for a long term follow up study to assess long term immunogenicity at different times following vaccination; an evaluation of a potential effect of booster doses and the optimal strategy for booster administration; and an evaluation of long term assessment of effectiveness using a test-negative case control study design.


Unprecedented Movement to drive a Unified Rwandan Initiative for National ZEBOVAC Immunization The ongoing outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of Congo (DRC) and the recent identification of Ebola cases in the cities of Goma and Bukavu (which border Rwanda) are of particular concern and have prompted the Rwandan Government to take control measures for preventing cross-border spread of EVD. As demonstrated by the current outbreak, purely reactive measures may be insufficient to fight Ebola. Prophylactic approaches are needed that can prevent emergence of EVD in previously unaffected areas. We propose to conduct a large-scale vaccination campaign targeting 196,000 individuals living and working in border-proximate areas; a clinical trial to evaluate the immunogenicity of the AD26.ZEBOV, MVA-BN-Filo vaccine in 2,000 people; and a clinical trial to evaluate the safety of the vaccine among 2,000 pregnant women in the context of this new framework of Ebola prevention. These 3 programs will together generate a large cohort that can be revisited for a long term follow up study to assess long term immunogenicity at different times following vaccination; an evaluation of a potential effect of booster doses and the optimal strategy for booster administration; and an evaluation of long term assessment of effectiveness using a test-negative case control study design.


Sir Henry Dale Fellowship

Royal Society/Wellcome Trust Sir Henry Dale Fellowship

Sir Henry Dale Fellowship Interview Committee

Mechanisms of spliceosome remodeling and splice site selection during the catalytic stage of mammalian pre-mRNA splicing The spliceosome produces mRNAs in two sequential transesterifications – branching and exon ligation. The post-branching C complex is remodeled by the ATPase Prp16 into the C* complex. Prp16 allows binding of the exon ligation factors Cactin and FAM32A, which stabilise docking of the 3’-splice site (3’SS) at the active site. While in yeast Prp18 is constitutively bound to C* spliceosomes, in humans Prp18 and other exon ligation factors of unknown function appear to engage the C* spliceosome in a transcript-specific manner. Here, I will reconstitute the C to C* transition in vitro in mammals and use biochemistry and cryo-electron microscopy to isolate and visualize novel intermediates and dissect the structural mechanisms by which Cactin, FAM32A, Prp18, and additional exon ligation factors cooperate to promote Prp16-mediated remodeling and to ensure correct 3’SS choice. In parallel, iCLIP studies will reveal where these exon ligation factors bind across all human pre-mRNAs and how RNA sequences around the splice sites determine the association of subsets of factors on specific pre-mRNAs. This work will elucidate how Prp16 drives remodeling of the human catalytic spliceosome and will investigate whether exon ligation factors regulate alternative splicing in a sequence-specific manner while proofreading 3'SS recognition during exon ligation.


Africa and Asia Programmes

Prof Elizabeth Ashley, Prof Frank Smithuis, Dr Direk Limmathurotsakul, Prof Phaik Yeong Cheah, Prof Arjen Dondorp, Prof Francois Nosten, Prof Mallika Imwong, Prof Sir Nicholas White, Prof Guy Thwaites, Prof Kesinee Chotivanich, Prof Paul Turner

Thailand Africa and Asia Programme - GBP Core The Wellcome Thailand AAP has conducted high quality impactful research for 40 years on infectious diseases of major public health concern, leading to the widespread adoption of new approaches and treatments for many of them including malaria, melioidosis, and rickettsial infections. In our fifth decade we will focus on ensuring sustainable impact and influence on policymakers by strengthening our research network and developing the capabilities of our partner institutions. Our vision is to:

1. Through research continue to address public health problems with regional and global relevance, using cutting edge approaches to seek affordable and deployable solutions to disease prevention, diagnosis and patient management.

2. Maximise our public health research’s uptake and impact, incorporating health economics analysis and goal-driven engagement with policymakers, national academic institutions, hospitals, industry partners, communities and the general public.

3. Work with our local host institutions to increase their national and global impact by integrating activities including training programmes, joint research projects, and supporting partner-led programmes to translate research into policy and practice.

Our goal is to improve life quality and expectancy by reducing the adverse impact of infectious diseases, which account for much of the disparity in health metrics between low and high income countries.


Africa and Asia Programmes

Dr Direk Limmathurotsakul, Prof Arjen Dondorp, Prof Francois Nosten, Prof Guy Thwaites, Prof Kesinee Chotivanich, Prof Paul Turner, Prof Frank Smithuis, Prof Sir Nicholas White, Prof Elizabeth Ashley, Prof Mallika Imwong, Prof Phaik Yeong Cheah

Thailand Africa and Asia Programme THB Core Award The Wellcome Thailand AAP has conducted high quality impactful research for 40 years on infectious diseases of major public health concern, leading to the widespread adoption of new approaches and treatments for many of them including malaria, melioidosis, and rickettsial infections. In our fifth decade we will focus on ensuring sustainable impact and influence on policymakers by strengthening our research network and developing the capabilities of our partner institutions. Our vision is to:

1. Through research continue to address public health problems with regional and global relevance, using cutting edge approaches to seek affordable and deployable solutions to disease prevention, diagnosis and patient management.

2. Maximise our public health research’s uptake and impact, incorporating health economics analysis and goal-driven engagement with policymakers, national academic institutions, hospitals, industry partners, communities and the general public.

3. Work with our local host institutions to increase their national and global impact by integrating activities including training programmes, joint research projects, and supporting partner-led programmes to translate research into policy and practice.

Our goal is to improve life quality and expectancy by reducing the adverse impact of infectious diseases, which account for much of the disparity in health metrics between low and high income countries.


Africa and Asia Programmes

Prof Frank Smithuis, Dr Direk Limmathurotsakul, Prof Francois Nosten, Prof Guy Thwaites, Prof Phaik Yeong Cheah, Prof Arjen Dondorp, Prof Elizabeth Ashley, Prof Mallika Imwong, Prof Sir Nicholas White, Prof Kesinee Chotivanich, Prof Paul Turner

Thailand Africa and Asia Programme - PPE Award The Wellcome Thailand AAP has conducted high quality impactful research for 40 years on infectious diseases of major public health concern, leading to the widespread adoption of new approaches and treatments for many of them including malaria, melioidosis, and rickettsial infections. In our fifth decade we will focus on ensuring sustainable impact and influence on policymakers by strengthening our research network and developing the capabilities of our partner institutions. Our vision is to:

1. Through research continue to address public health problems with regional and global relevance, using cutting edge approaches to seek affordable and deployable solutions to disease prevention, diagnosis and patient management.

2. Maximise our public health research’s uptake and impact, incorporating health economics analysis and goal-driven engagement with policymakers, national academic institutions, hospitals, industry partners, communities and the general public.

3. Work with our local host institutions to increase their national and global impact by integrating activities including training programmes, joint research projects, and supporting partner-led programmes to translate research into policy and practice.

Our goal is to improve life quality and expectancy by reducing the adverse impact of infectious diseases, which account for much of the disparity in health metrics between low and high income countries.

Grants awarded from 1 October 2005 to 30 June 2021


Investigator Award in Science

How cell migration and differentiation are coordinated during morphogenesis During development the embryo needs to generate functional organs composed of many different cell types, often originated in different embryonic location.  Thus, it is clear that cell differentiation and migration need to be tightly coordinated, although they are often studied as independent processes. Here I will test the hypothesis that cell migration and differentiations are coordinated by tissue mechanics in vivo. Specifically, I will challenge the current view that cell migration is the result of differentiation, by testing instead whether the reverse occurs, i.e. migration controls differentiation. I will use neural crest cell, a multipotent embryonic cell population in which cell differentiation is always linked to cell migration.

One of the problems to study biomechanics in vivo is the limited number of tools to measure and modify mechanical properties in vivo. Here I will develop new tools to analyse and change tissue stiffness in vivo. We will analyse how these mechanical changes influence cell migration and differentiation, and we will identify the molecular response elicited in the neural crest cells. We expect that this multidisciplinary project will provide answers to a central yet unresolved question in developmental biology: how cell fate and migration are integrated during embryo development.


Discretionary Award – C&S

Politics, elections, and inclusive decision-making: Do political institutions affect health? Do political institutions influence the health of populations? Political institutions once seemed fixed and stable, but now appear to be flexible and open to change. This project seeks to uncover whether changing political institutions could affect health. Political institutions are the rules that govern who participates and how they participate in decision-making processes within societies; for example, they dictate who gets to vote and how votes are counted. Political institutions potentially affect health because they make governments more (less) responsive to what citizens want. However, this straightforward view of how political institutions affect health overlooks how democracies can privilege some voices over others (e.g., party donors may matter more than voters) and so universal suffrage may not necessarily deliver better health. This project will shed light on these questions through a series of empirical case studies. For example, I propose to examine whether political incorporation improves the health of formerly excluded groups, and whether their influence on policy decisions is weaker in majoritarian political systems than proportional representation systems because votes are counted differently. This project speaks to the sustainable development agenda by illuminating whether inclusive and representative decision-making institutions may accelerate progress toward ensuring healthy lives for all.


Sir Henry Dale Fellowship

Highly sensitive brain blood flow measurements using ultra-high field magnetic resonance imaging Blood flow is critical for maintaining the steady supply of oxygen and nutrients to the brain, and blood flow changes are present in a range of diseases including stroke and dementia. Conventional methods for in vivo blood flow mapping have limitations and often cannot be used for longitudinal monitoring or research.

In this proposal I aim to develop highly sensitive imaging methods for measuring brain blood flow based on a non-invasive magnetic resonance imaging technique, arterial spin labelling, applied at ultra-high field. The main goals of this research are:

 To establish a robust platform for ultra-high field arterial spin labelling by developing novel approaches to overcome a range of technical challenges associated with this technique;
 To develop advanced imaging approaches which allow richer cerebrovascular information to be obtained, including high resolution angiography and vessel-selective imaging;
 To demonstrate the high sensitivity achievable with these novel methods by measuring changes in white matter perfusion in patients with vascular cognitive impairment, and probing the brain’s response to tonic pain at unprecedented spatial resolution.

These new methods will be actively shared with local, national and international collaborators, enabling previously unfeasible clinical and basic science research studies to be performed.


Sir Henry Dale Fellowship

Stress signalling in intestinal maintenance and regeneration Many adult epithelial tissues lose cells from constant environmental stress. Thus, an epithelium’s ability to sense stress, defend itself and stimulate repair (e.g. by stem cells) is vital to prevent tissue dysfunction, degeneration, inflammation and cancer.

Despite its importance, this process is poorly understood. Using the adult Drosophila intestine and its unparalleled genetics, combined with proteomics, transcriptomics and fixed and live imaging, I will determine how stress signalling promotes epithelial resilience, maintenance and regeneration focussing on three main aims.

1) Reactive oxygen species (ROS) produced by damaged fly intestinal epithelial cells (IECs) promote intestinal stem cell (ISC)-mediated regeneration, partly via p38 signalling in IECs. I will determine how ROS promote intestinal regeneration by identifying ROS-controlled regulators of regeneration and determining molecular responses to ROS/stress signalling.

2) I have recently found that some stress pathways display rhythmic, circadian activation. I will investigate their role in intestinal maintenance.

3) I have shown that when new IEC production by ISCs is inhibited, IECs increase their lifespan to prolong epithelial maintenance. I will identify adaptive mechanisms that extend IEC lifespan when new cell production is blocked.

Understanding these processes could provide novel therapeutic strategies for tissue regeneration, inflammatory diseases, cancer and age-related pathologies.


Sir Henry Dale Fellowship

RNA helicases as regulators of the response of B-cells to programmed DNA rearrangements In mature B-cells, the generation of antibodies of different isotypes relies on class switch recombination (CSR) mechanisms. Although crucial for adaptive immunity, CSR imposes challenges to genome integrity as it involves programmed induction of DNA double-strand breaks (DSBs) in rapidly proliferating B-cells. A key player in the cellular response to CSR DSBs is the protein kinase ataxia telangiectasia mutated (ATM). Evidence suggests RNA-dependent mechanisms control the DNA damage response by ATM, although there is very limited understanding of how these function in B-cells and which RNA-binding proteins (RBPs) are required for CSR. This proposal aims to define the critical roles of RNA helicases as integrators of ATM signals to control class switch recombination mechanisms in B-cells. I propose an integrative approach combining genomic and proteomic methodologies together with ex vivo B-cell differentiation systems and conditional gene-targeting in mice. I will determine RNA helicase-dependent mechanisms controlling the cell-cycle and CSR DSB-repair and investigate their roles in B-cell immune responses. This work will provide new insight into RNA helicase-mediated pathological mechanisms resulting in CSR deregulation and the development of immune disease or B-cell lymphomagenesis.


Sir Henry Dale Fellowship

Molecular mechanisms of slow axonal transport
Neuronal axons can be a metre long and are maintained for a lifetime, making them acutely vulnerable to defects in microtubule mediated long distance transport. There are two broad categories of axonal transport in neurons, fast and slow. Slow axonal transport carries at least three times the material of fast transport, but ten to a hundred times more slowly. Protein moved by slow transport can be months old in the distal axon, and this process slows further with aging. Despite dysfunctional axonal transport being common in neurodegeneration, where aging is the major risk factor for disease, the mechanisms that regulate slow transport are very poorly characterised. Critically, whether transport time directly affects the accumulated damage and function of its protein cargo is unknown. The aim of this project is to understand how slow transport is regulated, whether transit time can influence the half-life and function of proteins, and further - whether it’s possible to reverse age-related decline in transport. To do this I will employ a multidisciplinary approach through the application of single-molecule light microscopy techniques. This project will define the relationship between the machinery of transport and the life cycle of axonal proteins.


Sir Henry Dale Fellowship

Manipulating wound inflammation and angiogenesis to rescue defective tissue repair Compromised wounds are increasingly prevalent, affecting quality of life for millions of sufferers and incurring a substantial burden on the NHS. I will define how macrophages control angiogenesis to drive wound healing and how this process breaks down to result in compromised wounds, particularly in the context of diabetes, using zebrafish and human co-culture models. Using RNAseq, I will profile zebrafish macrophages and endothelial cells in response to wounding, identifying the critical signals driving angiogenesis and how these fail in diabetic mutants. I will visually verify the roles of these key signalling genes by generating zebrafish transgenic reporters to live-image their wound response. In combination with novel CRISPR gene editing tools, I will establish specific manipulations to clinically relevant candidates, defining their functions and developing models of compromised wounds. The macrophage-HUVEC co-culture model will complement these zebrafish studies, corroborating the functions of macrophages from healthy versus diabetic patients. Expanding on this assay, I will use siRNA knock-down in monocyte-derived macrophages to dissect the role of clinically relevant candidates in perturbing macrophage control of angiogenesis. Together, these fish and human tissue culture models will provide a platform to identify novel therapeutics and propel the translation of these treatments towards the clinic.


Sir Henry Dale Fellowship

Identification of genomic components that predict transmission of the malaria parasite in different vector species The malaria parasite (Plasmodium falciparum) has a complex life cycle in which it must transit through multiple environments in a vertebrate host and mosquito vector. Transmission begins with ingestion of an infectious blood meal by one of 40 potential Anopheles mosquito species capable of transmitting the disease. This initiates the most extreme population bottleneck in the life cycle in which the parasite must rapidly undergo fertilisation, develop into an invasive form and transit through the midgut epithelium. The overarching goal of this proposal is to understand how this transmission through the mosquito vector drives selection on the parasite. I hypothesise that parasites have adapted to their local vector community composition, and this shapes their ability to infect sympatric and allopatric vector species. Using large-scale transmissibility assays and single-cell RNA-sequencing, I will identify genomic and transcriptomic vector-dependent signatures of transmission. I will then generate allelic-replacement parasites to unambiguously attribute phenotypic variation in species-specific transmission to specific loci in the parasite. Comprehensively understanding how vector communities shape parasite populations will guide future interventions and vector control programs by providing information that will allow for strategies to be locally tailored based on parasite genomic-surveillance and entomological surveys.


Sir Henry Dale Fellowship

Mechanisms and roles of transmissible RNA Protein coding and non-coding RNA can spread between cells and tissues of an organism. RNA mobility between organisms has been documented within and among different kingdoms of life including fungi, plants and animals. However, the underlying mechanisms and roles of such transmissible RNA are poorly understood. Our recent studies demonstrated that honeybees share biologically active RNA among members of the hive through secretion and ingestion of worker and royal jellies. The jellies harbor naturally occurring exogenous (e.g. viral) and endogenous RNA. These findings suggest that RNA transfer plays a role in social immunity and signaling between honeybees. Therefore, the key goals of this proposal are: to establish a metabolic RNA labeling system in honeybees; and to apply this system to study natural RNA transfer-mediated antiviral immunity and impacts on the physiology of recipient bees. To achieve these goals, I will combine RNA biology techniques and imaging with high-throughput sequencing to establish a functional transmissible RNA pathway in honeybees. This project will provide knowledge and tools that will enable studying the biology of RNA flow in other organisms, including humans, in diverse biological aspects; hence, will ultimately contribute to the development of RNA-based applications to promote health and disease control.


Sir Henry Dale Fellowship

Understanding the impact of global change on animal-borne diseases We know little about how future climate change, habitat destruction, human population increases and greater globalisation processes will impact human zoonotic diseases. Here, I investigate the use of dynamic, seasonal host population models to better predict the impact of real-time environmental change on disease-carrying host species, within a general systems-dynamics, disease framework. Specifically, I will combine a mathematical compartmental disease model with a host population ecology model, within a spatial and temporal Bayesian framework.  Using this approach, I will first model Lassa Fever using climate and land-use observations, collaborating with the Nigerian government. I will then augment my model to account for animal movement patterns and vector species abundances, to examine arboviral disease spread in North America. Then, I will integrate these threads into a general, dynamic modelling framework for zoonotic diseases, which will contain both the newly developed components and my previously developed model of human movement and behaviour. Working with the World Health Organisation, I will create short- and long-term disease forecasts for a set of high priority zoonoses. Once validated against human case data, these mechanistic models can be used to test interventions and create future disease management plans that are robust to upcoming global change.


Sir Henry Dale Fellowship

Analyses of paired host-virus genomic data to understand disease heterogeneity of chronic viral infections. Host and pathogen genetic variations are major causes of clinical outcomes of infectious diseases. Traditionally, genetic studies of infectious diseases have sought to explain between-individual variation in disease by assessing genetic factors separately in humans or pathogens, under the assumption that these factors are independent. However, there is strong theoretical evidence that genetic interactions between host and viruses play a major role in viral disease aetiology. The major limiting factor to date has been the lack of cohorts with paired host-virus data. Recent technological developments and reductions in the cost of high-throughput viral sequencing from clinical samples have provided new opportunities to analyse host-virus genomic data generated from the same patients. In this project I propose to analyse paired host-virus genomic data from patient cohorts infected with HBV, HCV and HIV (clinically the most important chronic viruses worldwide) to answer the following questions:

1) What are the host genetic pressures driving virus evolution across different host populations and virus lineages?

2) What host and virus genetic interactions drive disease phenotypes?

3) What are the host genetic variants and pathways linked to disease phenotype across the three chronic viral infections of HBV, HCV and HIV?


Sir Henry Dale Fellowship

Purpose and Mechanisms of Behavioural Modulation in Retina and Superior Colliculus The project aims to uncover why and how behavioural states like arousal affect neural processing in the early visual system by recording from the retina and superior colliculus in awake mice using techniques I have previously developed. Behavioural states affect task performance but their effect on early sensation is unclear; understanding their impact on early visual processing will reveal fundamental computational principles of adaptation.

Our objectives are:

 determine the effects of behavioural states on different cell types in the early visual system by recording activity of retinal and collicular neurons classified by function, genetics and projection targets in awake mice.
 determine the purpose of behavioural state modulation in terms of information processing in the early visual system by recording activity of retinal and collicular cell types in awake mice viewing visual stimuli that elicit nonlinear responses or are behaviourally relevant.
 determine the mechanisms by which behavioural states influence early visual processing by measuring and manipulating the activity of neuromodulators, serotonin and noradrenaline, controlling behavioural states while recording from retinal and collicular neurons.

The results of this project impact on basic neurosciences and other fields including the development of artificial intelligent systems and the treatment and diagnosis of psychiatric disorders.


Action in Vision

Sir Henry Dale Fellowship

Action in Vision How do vision and motor actions interact? A textbook will answer that vision guides movements but this view has been challenged over the last decade. The most striking realisation was the extent to which locomotion modulates neural activity in primary visual cortex, thalamus dLGN, superior colliculus and even the retina (collectively Early Visual System or EVS). Therefore movements can guide visual processing but the nature of this effect is unknown.

The most pressing question regards the specificity of these interactions. In EVS different visual features (size, luminance, colour, direction ...) are processed along parallel channels, at least 30 in the mouse retina. Since different motor actions (e.g. picking a fine thread, kicking a ball) require different visual features, I expect the interactions between vision and movements to be quite specific to the nature of the actions performed.

Due to technological limitations the only available data are obtained in head-fixed animals where only one type of action – locomotion – can be observed. To overcome these limitations I developed a system to quantify movements in unconstrained animals.  I will use this system to understand how different movements affect distinct visual channels in EVS, modify the neural code(s) and ultimately influence behaviour.


Innovations Priority Project

Prof Julia Schnabel, Dr Bernhard Kainz, Prof Daniel Rueckert, Prof Reza Razavi

A computer-guided imaging system for prenatal screening and comprehensive diagnosis of fetal abnormalities In the UK and in many countries around the world, it is routine for women to undergo an
ultrasound (US) screening examination about halfway through pregnancy to check if their
fetus is developing normally. This is important as undiscovered fetal anomalies can have a
lifelong impact on the families affected, with huge cost to health services as well as
substantial wider societal impact. Currently, international screening detection rates are
highly variable, and are strongly dependent on the skill and experience of the sonographer
performing the examination.
This project builds on iFIND (www.ifindproject.com), a Wellcome Trust (WT) Innovative
Engineering in Health award, which has yielded powerful computerized technology that
uses artificial intelligence to simplify and enhance fetal US screening by automating many
routine tasks. This technology has been created by a fully integrated team of computer
scientists and clinicians working together using a close couple cycle of innovation and
clinical testing. It has the potential to have a significant impact on fetal screening, but to
achieve that it is necessary to transition from University developed prototype to healthcare
product. The usual strategy is to license to an existing player or spin-out a company.
However, in both cases the close coupling between technology innovation and clinical
testing that has proved so effective can get stressed or broken. We propose an innovative
approach in which the next stage of development is undertaken by an embedded team of
engineers working directly within a clinical environment. This will provide opportunities not
available by either of the conventional routes, providing an effective pathway to impact.


Research Resources Award

Dr Aileen O'Carroll, Dr Natalie Harrower, Mr Kevin Long

Digital Preservation of Reproductive Health Resources: Archiving the 8th On 25th May 2018, Irish citizens voted to remove the controversial "8th Amendment" to the Irish Constitution, opening the way for the introduction of legislation governing the termination of pregnancy in the State.

This project intends to provide long term preservation and access to the many at-risk archives generated by grassroots women’s reproductive health movements during the campaign.

There is no consensus on the best practice for archiving social media posts, which are supported on third party platforms. It has also been argued that archival curation has been skewed towards the dominant culture. As a result, many of the rich archives of reproductive health generated through the referendum campaign are at-risk.

This project aims to

·         Ingest material from the six collaborating organisations for long term preservation in the DRI

·         develop best practice for archiving social media

·         create a registry of at-risk reproductive health archives and support further ingest to the DRI

·         carry out social science research into best practice, ethics and legalities of archiving this material

·         Provide training and expertise to reproductive health archives in archival best practice

·         Collect and preserve additional material on the topic from the public


Research Resources Award

Introducing Assyrian Medicine: healthcare fit for a king This project makes available for the first time the world’s most standardised, structured and systematised corpus of medical literature prior to Galen: the "Nineveh Medical Encyclopaedia" from the library of Ashurbanipal, King of Assyria (669-c.630 BC). Its broken condition and its use of cuneiform script mean that, almost 200 years after their first discovery, still only glimpses of its content are accessible to medical historians. As such the importance of Assyria’s contribution to the history of medicine remains unrecognised.

While fragments of Ashurbanipal’s medical library have long been known, the existence of the Encyclopaedia has only recently been recognised thanks to the reconstruction and translation of an ancient medical catalogue. This discovery allows us now to reconstruct the whole Encyclopaedia from its broken fragments and translate it in full. We will then generate a complete index of drug names and technical vocabulary as found in the compendium, and correlate them against the symptoms they were designed to treat. All this material will be made freely available in enriched digital form. The project will therefore enable researchers to gain a clear understanding of ancient Assyrian medicine and its place in the broader history of medicine.


Research Resources Award

History Bones: opening up the archive of the Brittle Bone Society The project will catalogue the archive of the Brittle Bone Society which is primarily held by the University of Dundee Archive Services. Any material remaining at the Society headquarters will be transferred and catalogued and the catalogue will be available online. The material will be re-housed into appropriate archival quality storage containers and a proportion of the material will be digitised. An additional element of the project will be to conduct oral history interviews with Brittle Bone Society members and staff which will become part of the Society's archive. A project board will oversea the progress of the project and will assist in organising a dissemination event.

 The archive will be fully catalogued allowing researchers to understand its content and identify relevant material
 The material will be properly preserved ensuring its long term survival
 The archive will be supplemented by recordings of people associated with the Society which add to the richness of the research resource
 Awareness of the archive and its research potential will be increased, as will the likelihood of further accruals of material in future
 Two interdisciplinary dissemination events will allow the discussion of archives relating to disability and the Brittle Bone archive in particular

Grants awarded from 1 October 2005 to 30 June 2021


Research Resources Award

Building a Healthier City 2: slum clearance, council housing and renovation in Bath, 1890-1995 The project will open up valuable new opportunities for research into the relationship between housing and health, answering a clear need for easily accessible archival resources for studies of housing at a local level. It will enable access to significant records relating to slum clearance, provision of council housing, and renovation of unfit properties in Bath between 1890 and 1995. These records are currently uncatalogued and in a poor state of preservation, inaccessible to the research community.

We will catalogue approximately 90 linear metres of records to ISAD(G), and publish the resulting catalogue online; the records will be repackaged in accordance with BS4971:2017; remedial conservation will be carried out on those records requiring it. The activities of the project will be strengthened through the input of an Academic Advisory Board which will advise on interaction with the research community and dissemination of the project.

As a result of the project, access to a significant collection of records will be assured for researchers now and in the future. It will make a valuable contribution to the evidence base for research into the relationship between local housing policy and health, encouraging a long-term perspective on current housing issues, and informing future policies.


Discretionary Award - OPOH

Health-sensitive Implementation of Nationally Determined Contributions There is strong evidence that climate change presents severe health risks, while addressing the drivers of climate change can bring large health gains. Nationally Determined Contributions (NDCs) reflect countries' self-defined efforts to reduce greenhouse gas emissions, and adapt to climate change impacts, to meet the goals of the 2015 Paris Climate Agreement.  They are renewed every five years, beginning in 2020. The first round of submitted NDCs are neither sufficient to limit warming below the global goal of 2C (aiming at 1.5C) nor to adequately strengthen resilience to climate risks. While 65% cite health, less than 25% include health cobenefits of mitigation, only 3% of proposed NDC actions connect to health, and only 50% of surveyed countries have a health adaptation strategy or plan.

The project will address barriers that currently hinder governments in systematically considering health in NDC design and implementation.  It will provide national health and development actors with evidence, analytical and capacity building tools to support them in integrating health risks, and the health co-benefits of climate change mitigation, into NDCs.  It will thereby contribute to protecting and promoting health, and to a more coherent and synergistic approach to climate action, health and sustainable development.


Building Becontree

Research Resources Award

Building Becontree This 18-month project aims to improve the accessibility of collections related to the construction, development, and management of the Becontree Estate through a programme of cataloguing, conservation, digitisation, and outreach utilising the following collections:

 Building and estate plans
 London County Council Property Management Files
 Tuberculosis and Infectious Disease Registers
 The Dagenham Digest
 Community publications - tenants’ handbooks, tenants’ gazettes, gardening guides
 Medical Officer of Health reports
 Rent books

Key outcomes:

 Creation of fully searchable catalogues to file- and item-level adhering to relevant international standards hosted on the Valence House Collections website and the Archives Hub
 Conservation, including repair of damaged plans and registers of infectious diseases and the repackaging of other materials using suitable archival-quality packaging
 Digitisation of key records - building and estate plans, tuberculosis and infectious disease registers, and Dagenham Digests - and long-term preservation of digital surrogates
 Creation of a project website for dissemination of digitised materials, publication of blogs, and facilitating of comments/memory-sharing from Becontree residents past and present
  Ingest of public comments from the website into archive catalogues
 Outreach activities engaging local residents and aiming to build a stronger lasting relationship with an academic audience
 Writing of research guides to all Becontree-related collections


Sir Henry Dale Fellowship

Understanding the impact of ‘near-coding’ variation in human disease Rare diseases (prevalence   250 million people globally. Current approaches for identifying the genetic cause of a disease focus on regions of the genome that code directly for protein, finding a disease-causing variant in only ~50% of cases.

My aim is to identify novel genetic variants outside of these protein-coding regions that lead to disease, and the mechanisms through which they do so.

I will do this by applying computational and statistical methods to pioneering large-scale genomic datasets, totalling ~700,000 individuals.

My approach will focus on ‘near-coding’ regions, defined as those directly adjacent to protein-coding sequence that have important functions regulating protein expression. I will use complementary approaches that (a) look for near-coding variants in rare disease patients without a causative coding variant and (b) assess the strength of negative selection acting on categories of near-coding variants to predict which are deleterious and cause disease.

The findings from my work will be translated into clinical care to enable more patients to receive a valuable genetic diagnosis. In addition, increasing our understanding of the near-coding variant types that are deleterious will inform on genetic mechanisms underlying disease and suggest novel therapeutic strategies.


Research Resources Award

Speaking Out: Cataloguing advocacy, support and empowerment in the Lothian Gay and Lesbian Switchboard archives Speaking Out aims to catalogue, rehouse and selectively digitise archives created by the Lothian Gay and Lesbian Switchboard (LGLS), an activist-run mental and physical health service for LGBT people in the Lothians and beyond. The project will disseminate its findings to academics and the wider public, and address key ethical, visibility and sensitivity issues through collaborative engagement with scholarly and stakeholder communities.

Opening on 2 March 1974, LGLS was the UK’s first gay helpline and Scotland's first gay charity. Despite this pioneering history, LGLS archives remain largely invisible to researchers in their current, uncatalogued state. This project aims to open up this collection to researchers through:

 cataloguing and indexing compliant with archival standards, at levels ensuring maximum general research access;
 identifying sensitivities/ethical issues and applying appropriate closure periods;
 using anonymised transcription to provide a way in to selected otherwise-confidential records (encouraging academic researchers to apply for access through established procedures);
 rehousing records in archival-quality storage;
 digitising selected material (such as locally-specific newsletters unavailable elsewhere in physical or digital form) to aid no-cost, remote research;
 promoting the collection to research audiences through targeted activities;
 recording a small number of oral histories (3 – 5), adding context for researchers.


PhD Studentship (Basic)

Investigating hormone secretion in response to altered nutrient delivery to the distal gut After a meal, enteroendocrine cells (EECs) along the gut sense nutrients. One type of EEC, the L-cell, responds by releasing hormones like GLP-1 which primes the body to deal with increased blood sugar by instructing the pancreas to release insulin. Gastric-bypass surgery leads to weight loss and in patients suffering from type 2 diabetes can also reverse this disease state, with increased GLP-1 credited in part for this. Blocking SGLT1 (a transporter needed for glucose uptake from intestine to bloodstream), also improves blood sugar control through increased GLP-1 secretion.

How gastric-bypass or blocking SGLT1 affect GLP-1 secretion is not fully understood but we believe a possible explanation in both cases is that nutrients are present or broken further down the gut than in normal physiology and that these breakdown products are promoting GLP-1 release from resident L-cells in the distal gut. We will study the gut contents of mice after SGLT1 inhibition or gastric-bypass surgery compared to normal mice after a meal. Any candidate break-down products will then be tested on isolated L-cells to measure GLP-1 response. Mimicking GLP-1’s effects forms the basis for many anti-diabetic drugs and we therefore hope that our study may lead to new treatment opportunities.


Discretionary Award - Public Engagement

BSA - public engagement with health research The British Science Association is proposing a new funding scheme to support public engagement with health in the UK.  This new fund will: take a more outcomes-focussed and targeted approach to working with applicants; support and foster innovation; and encourage the sector to diversify its approaches and audiences.

We are proposing a three in one scheme: an ‘Incubator Fund’ will provide smaller grants to support innovation and diversity, the ‘Main Fund’ will establish and expand proven links and approaches, while a ‘Discretionary Fund’ will allow us to invest in organisations or approaches that show particular promise.

As a result, the public engagement with health sector will benefit from a grants scheme that’s more flexible and easier to navigate. This will help support and diversify the applicant pool, and hence benefit the public who will be more empowered to engage in research and better equipped to interact with health researchers, or people in allied careers, on topics they’re interested in. Ultimately more people in the UK will be engaged with - and trusting of - health research, and be able to access its benefits.


PhD Studentship (Basic)

Protein Interactomes of Alzheimer’s Disease Risk Genes in Microglia Alzheimer's disease is a fatal condition with currently no cure. In our aging population, it is more important than ever to find ways to treat Alzheimer's, or even prevent it. Understanding the biology of Alzheimer's is a key step to understanding the disease and finding the best possible treatment and preventions. Previous research has found mutations in key genes, mostly expressed in microglia (the brain's immune cells) that increase a person's risk of developing Alzheimer's. Our work will focus on 3 of these genes (ABI3, TREM2, and PLCG2) and will look at how the proteins they code for interact with other proteins within cells.

We will do this by mapping which proteins interact with our proteins of interest, both the normal and mutant versions, then compare these interactomes. We will then investigate the function of any new proteins found in these results and finally assess if these new proteins also contain mutations that carry a risk for Alzheimer's.

This impact of this research will be to broaden our understanding of how these mutations increase the risk of Alzheimer's and may highlight potentially druggable targets to treat or reduce the risk of developing Alzheimer's.


Detecting Ebola at the Last Mile

DFID-Wellcome Epidemic Preparedness Grant

Dr Cheikh Tidiane Diagne, Dr Ousmane Faye, Dr Joe Fitchett

Detecting Ebola at the Last Mile Ebola virus disease has been declared a Public Health Emergency of International Concern in Democratic Republic of the Congo.

In the short term, our consortium plans to optimise, manufacture, and validate a novel Ebola rapid diagnostic test  (RDT) for deployment at the point of need — that is low cost and high performance. A simple, 5 minute, high performance test, that complements complex laboratory tools, is urgently needed to ensure earliest possible detection of Ebola in the heart of communities experiencing an outbreak.

Successful deployment will lead to an optimised and evaluated device for manufacture to support the current outbreak in DRC, surveillance in neighbouring regions, and in time post-DRC outbreak surveillance.

In the long term, we envision substantial impact  generated by establishing a new model for sustainable delivery of high performance outbreak diagnostics, deployed at the point of need. Accordingly, diaTropix - a new manufacturing facility dedicated to epidemics and neglected diseases in Dakar, Senegal - will be set up with the capability, expertise, and reagents to produce rapid diagnostics responsively to evolving outbreaks — with Ebola demonstrating proof of concept and feasibility, and a portfolio of rapid diagnostics in the pipeline for dengue, yellow fever, measles, and malaria.


PhD Studentship (Basic)

Developing de-novo assembly tools to predict gene transcriptional markers of severe malaria disease and ways to prevent it 219 million cases of malaria occurred globally in 2017. Vaccine development is considered the most cost-effective tool to combat malaria, however identifying suitable vaccine targets is problematic. Malaria disease can have many different symptoms and overall severity. Differences in disease severity have been associated with the parasite gene expression, polymorphisms within a gene and splicesome variation. However, quantifying transcript abundance of highly polymorphic genes is extremely difficult. This research aims to produce a pipeline that assemblies and quantify the abundance of these highly polymorphic genes. I will then investigate the degree of polymorphism for genes expressed in the mosquito stages of Malaria, as this is thought to be the most promising stage for identifying vaccine targets.


PhD Studentship (Basic)

Investigating compounds to increase the efficacy of antimicrobials used for targeting Helicobacter pylori The bacteria Helicobacter pylori (H. pylori) is a pathogen that infects the stomach of ~50% of the population, and can led to the development of peptic ulcers and gastric cancer. Although the treatment currently consists of a triple therapy of antibiotics and proton pump inhibitors, many strains have developed a resistance to antibiotics, and the disease can recur within a patient. H. pylori also colonises the stomach within a thick mucus layer, which can prevent drugs from reaching the site of infection. Two compounds have been found to increase the effectiveness of antibiotic therapy against resistant strains within patients; bismuth salts and the long term use of aspirin. I will conduct further research on ways to use these therapies in combination with antibiotics in order to provide a more effective treatment. I will also explore the possibility of encapsulating bismuth salts in a protective protein shell (apoferritin) to aid drug delivery across the stomach mucous. Using additional treatments alongside the antibiotics in treating H. pylori infection may increase their efficacy, and prevent the disease recurring. Elimination of the disease in a patient would also reduce the need for repeated antibiotic treatment, which can lead to incidences of antimicrobial resistance.


UMURINZI - Unprecedented Movement to drive a Unified Rwandan Initiative for National ZEBOVAC Immunization The ongoing outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of Congo (DRC) is of particular concern for the Government of Rwanda, when one considers the high population density of Rwanda and the number of people crossing the border between Rwanda and DRC on a daily basis. Janssen Vaccines and Prevention B. V. (Janssen) and the Rwanda Ministry of Health have recently entered into an agreement for a donation of 200,000 doses of the Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine. Rwanda FDA has granted conditional approval of the vaccine under exceptional emergency circumstances in accordance with SAGE recommendations to put in place approvals for investigational medicines and vaccines as an immediate priority for preparedness.

This Ebola vaccine initiative consists of: 1) a mass vaccination campaign that will target up to 193,000 individuals crossing or living in sectors/districts sharing the border with DRC; this program is known as UMURINZI (Unprecedented Movement to drive a Unified Rwandan Initiative for National ZEBOVAC Immunization); 2) a clinical trial to evaluate the immunogenicity of the vaccine regimen in 2,000 people; 3) and a clinical trial to evaluate the safety of the vaccine among 5,000 pregnant women.

This proposal concerns start up of UMURINZI only.


PhD Studentship (Basic)

Developing Machine Learning Approaches for Survival Analysis and Patient Stratification in Inherited Cardiac Conditions Inherited Cardiac Conditions (ICCs) include a variety of diseases for which the genetic basis and pathogenesis is still majorly unexplained. The clinical outcomes of patients with ICCs are very diverse, rendering diagnosis, prognosis, and accurate therapeutic decisions very challenging. The purpose of this project is to develop machine learning approaches that will be able to explain some of the survival and clinical differences among patients with the same ICC and describe genetic biomarkers responsible. This will enable better patient stratification which will lead to more accurate diagnosis and assessment of therapeutic actions that need to be taken. The modelling approaches will be based on cardiac imaging and genetic data collected from patients across the ICC spectrum and healthy volunteers.


PhD Studentship (Basic)

Atomistic Simulations of Cardiac Troponin Troponin plays an essential role in the skeletal and cardiac muscle contraction process which is mediated by sarcomeric Ca2+ concentration. Phosphorylation on cardiac troponin complex changes troponin's Ca2+ sensitivity hence modulates heart rate. Several point mutations on thin filament disrupt the heart’s normal contractile functionality and eventually lead to inherited cardiomyopathies. It was shown that in the mutated troponin tissues the myofilament Ca2+ sensitivity is not reduced upon phosphorylation by protein kinase A, and this relationship is termed the uncoupling phenomenon. In a recent study of small molecules related to the natural products EGCG and Silybin we found 22 small molecules that were capable of specifically restoring the coupled relationship between Ca2+ sensitivity and phosphorylation state, and these compounds are termed recouplers.

In previous studies, our group has attempted at elucidating the changes in protein dynamics introduced by phosphorylation and TNNC1 G159D mutation. In this project, we aim to use molecular dynamics simulations to reveal the underlying mechanisms of recouplers. We hope that with a deeper understanding of the molecular mechanisms of both the disease-causing mutations and the recouplers, we can take a rational approach in designing novel therapeutic compounds that are effective in treating cardiomyopathies while having minimal side-effects.


Discretionary Award – C&S

Early Modern Satire of Experimental Medicine in Spain (1493-1700) The project will bring to light the forgotten satiric traditions that accompanied the rise of experimental medicine in early modern Spain. Focusing on previously untapped archival and printed sources of Spain, the research will recover literary satires on diverse aspects of medical experimentation, including pharmacological trials, blood transfusions, and surgical experiments. These novel experiments prompted questions regarding the choice of patients, which frequently came from the dispossessed social groups, such as prisoners, soldiers, foreigners, servants, the poor, hospital patients, and asylum in-mates. Satire is inextricable from its public function and can therefore provide a valuable contribution to the understanding of the early modern medical experimental practices. The project aims to answer the following questions: How did satirists react to the choice of experimental bodies? What were their main concerns and how did they express them via the available satiric models? In what ways did physicians themselves use satire to discredit their rivals’ methods? Apart from yielding self-standing results in the form of two research articles and an online database, the research in Spain will prepare the ground for the investigation of satires of experimental medicine in Germany and the Netherlands.


PhD Studentship (Basic)

Time Series based dimension reduction methods on scRNA-seq data for Alzheimer's disease 1 in every 14 of the elderly in the UK has Alzheimer’s disease (AD). Identifying early warning signs of AD can provide great clinical benefits. Recent research suggests there are different possible mechanisms leading to the disease and a long-standing hypothesis that the building up of beta-amyloid proteins is the cause of the disease is shown not to be totally true. The mechanism of AD varies between population and different stages of the disease. Rigorous statistical methods are required to study the heterogeneity of the disease. Existing theory on the pathology of AD suggests physiological cycle involving different types of cells in the brain, suggesting it is important to consider the differences of each cell in identifying candidate genes that are differentially expressed.

The research will improve existing dimension reduction and clustering methods on single-cell RNA sequencing data. Time series analysis techniques will be considered so to identify changes of gene expression across different stages of the disease.

The research will allow a better understanding of the progression of AD and in another similar neurodegenerative context. Potential therapeutic targets can then be identified with a better understanding of the disease mechanism.


PhD Studentship (Basic)

Role of Golgi cells in the cerebellar granule cell layer The cerebellum is a brain structure that contains over half of the mammalian brain's neurons. The majority of inputs of the cerebellum enter the granule cell layer, which is therefore called the input layer of the cerebellum. Within this layer, two neuronal populations exist: excitatory granule cells and inhibitory Golgi cells. The latter play a fundamental role in balancing granule cell responsiveness, driven by pre-cerebellar inputs. Understanding the contribution of these inhibitory neurons to granule cell layer activity is indispensable to unveil cerebellar functions. To do so, we will manipulate activity of neurons within this network, by chemical means, in behaving mice. During these manipulations, we will be recording neural activity as well as behavioural parameters. From these data, it will be possible to better understand how inhibition controls excitatory neuron activity, what is the processing of cerebellar inputs operated by the granule cell layer, and cerebellar cortex computations. We will substantiate our work with tools of computational neuroscience that will allow us to formalise our findings.

Grants awarded from 1 October 2005 to 30 June 2021