Dr Jeroen Kool, Prof Stephen Ward, Prof Paul O'Neill, Prof Robert Harrison, Prof Neil Berry

Discovery and early translation of small molecule toxin inhibitors for use as broadly effective, inexpensive, oral, prehospital snakebite treatments Small molecule toxin inhibitors offer great potential to rapidly deliver inexpensive, safe and efficacious oral interventions in the community soon after a snakebite, prior to subsequent admission to a healthcare facility. Despite such promise, only a handful of toxin inhibitors have been robustly explored to date. We redress this here by expanding the chemical space available for snakebite treatments by employing a comprehensive drug discovery approach. Using toxin-specific assays, we will screen diverse compound libraries ( > 50,000 molecules), including using the Human Pharmacopoeia and Phase-1 approved molecules in a repurposing approach, for hits that demonstrate broad toxin family neutralisation. Thereafter, we will rationally identify lead series by defining the toxin-specificity, kinetics, phenotypic potency and medicinal chemistry characteristics of hits, before performing murine preclinical efficacy and pharmacokinetic experiments to rationally define oral dosage regimens of lead candidates capable of achieving systemic inhibitory concentrations throughout a snakebite treatment period. Finally, we will evaluate therapeutic combinations of lead candidates by performing dose optimisation via PK/PD modelling, and preclinical efficacy and drug-drug interactions studies. This comprehensive drug discovery pipeline will deliver a portfolio of lead candidates (and numerous backups) ready for translation into clinical studies to assess their tolerability and efficacy as next-generation snakebite therapeutics.


Snakebite Grant – Next Generation Treatments

Snakebite Advisory Panel (one-off committee)

Design, selection and validation of nicotinic acetylcholine receptor mimicking molecules as novel ‘decoy receptor’ therapies for treating snakebite One of the most common lethal snakebite pathologies is neurotoxicity, which is the result of neurotoxins blocking nerve transmission, commonly via interaction with nicotinic acetylcholine receptors (nAChRs). Here we will use molecules that mimic the structural components of nAChRs that are important for toxin binding to generically inhibit the functional activity of venom neurotoxins. Our pilot data demonstrates that such ‘decoy receptors’ offer great potential to generically neutralise venom neurotoxins irrespective of snake species (unlike antivenom).

We will use structural and informatic guided approaches to rationally design a panel of acetylcholine receptor binding proteins, nAChR ligand binding domains, and peptide mimotopes, before measuring their binding affinity to venom neurotoxins. We will then identify the toxins they capture using analytical approaches, before demonstrating that they effectively prevent binding to nAChRs. Thereafter, we will use in vivo efficacy studies to robustly assess whether mixtures of lead decoy receptors protect mice from venom lethality, as either solo or adjunct therapies.

We anticipate that our inhibitory mixtures will exhibit superiority over antivenom by neutralising neurotoxins irrespective of the snake species and at lower therapeutic doses. This project therefore has the potential to generate a single, generic, eminently translatable therapy for treating neurotoxic snakebites worldwide.

Grants awarded from 1 October 2005 to 30 June 2021

Creative Commons Attribution 4.0 International (CC BY 4.0)


Dr Devin Sok, Dr George Oluoch, Dr Kartik Sunagar, Dr Nicholas Casewell, Prof Christiane Berger-Schaffitzel, Prof Imre Berger

Novel platforms to develop polyspecifically-effective, safe, affordable and thermostable monoclonal camelid VHH nanobodies to treat snake venom-induced necrosis in India and sub-Saharan Africa 400,000 tropical snakebite victims require, every year, life-saving surgical debridement/amputation because there is no medicine to treat the disabling, income-depleting effects of snake venom-induced necrosis. A new therapy is urgently needed to prevent the severe health and socioeconomic consequences upon already-impoverished victims and health facilities.

Our evidence-underpinned hypothesis is that rationally-selected recombinant, humanised camelid VHH targeting necrosis-inducing venom toxins (NITs) will possess the efficacy, rapid in-tissue distribution, safety, thermostability, affordability and large scale production characteristics appropriate for future development of a community-dispensed therapy – a paradigm shift in the clinical management of venom-induced necrosis to reduce morbidity.

To achieve this for Africa and India, our partners bring new approaches, platforms and all required resources to select candidate recombinant NIT-specific monoclonal VHH from (i) B cells of NIT-immunised camels and (ii) a synthetic VHH library - complementary approaches maximising likely success.

Deploying sequential in vitro, ex vivo human skin and mouse in vivo assays of venom-induced necrosis enables down-selection of the most efficacious, thermostable recombinant VHH. ‘Humanising’ the latter donates the key safety criterion. E.coli expression enables inexpensive and large-scale production of humanised VHH. These therapy-characteristics and the vast panAfrica/India need, provide economy-of-scale production incentives for future manufacturing partners.


Antibody Discovery and Development Against Non-Immunogenic Snake Venom Toxins  This proposal aims to ultimately reduce global levels of morbidity and mortality from snakebite envenoming by discovering and developing antibodies that can neutralize the low molecular weight snake venom toxins – key contributors to the disease. These non-immunogenic toxins are poorly neutralized by currently available antivenoms produced by animal derived immunizations. This proposed project will discover neutralizing antibodies through immunization experiments using rationally designed immunogens and select for high-affinity antibodies via synthetic libraries using recombinant toxins.


Black Health and the Humanities

Discretionary Award – C&S

Black Health and the Humanities The project will establish an interdisciplinary network of researchers with the aim of investigating and bringing to light perspectives from the Black humanities on Black health and wellbeing. Led by the Centre for Black Humanities at the University of Bristol, the project will consist of a series of video conferenced online workshops, symposiums and events, which will: a) create a community of scholars whose research concerns how Black writers, intellectuals, artists, activists and theorists have creatively and critically addressed the psychological and physiological health of black people across the twentieth and twenty-first centuries; b) explore how research in Black humanities might intervene in the current racialized landscape of medicine and health; c) train and develop a new generation of ECR scholars in the theories and methods of Black studies and the medical humanities and in how they insect.


Recombinant snakebite antivenom for sub-Saharan Africa Sub-Saharan Africa (sSA) is heavily burdened by snakebite envenoming. Existing antivenoms are scarce and many have suboptimal therapeutic properties. To improve snakebite envenoming therapy, the application of carefully designed mixtures of fully human monoclonal immunoglobulin G (IgG) antibodies for systemic and nanobodies for locally acting toxins poses as not only a therapeutically promising, but also scientifically feasible solution. Therefore, taking advantage of our well-established discovery pipelines and expertise in working with oligoclonal and broadly-neutralizing antibodies against toxins, we will develop a broad-spectrum (polyvalent) recombinant antivenom for sSA. The project will focus on the following technical goals that we believe have a potential to deliver measurable societal and humanitarian health impact: 1) The identification and isolation of all medically relevant snake venom toxins that need to be neutralized by a recombinant antivenom for sSA and 2) the discovery of a well-characterized panel of broadly-neutralizing IgGs and nanobodies that can neutralize all medically relevant systemically-acting and deep tissue penetrating toxins found in the 24 medically most relevant snake species from this region. Combined, these efforts will create a substantial shift in snakebite envenoming therapy and will enable the clinical development of improved, low-cost, and quality-assured snakebite therapeutics for victims in sSA.


Investigator Award in Science

Neutrophils re-entering the circulation from a primary site of inflammation:  Physiological or pathological? Neutrophils contribute to the killing and clearance of pathogens as well as initiate inflammation resolution and tissue repair processes. Furthermore, the established phenotypic and functional diversity of neutrophils have markedly extended the physiological and pathological roles of these myeloid cells. Building on the developing concept of neutrophil heterogeneity in disease settings, and significant mechanistic and pathophysiological data from the applicant, the present project aims to acquire an in-depth understanding of one population of disease-inducing neutrophils, namely neutrophils that have exhibited reverse transendothelial cells migration (rTEM). This phenomenon describes cells that initiate diapedesis, engage with endothelial cell (EC) junctions but then exhibit retrograde motility and re-enter the vascular lumen. Crucially, we have ample evidence that rTEM bestows an activation state on neutrophils in vivo, and that rTEM neutrophils are aligned with remote organ damage. Thus, exploiting recent technological advancements and capabilities, the current proposal aims to gain an in-depth understanding of the prevalence, molecular signature and pathogenic role of this "subset" of neutrophils, most notably in ageing. Furthermore, hypothesizing that the activation state of rTEM neutrophils maybe beneficial for the host, the project will for the first time explore the potential protective, and thus physiological, role of rTEM neutrophils against pathogens.

Transendothelial and Transepithelial Migration


Discretionary Award – Directorate

M72 Phase 2 Trial: Safety & Immunogenicity in People Living with HIV The aim of this proposal is to obtain co-funding from the Wellcome Trust for a Phase 2 safety and immunogenicity trial of the M72/AS01E investigational vaccine. This Phase 2 trial in people living with HIV (PLHIV) is conducted to support inclusion of PLHIV in a following pivotal Phase 3 VE trial and to thus enable public health use of the vaccine in PLHIV should the Phase 2 and Phase 3 data support its use. PLHIV are at high risk for TB disease and deaths, and an estimated 251,000 of 1,450,000 deaths from tuberculosis in 2018 occurred in PLHIV.

The key deliverables of the full program (Phase 2 and 3) are:

 Advance technical and clinical development of the M72/AS01E candidate vaccine from Phase 2b through Phase 3 (including Mtb uninfected and HIV-positive populations) and prepare for licensure
 Identify a marketing authorization holder willing and capable to file the licensure application(s) and manufacture global product supply and to ensure global access to the vaccine
 Aim for initial registration in South Africa to enable Phase 4 impact studies (outside the scope of this proposal) that generate robust effectiveness data for the prevention of TB in children and adults


Clinical Research Career Development Fellowship

Myocardial energy starvation and ketone metabolism in patients with type 2 diabetes Patients with type 2 diabetes(T2D) are ‘cardiac energy-deficient’ and this deficiency contributes to their excess heart failure(HF) risk. The key mechanisms for cardiac energy deficiency are reduced myocardial blood flow, loss of metabolic flexibility over the choice of energy fuels and mitochondrial dysfunction. The contribution of these changes to the development of HF has not been systematically studied.Recent studies have highlighted the potential role of ketone bodies as a significant fuel source, and suggested an association between mild ketosis and improved clinical outcome in T2D.

Two work packages will be performed. Work-package1 aims to:

 Elucidate the mechanisms of the energy-starved state of the heart in diabetes;
 Determine how alterations of cardiac energy metabolism differ between prediabetes, T2D, and concomitant T2D and HF;
 Determine if ketones induce a differential response in mitochondrial respiration and whether this differential response varies along the continuum of diabetic heart disease.

Data will be acquired from patients undergoing aortic valve surgery for comprehensive assessments including: cardiovascular magnetic resonance imaging and spectroscopy; coronary sinus sampling studies; high resolution respirometry and liquid chromatography-triple quadrupole-mass spectrometry metabolomics from heart samples.

Work-package 2 will explore the impact of ketone infusion on cardiac energy generation and contractile function in T2D patients.


Innovations AIGH Enterics Flagship

Wellcome/GAVI Innovations Enterics Flagship

The Impact of Mass Oral Cholera Vaccination in Uvira, South Kivu, Democratic Republic of the Congo In this study co-funded by Wellcome and Gavi, the aim is to study the impact of mass
cholera vaccination in Uvira, DR Congo through a multifaceted approach aimed at estimating
changes in clinical disease incidence, infection rates, and the type and frequency of
occurrence of toxigenic V. cholerae in the environment. Successful completion of this project
will provide critical insights into the impact that mass OCV campaigns can have on human
health while at the same time providing a new understanding of the epidemiology of cholera
in this hyper-endemic setting. Our specific objectives are:
Objective 1: To enhance the cholera surveillance system in Uvira, South Kivu, DR Congo in
order to estimate the impact of mass vaccination on lab-confirmed cholera incidence and
mortality.
Objective 2: To conduct serial cross-sectional serosurveys after vaccination to estimate the
seroincidence of V. cholerae infection in Uvira over time and contextualize the primary
results based on clinical cholera cases.
Objective 3: To use phenotypic and molecular methods to describe the changes in the V.
cholerae population after vaccination in both human and environmental samples in Uvira.
Objective 4: To use phenotypic and molecular methods to describe the changes in the V.
cholerae population after vaccination in both human and environmental samples in Uvira.


Health communication research

Discretionary Award - OPOH

Health communication research Air pollution is a global health emergency. Outdoor air pollution causes 4.2 million premature deaths every year and 90% of these deaths happen in low- and middle-income countries. Additionally, air pollution has significant overlaps with climate change, both being caused in large part by the combustion of fossil fuels. While the link between air pollution and climate change isn’t always straightforward, smart solutions can ensure a win-win.

A survey commissioned by the Clean Air Fund (CAF) found that health professionals are the most trusted spokespeople on air pollution in all countries.[1] Consequently, there is an important opportunity to encourage real change if the health sector could be engaged as spokespeople to reduce air pollution, which has been further strengthened by COVID-19.

In this application we propose research on communications strategies that spur action on air pollution by healthcare practitioners. CAF is already funding such work in UK, India and at a global level. Additional support would add Bangladesh, Mexico and Ethiopia. Outputs include strategic recommendations for communicating on air pollution in the respective countries, as well as a database with existing campaigns and their effectiveness.

[1] Research carried out in May 2020 in the UK, India, Poland, Bulgaria and Nigeria.


Discretionary Award - Open research

Designing a Preparedness Model for the Future of Open Scholarship Over the next 12-18 months, leading structures relied on to conduct, publish and disseminate scholarly research are at risk of collapse.

One leading use case to illustrate the current reality as it unfolds, and how it will affect scholarly research communications is the impact on university and scholar led presses, and the risks that presents to the creation of scholarly monographs.

University presses are collectively facing unprecedented deficits and sales shortfalls for print books this year. Budget constraints at the library level may well directly affect the sale of scholarly monographs as well as subsidies and subventions.

To address this potential threat to scholarship, we are launching a cross-institutional research effort to address pending infrastructure consolidation and collapse across the ecosystem, identifying the opportunities, leverage points, costs and approaches that could be employed.

The project sets out to deliver the following:

 Cost-benefit analyses to enable faster, more informed decision making in support of open scholarship;

 Criteria for assessing solutions in service of the academy;

 Actionable recommendations and guidance for budget owners;

 Actionable recommendations and models for projects to operate sustainably;

 Scenario planning for 6, 12, and 18+ months outlooks;

 A collective model for stewardship, cost-sharing, and risk pooling.


Sir Henry Wellcome Postdoctoral Fellowship

Elucidating the structure and function of the divergent and essential cytochrome bc1 complex in apicomplexan parasites Apicomplexan parasites, which include Toxoplasma and Plasmodium, cause deadly human diseases, such as toxoplasmosis and malaria. Understanding their divergent cell biology could inform strategies to combat them. The apicomplexan mitochondrial electron transport chain (mETC) is essential for their survival and transmission, and highly divergent from the human mETC. Cytochrome bc1 is an mETC protein-complex that is essential, and a key target for drugs, like atovaquone. Yet its composition is unknown, and the mechanism of function and inhibition poorly understood. I propose to investigate how the cytochrome bc1 complex functions and interacts with inhibitors.

Using Toxoplasma as a model, I will uncover the role of my newly discovered apicomplexan cytochrome bc1 subunits, and decipher the role of respiratory super-complex formation, in parasite energy metabolism and survival. Using cryo-EM technology I will solve this complex’s structure to elucidate its mechanism of action, highlighting key differences with the human complex, and understand the way inhibitors disrupt the electron flow essential for energy conversion.

These studies will provide a mechanistic understanding of the essential apicomplexan cytochrome bc1 complex and how inhibitors stop its function. This work will fill a critical gap in our knowledge of fundamental parasite cell biology, and likely inform drug discovery.


Genomic epidemiology of acute respiratory distress syndrome and fibrosis in patients with COVID-19 COVID-19 is an infectious respiratory disease with a global devastating health impact. Genetic and environmental factors influence COVID-19 susceptibility and outcomes, including the development of acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. These lung pathologies have a high mortality and there are no specific treatment options or effective prognostic methods for patients. Therefore, there is an urgent need to identify effective biomarkers of disease prognosis. The aim of this research is to perform a genomic epidemiology study of ARDS and pulmonary fibrosis in patients with COVID-19. For that purpose, we will perform genetic overlap studies that will include genetic correlation analyses, polygenic risk score approaches, and assessments of overlap of individual genetic variants, followed by fine mapping studies, bioinformatic approaches to identify the likely causal genes, and further experiments to evaluate their role in disease and their potential as drug targets. Results of these analyses will allow us to identify novel genetic risk factors and to develop risk prediction models, which could enhance COVID-19 patient stratification for those at increased risk of lung sequela. Furthermore, the project will reveal novel therapeutic strategies, which would translate into improved and more personalised clinical care for patients at risk of lung fibrosis.


Career Re-Entry Fellowship

Extracellular polycation signalling in alveolar and systemic inflammation Critically ill patients with pneumonia often have impaired neutrophil function and disruption of alveolar-capillary barrier integrity. During inflammation, excessive polycation generation activates the calcium-sensing receptor (CaSR), which can potentially compromise neutrophil function and barrier integrity. My over-arching hypothesis is that, during critical illness, CaSR, activated by polycations, mediates impairment of neutrophil, alveolar epithelial and pulmonary endothelial function, leading to reduced bacterial clearance and disruption of alveolar-capillary barrier.

To test the hypothesis, I shall use a range of complementary methods to (a) assess the effect of positive and negative allosteric CaSR modulators and polycations on a range of functions in neutrophils and monocytes from critically ill patients at high risk of developing nosocomial infection; (b) isolate human primary alveolar epithelial cells and culture primary human pulmonary microvascular endothelial cells, and assess the effect of CaSR modulators on barrier function, inflammatory signatures, and antimicrobial functions; (c) perform the first temporal assessment of CaSR expression (and effect of CaSR inhibition) in extravasated neutrophils and alveolar macrophages from human healthy volunteers receiving inhaled lipopolysaccharide (LPS) or control; and (d) create neutrophil-specific CaSR knockout mice, assessing the influence of neutrophil CaSR on the natural history of acute pulmonary infection, inflammation, and alveolar-capillary barrier disruption.


Mapping sensory-motor cerebellar circuits for adaptive behaviour The cerebellar cortex is thought to form predictive associations between sensory inputs and motor commands: animals leverage these associations to coordinate and adapt movements to contextual changes in the environment. This sensory-motor control depends on Purkinje neurons, each of which receives sensory, motor and cognitive signals from one climbing fibre as well as thousands of parallel fibres, the axons of granule cells. Despite years of anatomical work, cerebellar sensory-motor representations have not been mapped at the cellular scale; similarly, the functional circuit connectivity underlying sensory-motor integration remains unexplored.

To reveal the functional architecture of the mouse cerebellar cortex, I propose to use rabies monosynaptic tracing to map and functionally characterise the presynaptic ensemble of individual Purkinje neurons. I will validate my functional connectomics strategy with electron microscopy and elucidate whether the anatomical organisation of presynaptic circuits converging on Purkinje neurons is modular or random (Aim1). Then, I will harness functional imaging and optogenetics to map the topography of cortico-cerebellar representations, and discover whether Purkinje neurons pool inputs from related sensory-motor presynaptic modules (Aim2). Finally I will train mice in a sensory-guided forelimb task, and ascertain how these circuits are engaged by sensory-motor events, and their timing, during adaptive behaviour (Aim3).


Determining the role of inter-kingdom interactions in the evolution of antimicrobial resistance  Polymicrobial infections consisting of Aspergillus fumigatus and Pseudomonas aeruginosa are associated with poorer patient outcomes and are often much harder to treat. There are a very limited number of drugs available to treat fungal infections, and both bacterial and fungal resistance is rapidly spreading in environmental and clinical settings. Determining the effect of inter-kingdom interactions between these pathogens upon the evolution of antimicrobial resistance is vital for the treatment of polymicrobial infections.

Multispecies biofilms caused by coinfection of these two key respiratory pathogens create a physical barrier preventing drug penetration leading to protection from antimicrobial treatment. However, we understand very little about how competitive interactions within such communities can alter the mutational drivers of resistance or how coexistence changes the pleiotropic fitness costs associated with resistance. The aim of the project is to understand how coexistence and competition between A. fumigatus and P. aeruginosa alters the rate of resistance evolution in the presence and absence of antimicrobial treatment and how interactions change the fitness landscape of resistant mutants within both species.

Understanding the drivers of resistance in polymicrobial communities may increase our ability to predict resistance evolution and aid the design therapeutic of strategies that limit the emergence of resistance.


Prof Kenneth Harris, Prof Matteo Carandini, Prof Ilana Witten

Dopaminergic reorganisation of cross-region neural communication Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to provide a reinforcement signal that is essential for learning. Despite recent advances, how VTA-DA neurons coordinate and modulate communication and synaptic plasticity across brain regions to drive behavior is still an open question. We hypothesise that 1) DA enhances communication of behaviorally relevant information across cortex and striatum and 2) the content of the information varies across corticostriatal regions. To test this model, we propose an ambitious research program in mice, using state-of-the-art in vivo electrophysiology, optogenetics, neuropharmacology and computational techniques. First, we will use high density in vivo electrophysiology (Neuropixels) to record neural activity across different corticostriatal regions, while optogenetically manipulating VTA-DA neurons in mice performing a visuospatial decision-making task. We will then use advanced computational methods to examine how and what information is communicated across corticostriatal regions, and how this process is modulated by DA. Finally, we will causally evaluate how DA mediated changes in cross-region communication depend on the receptor, synapses and the neuronal populations involved. In conclusion, we propose a comprehensive study of how DA modulates cross-region communication to drive behavior, providing a needed bridge between our systems and synaptic level understanding of VTA-DA.

Grants awarded from 1 October 2005 to 30 June 2021


Dr Claudia Langenberg, Prof Cecilia Lindgren, Prof Wiebke Arlt, Dr Hilary Finucane

A genomics approach to unravelling the link between steroid hormone dysregulation and cardio-metabolic disease Steroid hormone dysregulation has been linked to nearly all leading causes of death, notably cardio-metabolic diseases. Despite this, the aetiological contribution of steroid hormones to such disease is poorly understood and its potential as a therapeutic target remains largely unexplored. To fill this gap, I seek to pioneer a new aetiological understanding of steroid hormone dysregulation and its health consequences through multiple complementary data-driven approaches. I will do the following:

 Identify the genomic basis of steroid regulation through large-scale genetic studies of steroid hormones, steroidogenic enzymes, and regulating peptides.
 Pinpoint the tissues, genes and biological mechanisms involved in steroid dysregulation in men and women, through the vertical integration of genetics with tissue-specific molecular trait data. As part of this, I will set up an omics atlas of the adrenal gland and the ovary.

 Map out the metabolic and regulatory relationships between steroid hormones and related traits through the identification of genetically determined multi-dimensional steroid traits.

 Conduct a genomics-driven identification of new therapeutic pathways and protein targets to correct disease-causing steroid imbalances.

In short, this research agenda will not only uncover the aetiological pathways linking the steroid endocrine system to cardio-metabolic disease, but also instigate novel treatment strategies.


Dr Martin Bishop, Dr Davor Pavlovic, Prof Igor Efimov

Development of novel computational approaches for human cardiac mapping data - Improving understanding and treatment of atrial fibrillation   Cardiac arrhythmias are a common pathway for multiple cardiovascular diseases, the leading cause of death in the world. Ablation of cardiac arrhythmias is a recommended and common treatment option for arrhythmia patients, but success rates are poor. Cardiac electroanatomical mapping systems (EAMs) are used to identify ablation targets. EAMs generate a wealth of raw data that is ideal for developing algorithms to tailor treatments to an individual patients’ pathophysiology and improve treatment options. However, no platform exists for developing and testing algorithms.

Specific groups have developed closed-source software to identify ablation targets however, these results have not been widely reproducible. There is an acute need for an open-source and cross-vendor EAM analysis software to facilitate sharing methods, increase rigor and transparency and increase access to advanced processing tools.

I will develop expandable open-source software for analysis of EAM data. I will incorporate established and novel analysis methodologies, including machine learning approaches. Algorithms will be robustly validated using clinical, pre-clinical and in silico datasets. The software I will develop will enable myself and others to utilise routinely collected clinical data, to better treat cardiac arrhythmia. I will apply these approaches to identify mechanistic drives of atrial fibrillation as an exemplar application.


Discretionary Award - Policy

Global Healthcare Innovation Alliance Accelerator

Enhancing and refining the GHIAA MAPGuide GHIAA started the process of transforming its ‘paper’ Master Alliance Provisions Guide (MAPGuide) into an online resource in autumn 2019. Using Wellcome’s funding, GHIAA has made significant progress towards developing an intuitive, user-friendly tool, and a robust online platform to support future growth.

The development process began with creating a prototype MAPGuide tool and conducting initial stakeholder consultations in January and February 2020. These consultations provided vital input on adjustments needed to improve the user experience with the online tool. Driven by that input, GHIAA has recently completed significant improvements to the beta version of the MAPGuide.

During additional consultations in June 2020, stakeholders provided encouraging and constructive feedback on the improvements to the features and functionality of the MAPGuide. The next step in the development process is a public launch, targeted for early August 2020.

GHIAA is seeking further funding from Wellcome to:

 Conduct additional consultations for wider stakeholder groups over the rest of 2020
 Make additional improvements based on feedback identified through consultations and user surveys after rollout
 Conduct targeted workshops on potential future features and improvements
 Conduct a consultative process to advance the Global Health Transactions Glossary
 Develop additional content, features and supporting tools for the MAPGuide


Dr David Entenberg, Prof Valerie Brunton

Intravital imaging as a platform for screening checkpoint and focal adhesion kinase inhibitors as potential treatment for cancer metastasis Despite new developments in treatment, cancer remains the second leading cause of death worldwide. Breast cancer is the most common cancer within the UK, with death generally caused by the formation of metastasis. I intend to investigate the hypothesis that immune responses at the metastatic site determine the long-term outcome of therapy.

I will compare immune responses at the primary and metastatic sites upon administration of checkpoint inhibitors that have different clinical success rates. Flow cytometry and t-SNE analysis will provide insight into the affected cell populations and timings.  I will then utilise newly developed intravital imaging technologies to visualise immune responses in vivo at multiple cancer sites. I will measure cytotoxic cell activity and tumour cell death as indicators for anti-cancer response. Further, I will examine the ability of a combination of checkpoint inhibitor and focal adhesion kinase inhibitor to fully eradicate tumour cells. An inhibitor will be fluorescently tagged to study its access to tissue and interaction with immune cells dependent on combination therapy.

The proposed research will help to elucidate the role of immunotherapy on the metastatic foci and will provide the first insights into the benefit and limitations of combination therapy on secondary site immune responses.


Prof Annette MacLeod, Prof Luis De Lecea

Molecular basis of parasite-induced disruption of host circadian outputs  Sleep/wake cycles are arguably the most important circadian behavioural output controlling many aspects of animal physiology. However, some infections induce disruptions to these cycles, leading to pathology. Sleeping sickness is an infection caused by the African trypanosome Trypanosoma brucei. One of the most puzzling symptoms of this disease is the profound alteration in sleep patterns, which is now recognised as circadian disorder. This disease provides an ideal framework to study how pathogens disrupt host circadian behaviour.
I will use single-cell transcriptomics to profile the responses of key hypothalamic nuclei controlling circadian behaviour during infection. I will also characterise the population of parasites residing in the brain compared to bloodstream parasites to identify mechanisms of glial activation, neuroinflammation, and parasite survival in the CNS. These outputs will provide novel and unprecedented insights into the host-pathogen interactions in the hypothalamus that lead to disruptions of sleeping patterns.
My ultimate aim is to understand how pathogens interfere with the function of the central nervous system leading to changes in physiology and behaviour. The outcomes of my fellowship will provide a new understanding of infection-induced circadian disorders and will reveal factors that can be exploited for intervention and treatment of infections affecting the brain.


Dr Andre Marquand, Prof Andrea Mechelli, Dr Ferath Kherif, Dr M Jorge Cardoso, Dr Vince Calhoun, Prof Philip McGuire

Using multimodal normative modelling to predict clinical outcomes in early psychosis Individuals at the early stages of psychosis already suffer from neuroanatomical, neurofunctional and neurocognitive alterations. However, it is not clear how these alterations interact with each other and, more importantly, how this interaction may help predict who will become unwell. The aim of the proposed study is to uncover previously hidden relationships between brain anatomy, function and cognition that can improve our understanding of the first signs of the illness and help predict illness trajectory at the individual level. This will be achieved by triangulating, for the first time, data fusion, machine learning and a unique longitudinal dataset of individuals at the prodromal stage or with a recent first episode of psychosis. This combination of methods will allow me to address three main objectives: 1) identify previously unknown relationships between anatomy, function and cognition in healthy individuals; 2) develop a model that captures the normative pattern of these hidden relationships and determine by how much each patient deviates from this pattern; 3) use these deviations to predict each patient’s longitudinal clinical outcomes. I will also develop an open access tool that allows non-expert researchers to perform data fusion on their own data. Keywords: psychosis, data fusion, machine learning, outcome prediction.


Investigating the role of gut macrophages in mediating alpha-synuclein pathology in Parkinson’s disease The gut-brain axis is at the heart of Parkinson’s disease (PD) etiology. Pathological alpha-synuclein accumulates early in the gut, potentially affecting the enteric nervous system (ENS) and spreads to the brain. However, we lack insights into how pathological alpha-synuclein affects ENS integrity and cellular mediators underlying their spread. Here, I propose to study the role of a unique subset of gut macrophages (gMacs), the ENS-gMacs, that coordinate neuronal function in their unique ENS niche. I hypothesize that ENS-gMacs critically dependent on LRRK2 for alpha-synuclein clearance. LRRK2 is a risk factor for PD, regulates alpha-synuclein clearance in macrophages and is highly enriched in ENS-gMacs compared to microglia and neurons. First, using state-of-the-art single cell RNA and in-situ sequencing techniques I will examine how ENS-gMacs and microglia become dysfunctional in PD mouse models. Second, using in vivo and in vitro tools, I will dissect whether mutant LRRK2 signaling in ENS-gMacs affects neuronal function and survival upon PD patient-derived pathological alpha-synuclein. Finally, I will investigate how ENS-gMacs contribute to alpha-synuclein pathology and spread. Insights obtained will create new avenues to study neuroimmune pathways along gut-brain axis for the future, as well as novel targets for early therapeutic interventions in PD.

Leucine-Rich Repeat Serine-Threonine Protein Kinase-2


Innovator Award

Prof Jeremy Lambert, Dr Stephen Martin, Prof Simon Ward

Developing small molecules as a neurosteroid replacement strategy for treating postpartum psychosis After giving birth, some women have the rapid onset of a severe mental health condition, postpartum psychosis, with mood symptoms, hallucinations and delusions. Postpartum psychosis is a medical emergency due to the risk to both mother and child. During pregnancy there is an increase in circulating hormones called neurosteroids and these enter the brain and change the function of proteins called GABA-A receptors. In order to adapt, the brain reduces the amount of these proteins but following the rapid drop of neurosteroids after birth, the GABA-A receptors cannot recover to their pre-pregnancy levels quickly enough and therefore normal brain function is compromised, triggering postpartum psychosis. Our aim is to identify a synthetic neuroactive steroid that can compensate for the postpartum loss of natural neurosteroids and thereby reduce the symptoms in affected mothers and also prevent episodes in women at high risk. This will be of enormous benefit to women and their families.


Discretionary Award - Public Engagement

Public involvement to shape policies and solutions on antimicrobial resistance To address the problem of antimicrobial resistance (AMR) in Thailand, the Thai government produced the "Thailand National Strategic Action Plan on Antimicrobial Resistance 2017-2021" (TNSAP). While public engagement sits at the heart of the TNSAP, Thai campaigns so far have predominantly focused on raising awareness through educational materials and events like the annual AMR Week, but less on patient and public involvement in shaping the national AMR response. In our project, we will bring together adult audiences (e.g. patients, consumers, young professionals), non-governmental organisation representatives, AMR researchers and national policy makers to co-create an AMR stakeholder map, an AMR engagement strategy, and context-specific solutions to reduce the burden of AMR. The project will be implemented over 18 months, employing Wellcome’s Responsive Dialogues approach to design and implement a combination of in-person regional Conversations and nation-wide virtual Conversations. Our main outcomes are (1) improved understanding and engagement with the issue of AMR among adult Thai communities (2) changes in the national AMR policy to include context-specific solutions and (3) improved understanding about the implementation of Wellcome’s ‘Responsive Dialogues’ toolkit in Thailand. Our project will be integrated into the activities implemented within the current TNSAP and inform the next TNSAP .


Prof Jason Barton, Prof Mairead MacSweeney

Sir Henry Wellcome Postdoctoral Fellowship

Understanding the mechanisms of multimodal communication in deaf children with cochlear implants Children develop and interact in complex, multimodal environments. I will investigate how deaf children with cochlear implant (CIs) integrate visual information from the talker’s face to supplement sound.

This is important because CIs provide a degraded sound that lacks pitch and much affective information, placing high cognitive demand on the developing brain and increasing reliance on visual information and audio-visual integration.

I will conduct experiments comparing adolescents with early-onset deafness and bilateral CIs to hearing controls. Eye tracking will be used to understand allocation of visual attention during word and emotion perception and the interaction between these processes. Visual evoked potentials will be measured using electroencephalography to understand the efficiency of cortical processing during visual perception.  Psychophysics and pupillometry will be combined to estimate the benefit gained from audio-visual speech integration and the impact on cognitive effort. Functional near-infrared spectroscopy will enable cortical imaging of CI users without interference from CI-generated artefacts. Correlations between activity in temporal and occipital cortices will be examined to understand audio-visual cortical connectivity and to specify mechanisms of audio-visual integration.

This work will enable us to better understand the role for visual cues in augmenting current auditory-only rehabilitative interventions to help deaf children communicate effectively.


Prof Robert Brownstone, Dr Claire Meehan, Prof Ole Kiehn

Dr Filipe do Nascimento Xavier Fernandes

The contribution of spinal inhibitory circuits to aberrant excitability in Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease targeting motoneurons, leading to paresis and death. Changes in spinal microcircuits have been suggested to be part of an early homeostatic response to preserve motor output, possibly involving substantial alterations at the level of premotor synapses. Supported by solid preliminary data, I hypothesize that changes in these circuits precede motoneuron degeneration, and thus propose to address these aims: (1) define early disruptions in connectivity to motoneurons in ALS and (2) determine the genetic profile of these abnormalities. I will characterize well-known spinal synaptic pathways such as Ia excitation, disynaptic reciprocal inhibition and pre-synaptic inhibition in wildtype mice and 2 different models of ALS (SOD1G93A and TDP-43-A315T). I will do this both in vitro, by using a novel isolated mature mouse spinal cord preparation, and in vivo by performing intracellular recordings of motoneurons and EMG recordings with chronically implanted multielectrode arrays. These experiments will be complemented with transcriptomic analysis using single-cell patch seq and laser capture microscopy to reveal if changes in specific spinal microcircuits are accompanied by changes in expression profile of motoneurons and interneurons. This project will reveal if early degeneration in ALS results in generalized circuit impairment.


Don't sugarcoat it: understanding and targeting glycosylation changes in pancreatic and liver cancers Pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) are leading causes of cancer-related deaths. Despite knowing these cancers’ driver mutations, there are no effective therapies. A universal yet understudied feature of both PDAC and HCC is their aberrant glycosylation. Glycosylated serum proteins act as clinical biomarkers, but it is unknown how altered glycosylation – driven by gene expression changes and mutations of glycosyltransferases/glycosidases – contributes to disease progression.

First, I propose to establish a new HCC mouse model combining genetic alterations with chronic alcohol consumption, a major risk factor. Second, I will systematically uncover the glycosylation changes in primary cells of this new HCC model and established PDAC models using unbiased mass spectrometry-based glycomics and lectin microarrays. By applying glycobiological techniques to this setting, I will bring together two hitherto disparate research fields. Third, based on these data, I will manipulate the glycosyltransferases/glycosidases most likely responsible for the glycosylation changes and examine disease progression, yielding new targetable oncogenes. In parallel, based on preliminary data, I will investigate the tumour suppressive mechanism of the fucosidase FUCA1 in mouse models of PDAC and HCC, using glycomics as a starting point. Finally, I will validate my findings in human PDAC and HCC samples.


Discretionary Award - Policy

A Unit for Health Evidence and Policy in Laos There is a need to build capacity and improve evidence-informed decision-making concerning resource allocation and priority-setting in health in low- and middle-income countries, such as Laos. This kind of capacity building and institutional strengthening is all the more important in an era of aid transitions and uncertainty related to the current COVID-19 pandemic, to enable Laos to continue progressing towards Universal Health Coverage.
We propose the creation of a Unit for Health Evidence and Policy (UHEP)  based in the University of Health Sciences in Vientiane, to enhance the use of research evidence to inform policy. UHEP will focus on health technology assessment (HTA) as a tool to enable priority-setting.
We aim to complete four main activities for this pilot project over one year.

 Situational analysis of the Lao health policy context including stakeholder mapping
 Training of Lao researchers and policy makers in HTA and on synthesis and use of research evidence (includes funding for one MSc student)
 Development of a roadmap for institutionalisation of rational priority setting in health policy development in Laos
 Selection and implementation of a pilot HTA project

At the end of this year UHEP will be established as a government technical partner for HTA in Laos


OA Switchboard 2020

Discretionary Award - Open research

Open Access Scholarly Publishers Association (OASPA)

OA Switchboard 2020 Throughout 2020, a project is run to prepare for the OA Switchboard (a collaboratively developed and community run open source solution) to go live as an operational solution. The OA Switchboard provides essential infrastructure and back office services to facilitate the fulfilment of open access strategies across business models, policies and agreements via: 1. communication standards (‘metadata’); 2. technical solutions (‘hub’); 3. standardised real-time monitoring and reporting.

The essence of the problems it aims to address as a priority:

 It is complicated/cumbersome to find out how to get the service charges for a certain OA publication settled, and to prepare for (enable) such financial settlement
 It is a challenge to monitor funds and track spending in real time

In the current situation, enabling open access to scholarship has never been more pressing. Supporting the OA Switchboard is investing in open source infrastructure that will ensure that transformational change to open access can be achieved by all publishers, whilst reducing complexity for funders, institutions and researchers. It will also work alongside and strengthen other initiatives that the Wellcome Trust is supporting in this space, specifically in realising the synergies of interlinking the Journal Checker Tool and the OA Switchboard.


Meat Your Persona

Discretionary Award - Public Engagement

Meat Your Persona Meat Your Persona will further the public’s understanding of the connection between their meat consumption and its environmental and health impacts and will empower them with accessible information and tools to make better informed choices about their consumption.

Building on the successful pilot (https://www.youtube.com/watch?v=QbHb4ap39nw), we propose a national tour, taking Meat Your Persona to audiences at urban and suburban shopping centres and community hubs. Our goal is to reach those with low science capital who are disconnected from the current conversation. In particular we will target Brexit-voting men outside London who are the most likely to eat the most meat and to not connect meat consumption with health and environmental impacts.

We will capitalise on renewed public interest in evidence, using creative design methods to convey key facts from the LEAP research so that people are able to make better informed choices. We will actively signpost people to a purpose-built website where they can receive evidence-based support to reduce their meat consumption. The project will be evaluated independently to see if we have achieved our three goals: to drive behaviour change, build public trust in science and inform research through advancing the public conversation.


Global Goal: Unite for Our Future

Discretionary Award - Policy

Global Goal: Unite for Our Future Global Citizen and the European Commission ran a campaign, Global Goal: Unite for Our Future, with the aim of ensuring that everywhere in the world, those who need them have access to COVID-19 tests, treatments, and vaccines. The campaign also sought to lessen the impact of COVID-19 on the world’s most vulnerable people, ensuring they still have access to education, clean water, and more.
The campaign, launched under the patronage of European Commission President Ursula von der Leyen, focused on the development of tools to tackle COVID-19, and ensuring that these tools are available to all communities equally, as well as mitigating the impacts of COVID-19 on those living in poverty.


Epidemics Ethics

Coronavirus

Epidemics Ethics With this proposal we seek to establish a global community of bioethicists (to be known as 'Epidemics Ethics') combined with a range of online resources and activities together capable of providing real-time, contextually appropriate support to assist researchers, policy-makers, communities, and responders in identifying, analysing and addressing ethical issues arising in the context of global health emergencies. Epidemics Ethics will complement the newly established Public Health Emergency Preparedness and Response Ethics Network (PHEPREN) by providing: timely responses to ethical problems, access to networks of experts, an array of online resources including seminars, workshops, blogs, and ethics briefings on issues of current concern. A key aim of Epidemics Ethics will be to support the establishment of fair, collaborative partnerships to enable ethics research to be conducted by ethics scholars in low and middle-income countries in the context of broader supportive international collaborations. With this in mind, capacity building will be a key focus.


Discretionary Award - Open research

Full text COVID-19 preprints in Europe PMC In this pandemic, researchers have responded by publishing results rapidly, often through preprints. In fact, about half of the publications in Europe PMC on COVID-19 are preprints rather than peer-reviewed journal articles. Currently, the full text of these preprints are scattered as PDFs on preprint servers, or, available as a non-standard set of documents for machine learning purposes. This proposal is about making the full text of COVID-19 preprints available on Europe PMC, a large and sustainable life sciences archive, for reading and reuse via a standard XML format, alongside peer-reviewed full text articles. Being able to easily search and read preprint full text on a site already frequented by millions of users a month, means that they will be significantly more discoverable by people, and will be able to make use of existing infrastructure to integrate into the typical ecosystem of publications - for example, linking to related data - as well as being more open to scrutiny. This will accelerate scientific research on COVID-19, provide an opportunity to build new open and rapid publication systems, and form a corpus for future history of science research.


COVER

Coronavirus

COVER With the rapid development of candidate vaccines for COVID-19, this project will identify and provide guidance on a range ethical issues arising in the development and deployment of COVID-19 vaccines. Over the next six months, the COVER project will concentrate on the ethics of vaccine research and development—including phase 3 trial design and equitable inclusion of special populations in the research agenda, with a particular focus on pregnant women as well as population groups that have or likely will experience disproportionate burden from COVID-19. This project will also conduct formative landscaping work on the ethical challenges and tradeoffs in the allocation and deployment of vaccines, both globally and within nations. This work will lay the groundwork for normative guidance and mathematical models to best inform policymaking once efficacious vaccines become available for wider use, with explicit consideration and assessment of how various approaches will not only impact the trajectory of the COVID-19 pandemic overall, but also how the benefits of vaccination will be fairly distributed across different population subgroups. In addition, the COVER project will begin to address ethical issues of COVID-19 vaccine development and deployment specific to Africa, with a concentrated body of work in Nigeria.


Discretionary Award - OPOH

The benefits of decarbonised electricity generation in cities   While prior national level and regional studies have evaluated the contribution of coal combustion on air quality-related health impacts at the national or regional level, a concrete understanding of how coal combustion impacts urban populations can make a strong case for the rapid phase-out of coal-fired electricity generation in cities around the world.

Project aims:

(1) demonstrate a strong urban case for a rapid-phase out of coal-fired electricity generation; and (2) utilise the research results for an effective advocacy and communications campaign at COP26.  In the research project, C40 will estimate the contribution of coal combustion for C40 city electricity generation to global GHG emissions, to air quality-related health burdens in C40 cities, to COVID-19-related health impacts as well as analyse the economic benefits of different coal phase-out scenarios by looking at: (1) the economic value of improved health associated with reduced coal combustion for electricity generation in C40 cities; and (2) the number of net jobs that are generated with a switch from coal combustion to clean energy.

Grants awarded from 1 October 2005 to 30 June 2021


Discretionary Award - Public Engagement

UK Association for Science and Discovery Centres (ASDC)

Resilience and Digital Engagement in the time of Coronavirus. ASDC Proposal for A National Support Programme for UK Science Centres The Vision: To support the UK Science and Discovery Centres in response to Coronavirus, by creating and delivering a National Resilience Programme accessible by all UK charitable Science Centres, and to further support the sector through a Leadership and knowledge exchange programme, and a Digital Resilience Programme working with Communities across the UK.

The Mission: To develop and deliver a National Resilience Programme to enhance Resilience of UK Science Centres during this time of restrictions due to Coronavirus and to ensure this is adaptable to what is needed by Science Centres and remains relevant across 2020 and 2021. To select 15 UK Science Centres and grant-fund these as part of a National Digital Resilience Programme to engage, inspire and involve under-represented children, families and communities with STEM and to raise the profile of the UK Science Centres over the coming year.


Multi-User Equipment Grant

Multi-User Equipment and Technology Development Committee

Dr Harry Low, Dr Tiago Costa, Prof Xiaodong Zhang, Dr Alfonso De Simone, Dr Christopher Aylett, Dr Morgan Beeby, Prof Dale Wigley, Dr Doryen Bubeck, Prof Christian Speck

A modern cryo-EM instrument for biological samples at Imperial College London The Centre for Structural Biology at Imperial College London includes a heavily-used electron microscopy facility on the South Kensington campus that features four electron microscopes for single particle and tomographic analysis of biological samples. A large and rapidly-growing Imperial- and London-based user community spanning molecular biology, chemical biology, and drug development, uses these instruments for sample screening, optimisation, and data collection. These instruments, however, are all based on 20+ year-old archetype, resulting in rising maintenance costs and risk become irreparable any day due to inability to source replacement parts. These machines are also bottlenecks, incapable of providing high-throughput screening, optimisation, and data collection needed to feed high-resolution data collection instruments such as Titan Krioses accessible at various UK-based facilities. Our community is in urgent need of a contemporary electron microscope such as a Talos Arctica capable of both single particle and tomography cryoEM, equipped with technology for rapid screening and optimisation and compatibility with Krios sample handling. The instrument will be embedded and managed within the CSB EM facility and accessible by all CSB users on an hourly user rate basis to guarantee full cost recovery, a company-based service contract, and long-term sustainability.


Multi-User Equipment Grant

Accelerating analysis of viruses, vesicles and nanoparticles with nanoscale flow cytometry Multiparameter analysis of nanoscale entities such as viruses, nanoparticles and extracellular vesicles is restricted by the limited resolution of standard flow cytometers. Both the nanoparticle and extracellular vesicle fields are rapidly growing in the academic and commercial setting.

We are applying for a state-of-the-art dual-laser Flow NanoAnalyzer (model U30) from NanoFCM, as well as five years discounted servicing and support. The Flow NanoAnalyzer (FNA) is an innovative flow cytometer which has been specifically engineered to surpass the nanoparticle detection limitations of current commercial flow cytometers. In particular, the FNA enables detection of nanomaterials, nano-drug delivery systems, bacteria, viruses, cell organelles (e.g. mitochondria) and extracellular vesicles (e.g. exosomes and microvesicles) within a size range of 7-1000nm. The FNA is equipped with one highly sensitive side scatter channel, a 488 nm laser, a 638 nm laser and three single-photon counting module (SPCM) detectors (525/40 nm, 580/40 nm and  > 650 nm) to enable multi-colour/parameter experiments.

The FNA only recently launched in the UK (April 2019). Therefore, if funded, Imperial will become one of the first UK (and potentially European) universities to have this machine. This will attract significant interest from UK, as well as, international academic and industrial collaborators or users.


Multi-User Equipment Grant

Dr Marios Philiastides, Dr Robin Ince, Prof Peter Uhlhaas, Prof Satu Palva, Prof Gregor Thut, Prof J. Matias Palva

State of the art MEG-TRIUX-neo for advancing multi-modal neuroimaging techniques in Scotland Magnetoencephalography (MEG) is an advanced technology using super-conducting quantum interference devices (SQUIDs) for measuring the tiny magnetic fields produced by the coherent electrical activity in groups of neurons. MEG is the only neuroimaging technology that enables non-invasive recordings with both excellent temporal and good anatomical resolutions. Such spatiotemporal accuracy is instrumental for discovering the mechanisms underlying mental functions and deficits in healthy and impaired brains.

We seek Wellcome Trust funding to replace our 12-year old MEG system with a state-of-the-art TRIUX-neo from MEGIN Ltd. The TRIUX-neo is an ultra-sensitive system based on new technology that combines MEG recordings with high-density EEG, online head-motion tracking and a helium recycling mechanism now essential with worldwide helium shortage.

With the TRIUX-neo, our multi-user MEG group (with significant Wellcome Trust funding, Investigator, Innovator, Seed and Sir Henry Wellcome Fellowship) will keep enhancing its cutting-edge, unique, cohesive and collaborative research and pioneer new methods and techniques across our extensive platform of in-house imaging facilities (i.e. EEG, MEG, NIRS, 3/7T fMRI).

Key MEG innovations will focus on understanding brain network dynamics and oscillations in health and disease, using information theory and advanced network analyses and unique data fusion of EEG and 3/7TfMRI and neurostimulation (TMS, tES).


Multi-User Equipment Grant

Dr Matthew Gold, Prof Gregory Towers, Dr Anthony Roberts, Dr Nikos Pinotsis, Prof Snezana Djordjevic, Prof Finn Werner, Prof Trevor Smart, Prof Bonnie Wallace, Prof Frances Brodsky

Strategic upgrade of crystal monitoring and optimisation equipment at ISMB, as critical infrastructure for structural biology and biochemistry ISMB (Birkbeck/UCL) is renowned for its research in structural biology, successfully combining X-ray crystallography and electron microscopy and supporting users from a wider scientific community. The current set up for crystallisation includes a nanoliter liquid handler (Mosquito, SPT Labtech), an old Perkin-Elmer liquid handling robot for sample optimisation and an outdated Minstrel/Rigaku automated imaging suite. Recent crystallography beamline technological developments at high-end synchrotrons have pushed the boundaries of data collection and reduced the usable size of crystals down to a few microns. However, our current instrumentation does not allow us to take full advantage of these new technologies since refinement of crystallisation conditions, and monitoring of ‘microcrystals’ growth, cannot be managed by our outdated equipment. Moreover, two of the existing instruments are no longer supported by authorized services.

Therefore, we are requesting the purchase of a new state-of-the-art ‘imaging hotel’ (UVEXps, swissci) and liquid handler (Dragonfly, SPT Labtech). Specifically, we propose to purchase a microliter liquid handler for optimisation of crystallisation conditions and a high-resolution crystal imaging system for storage, monitoring, imaging and detection of protein crystals. The two instruments will complement the existing liquid handler (Mosquito), while offering more flexibility to all users by remote access.


Multi-User Equipment Grant

Prof Susan Burchill, Prof Robert Ariëns, Dr Jacquelyn Bond, Dr Patricija van Oosten-Hawle, Prof Andrew Wilson, Prof Michelle Peckham, Prof Nikita Gamper

Focussing on biomedical discovery in the North-East of England: A high-throughput/high-content live imaging system for cells, tissues and small model organisms The Flow Cytometry  &  Imaging Facility, Leeds Institute of Medical Research, needs to expand capability and capacity for live cell and high content imaging (HCI) to serve the local and wider scientific community. We request part-funding of a LIPSI high content/multichannel live-cell imager with environmental control (Nikon Instruments UK Ltd). The acquisition of a state-of-the-art LIPSI will replace our obsolete Operetta and Incucyte instruments and will transform our Facility by allowing fully integrated, automated, high-throughput, and high-content/live-cell imaging. The system allows very rapid epifluorescence (six simultaneous fluorescence channels), chromogenic and DIC acquisitions whilst running multiple time-lapse assays with sampling rates up to 60fps. This allows imaging of long-term live-cell 2D/3D cell cultures, tissue sections, small model organisms or rapid HCI of fixed cells. For increased throughput, the LIPSI includes motorised stage, robotic handler and environmentally-controlled plate-holder. This enables streamlined automated processing of multiplexed long-term live cell functional assays, with complex imaging schedules in both hypoxic and normoxic environments for up to 20 plates. Standard acquisitions comprise multichannel, time-lapse, multiple-positions, z-stacks, large images and multidimensional imaging using standard plastic or glass SBS plate, dish and slide formats used within the Facility.


LASCOPE extension

DFID-Wellcome Epidemic Preparedness Grant

LASCOPE extension The "Lassa fever Clinical Course and Prognostic factors (LASCOPE)" project is a prospective cohort study of patients with acute symptomatic Lassa fever (LF) hospitalized in dedicated treatment centers in Nigeria. The patients have access, free of charge, to reliable molecular diagnosis of LF, ribavirin therapy and an improved standard of supportive care including renal replacement therapy. This study aims at producing up to date data on LF disease presentation and course, management, outcomes and factors associated to fatality. The data produced by the LASCOPE study will inform the design of future trials evaluating innovative therapeutic strategies for LF, as well as the development of updated guidelines for the management of patients with LF. Lastly, this project will contribute to the development of clinical research capacities in the participating sites and put them in position to conduct future therapeutic and vaccine trials for LF.


Multi-User Equipment Grant

Dr Jamel Mankouri, Prof Nicola Stonehouse, Dr Andrew Tuplin, Dr John Barr, Dr Juan Fontana Jordan de Urries, Prof Adrian Whitehouse, Prof Andrew Macdonald, Dr Morgan Herod, Prof Peter Stockley

Live cell imaging capability for research on pathogenic viruses We request a 75% contribution to purchase two IncuCyte S3 Live-Cell Analysis Systems, together with archive data storage capacity (£189,485). These instruments are designed to acquire real-time growth, migration, morphology, phenotypic and gene expression data from virus-infected cells in microplates.  They will be located in newly-opened Biological Safety Level 3 (BSL3) and BSL2 laboratories, transforming existing capacity for real-time analysis of virus-infected cells and enabling ambitious plans for expansion of virology research.  The overall aims of the research supported by these instruments are: 1) to understand the molecular mechanisms by which viruses enter cells, replicate their genomes and assemble into infectious virions, and 2) to drive early-stage development of new anti-viral therapeutics (eg screening compound libraries).  The IncuCyte instruments will facilitate both work streams. They will be housed in standard cell culture incubators and can be remote controlled allowing the analysis of cell parameters over time safely without disturbance.  In order to effectively train users, provide technical advice, oversee usage and manage the instruments, we also request funding for 10% of the salary of the current BSL2/BSL3 laboratory manager, and 5% of the BioImaging facility support scientist over 5 years (£31,390).


Use of CGD to address DRIs in Kenya

Discretionary Award - Public Engagement

Use of CGD to address DRIs in Kenya Global action to tackle AMR is insufficient because public engagement on AMR is limited[1]. CGD[2] can help close this gap and help communities and decision-makers take collective action on AMR.

This project will apply CGD methods in three Kenyan counties over 14 months to empower communities, health-workers, researchers and policymakers to generate and use data on AMR. A robust scoping phase will involve stakeholder consultations to tailor CGD methods and engagement mechanisms to the local contexts. The project will have three tracks:

 Data to Empower: engaging citizens to better understand AMR related behavior and perceptions, and empowering citizens with objective and contextually relevant information
 Data to Give Direction: using CGD to empower citizens to change behaviors, fill evidence gaps for the research community, and support health policy decision-making,
 Advocacy on CGD: encouraging researchers and policymakers to incorporate CGD as an important source of evidence for more holistic AMR policies

[1] https://wellcome.ac.uk/reports/reframing-antimicrobial-resistance-antibiotic-resistance

[2] CGD is ‘data that people or their organisations produce to directly monitor, demand or drive change on issues that affect them. It is actively given by citizens, providing direct representations of their perspectives and an alternative to datasets collected by governments or international institutions’


Multi-User Equipment Grant

Dr Benedict Seddon, Prof Lucy Walker, Prof Claudia Mauri, Prof Emma Morris, Prof Paul Griffiths, Dr Joe Grove, Prof Benjamin Chain, Prof Mala Maini

Provision of multi-parameter fluorescence-activated cell sorting for functional and genomic analysis of immune cells This application is for the purchase of a BD Aria-Fusion fluorescence activated cell sorter.  The instrument performs high-speed multi-parameter sorting, allowing isolation of rare cell subsets and supporting single-cell genetic and functional analyses. It will enable scientists at the UCL Institute of Immunity and Transplantation (IIT) to be at the forefront of studies of the patho-physiology of the human immune system and responses to disease treatments.

This state-of-the-art sorter is essential to allow us to maintain a cutting edge flow-cytometry core facility in the newly constructed Pears building, which will house the IIT from late 2020.  The Pears building is a £61 million joint project between UCL and the Royal Free NHS Foundation Trust to create a world-leading centre for disease-focused immunology research. The building will accommodate some 20 research groups comprising approximately 200 scientists.  The translational immunology programs of the IIT include mechanistic studies in animal models, genetic and functional analyses of the human immune system, high-dimensional analysis of clinical samples and the monitoring of patients participating in novel immunotherapy trials. The technical capability of the FACS-Aria-Fusion is therefore required to support a wide variety of cutting-edge research programs in infection and immunity.


Multi-User Equipment Grant

Dr Elton Zeqiraj, Prof Mark Kearney, Prof Peter Stockley, Dr Stephen Muench, Prof Fiona Meldrum, Prof Sheena Radford, Dr Juan Fontana Jordan de Urries, Dr Rebecca Thompson, Prof Richard Bayliss

State of the art direct electron detection at the Astbury Biostructure Laboratory The Astbury Biostructure Laboratory, was established in 2015 with University of Leeds investment, and a Wellcome multi-user equipment award, allowing us to install two Titan Krios microscopes (2016). In just three years, we have established an international reputation for excellence in cryoEM, and a buoyant user base that means our facility is already operating at capacity. We request funds to upgrade our microscopes, aiming to increase data acquisition rates, whilst improving data quality, allowing us to shorten session lengths, increase sample throughput, and introduce new methodologies.

Upgrades will include:
1. A ThermoFisher Falcon-4EC camera on Krios#1
2. A Gatan Bioquantum K3 on Krios#2
3. Aberration-Free/Fringe Free Imaging Systems (both microscopes)
4. EPU-D software for electron diffraction (Krios#1)
5. Whole-system maintenance contract extensions to 5 years from installation.

We anticipate a 5-8x improvement in data acquisition, empowering users to drive more challenging biological and biomedical discovery. We will be able to determine new high-resolution structures and integrate them into their cellular/tissue context, helping us to understand the molecular basis of diseases such as infections, cardiovascular disease, degeneration and cancer.

We request £1m from Wellcome, with a University capital contribution of £325k, plus salary costs, Giving a total project cost of ~£2.13m.


Europe PMC 2021-2026

Discretionary Award – C&S

Europe PMC 2021-2026 In the next five years, the necessity for open science to solve global challenges will become increasingly apparent, and the need for Europe PMC as a critical piece of infrastructure will crystallise in the minds and usage patterns of researchers. The world of scientific publishing will undergo major changes, as routes for rapid and transparent publishing emerge, and efforts such as Plan S push towards universal open access. Europe PMC will support these goals by aggregating millions of articles and making them widely available. With a leading role in preprint aggregation and standards development, Europe PMC will be the go-to resource for searching life sciences literature from publication through review, revision, and citation. Publications at all stages need to be grounded in unambiguous links to supporting data, authors and reviewers, funding, and institutions, to build transparency and trust in the content; building these links will be a major direction for Europe PMC. Finally, transformative change in content search and retrieval will come from the development of AI methods that work on open access full text, encouraged by the Europe PMC platform for text and data mining, as well as the demonstration of machine learning benefits in user interfaces.


Three Photon Microscopy Suite

Multi-User Equipment Grant

Dr Andrei Kozlov, Prof Cristina Lo Celso, Prof Molly Stevens, Dr Julien Vermot, Prof Clare Lloyd, Dr Amanda Foust, Dr Christopher Rowlands

Three Photon Microscopy Suite We propose the establishment of a dedicated facility for three-photon live imaging of deep tissue. This will comprise a dedicated multiphoton microscope (Scientifica Hyperscope or similar) with optical components anti-reflectance coated for long-wavelength light (up to 1700 nm) for three photon imaging, together with a suitable laser excitation source. Funding is requested for a high power ultrafast laser (Amplitude Systems Satsuma 40/40 or similar) producing up to 40W at 1030nm, pumping an Optical Parametric Amplifier (APE/Amplitude Mango SP or similar) to produce 1150-1700 nm light at a 2 MHz repetition rate, optimised for three photon excitation of both green and red fluorophores. The microscope will be mounted on a single large antivibration table. The three-photon microscope will be installed in a Home-Office designated small animal imaging suite.  A dedicated facility manager (with substantial expertise of in vivo multiphoton imaging including biomedical optics), will run the facility, ensuring continued high imaging performance, and maximising effective and collaborative use of the facility. The imaging suite will provide a unique capability for deep tissue imaging by Wellcome Trust funded researchers across a range of biomedical application areas, including neuroscience, cardiology, stem cell biology and respiratory physiology.


Multi-User Equipment Grant

Prof Daniel Raleigh, Prof Sarah Tabrizi, Prof Giampietro Schiavo, Dr Alan Lowe, Prof Frances Brodsky, Prof Michael Cheetham

Expanding the proteomics and establishing top-down capabilities for the UCL Mass Spectrometry Science Technology Platform. The requested equipment is the ThermoFisher Orbitrap Eclipse Tribrid Mass Spectrometer with an Ultimate3000 LC system. This new instrument is designed for high-end proteomics, top-down protein characterisation, and crosslinking analysis and is equipped with the latest Orbitrap analyser, which offers higher resolution, sensitivity and acquisition rates compared to previous Orbitraps.

These features result in improvements to both limit of detection and quantification of peptides, ultimately leading to enhanced quantitative proteomics and crosslinking analysis.

Its atypical geometry allows multistage fragmentation of ions (MSn), which is necessary for multiplexed proteomics experiments and for advanced crosslinking analyses using cleavable crosslinkers. Combined with a novel in-built real-time search algorithm, fragment ions of interest e.g. crosslinked peptides can be preferentially selected, further increasing the depth of analysis. The Eclipse is also capable of top-down proteomics experiments which is an ideal method for the study of proteoforms and labile post-translational modifications.

We will use the Eclipse to study the biological processes underpinning viral secondary envelopment, type 2 diabetes, cell responses to protein misfolding and cell competition; these studies are challenging due to the low amounts of sample available. The sensitivity and robustness in protein quantitation provided by the requested instrument will be key for their success.


Multi-User Equipment Grant

Dr Paul Elliott, Prof Elena Seiradake, Prof Maike Bublitz, Dr Bungo Akiyoshi, Prof Colin Kleanthous, Dr Ivan Ahel, Prof Elspeth Garman, Prof Christopher Schofield, Prof Matthew Higgins

Advanced protein crystallography imaging system  Protein crystallisation continues to play a central role in structural biology as the foundation for determining the atomic structures of macromolecules, understanding disease mechanisms, vaccine design and drug discovery. Several challenges remain, including crystallisation of multiprotein complexes, membrane proteins and time-resolved studies from systems directly engaged in catalysis, cell signalling, and ion movement. Studying different levels of structural complexity and dynamics is essential to understand protein function in health and disease. Technical developments are contributing to progress in these areas, including X-Ray Free Electron Lasers (XFELs) and Serial Synchrotron (SFX) data collection, coupled with advances in crystal imaging, which enable researchers to identify microcrystals that were previously not detectable with older instrumentation. This proposal builds on these advances through the acquisition of cutting-edge instrumentation for protein crystallisation, including advanced UV and multi fluorescence imaging optics and lipid cubic phase fluorescence after photobleaching (LCP FRAP) systems, which will provide access to, and development of, novel methods to detect and grow protein crystals of challenging multiprotein systems. A new multiuser protein crystallisation facility, centred in Oxford Biochemistry, but incorporating several stakeholders from across the wider University research community, will provide access and training.


Discretionary Award – Innovations

OX79 Coronavirus Record Linkage Project - QResearch-ICNARC COVID-19 Collaboration: This project will undertake large scale data linkage between critical and primary care and
Public Health England to investigate the effects of routine medications and patient
comorbidities on the outcomes from COVID-19 disease.
Assessing the effects of routine medications on COVID-19 disease is important for two
reasons. Firstly, some medications have been suggested to make the disease worse. As a
result, patients and clinicians are unclear about whether they should be continued. Secondly,
some routine drugs may treat or lessen the effects of infection. Establishing whether peopleon particular drugs are less likely to get severe infection will help researchers find treatments
for the disease.
Identifying what types of patient are prone to get severe disease and how long term conditions
affect outcomes will help provide advice and target interventions to the right people.
Undertaking these objectives will allow us to develop a platform linking all the patients in the
primary care database to all the Public Health England COVID-19 tests undertaken and all the
patients admitted to an Intensive Care Unit. This platform will allow detailed assessment of the
course of patients during the COVID-19 outbreak, including assessment of the effects on health
for patients without COVID-19 disease.
This platform will also enable studies investigating health, medication and health resource use
before and after critical illness, accelerating development of a long term rich research resource.


Discretionary Award - Policy

UK contribution to development of a GDPR Code of Conduct
 Make a clear case for and facilitate UK involvement in the joint action with UK and EU stakeholders.
 Act as a secretariat to support the UK partner in the joint action.
 Prepare contingency plans for maintaining an influence in the absence of UK representation in the Joint Action.
 Gather a body of evidence of NHS and UK expertise on data processing in the health sector to contribute to the European Code of Conduct
 Maintain regular updates and briefings on the scope and objectives of the GPDR code of conduct, to maximise UK preparedness.
 Follow progress of Europe’s data strategy, the European health data space and the development of a legislative proposal on Artificial Intelligence, using the same UK stakeholder group to feed in expertise where possible and provide intelligence and updates on possible implications for the health sector.


Learned Society Curation Awards

Wellcome – HHMI Learned Society Curation Awards

Learned Society Curation Awards Expert Review Group

Transparent Peer Review for Open Science and Research Assessment A scaleable, interoperable mechanism to establish transparent peer review in scientific journals and preprints as a standard optimized for the browsing, interpretation and assessment of research papers and preprints. The proposed tools and standards will allow inclusion of peer review formally in research assessment by funders and research institutions.


Multi-User Equipment Grant

Dr Arthur Pratt, Dr Caroline Wilson, Prof Matthew Collin, Prof Muzlifah Haniffa, Prof Matthias Trost, Prof Sophie Hambleton, Dr Christopher Duncan, Dr Daniel Rico, Dr Gary Reynolds

Spectral Flow Cytometry (SFC) for profiling single cells of the immune system in health and disease Multi-dimensional single cell analysis using cytometry technologies is one of the most significant contributors to our understanding of complex cellular compartments such as the immune system.  In recent years we have seen an explosion of new technologies and methodologies that have expanded the number of parameters per cell such as scRNA-seq, but we have suffered from an inverse correlation with scalability and throughput due to significant associated costs.  Our goal is to successfully introduce Spectral Flow Cytometry (SFC) as a new, sensitive, scalable and future proof multi-dimensional single cell phenotyping technology to the vibrant, multi-user core facility.  We will use the immense capabilities of SFC to understand rare immune-deficiencies (Hambleton); decode the developing blood and immune system (Haniffa); dissect the role of macrophages in inflammatory disease through somatic mutation analysis (Collin); unravel molecular processes in host-pathogen interactions that dictate immune responses (Trost); understand more about Giant Cell Arteritis (Reynolds), anti-viral responses (Duncan), immune surveillance of liver cancer (Wilson) and the control/relapse of Rheumatoid Arthritis (Pratt).  We will also address fundamental questions about the technology and methodology itself through expanding the parameter set using probes and label free measurements based on auto-fluorescence (Filby) as well as develop analytical tools (Rico).

Grants awarded from 1 October 2005 to 30 June 2021


Discretionary Award - Diversity and Inclusion

Improving mental health for marginalised groups at Oxford's Wellcome Centres
This proposal will address the intersection of mental health and Equality, Diversity  &  Inclusion (EDI) within Oxford’s three Wellcome Centres. Mental health concerns permeate a broad range of challenges relevant to EDI, including social exclusion, chronic illness and disability, and minoritised populations (detailed below) that are disproportionately affected by mental ill-health.

By identifying specific mental health challenges that different groups face, we can improve equality. Through normalisation of discussions around mental health in the workplace, and building an appreciation for how these issues affect people differently, we foster inclusion. If we can recruit and retain a broader range of researchers further into their careers, we improve diversity, and therefore our science. An increasingly inclusive, fair and kind research culture will lower the risk of mental ill-health for all our team and staff members within the high-impact but high-pressure academic environment.

Our specific objectives are to:
(i)  Conduct an in-depth, expert review of mental health as it relates to EDI within our Centre work environments.
(ii)  Implement recommendations arising from this review relating to policies, communication and practices.
(iii)  Build a broad, cross-Centre programme promoting positive research change around mental health and EDI.


WT/POST Fellowship

Secondment Fellowship Interview Committee

An Ethical Framework for WHO EVIPNet Policy Dialogues This research project will develop a framework for systematically incorporating ethical values into WHO Evidence Informed Policy Network (EVIPNet) Europe policy dialogues. Although ethical values are central to the appraisal of evidence and deliberation that is involved in policy dialogues, there is currently no explicit guidance for facilitators or participants on how to identity, define, interpret and evaluate key ethical values, nor how to recognise and work towards resolving tensions between different values. Explicit consideration of ethical values in this context is essential to the accountability and legitimacy of policy dialogues in the health policy decision-making process. Without it, discussions and decisions risk being shaped by unacknowledged and potentially unfounded assumptions, and risk recommending policy solutions which do not adequately take into account their moral and social costs and benefits. My project will aim to identify and evaluate the major existing accounts of moral reasoning for complex, real world deliberative contexts, and to develop and defend a model which is appropriate for policy dialogues. Policy dialogues are highly pragmatic tools which do not seek to pre-determine the values, knowledge and reasoning that participants bring to the table, and an ethical framework for this context must be similarly inclusive and pragmatic.


WT/POST Fellowship

The role of research and reflection in third sector responses to complex and fast-changing contexts: Using action learning methodologies to examine responses to supporting people with complex needs during Covid-19 and implications for future practice There is a growing recognition within public and third sector organisations that outcomes-based commissioning and management ignores the complexity (at an individual, organisational and systems level) in which services operate. Some in the sector are experimenting with more developmental, collaborative, place-based approaches. However strategic development has recently been disrupted by Covid-19, which has forced services to change overnight whilst increasing support needs within communities.

This project will analyse the ways in which community organisations have evolved during the crisis, and identify implications for future practice, not only in terms of service delivery models but also change processes and evaluation methods.

CoLab is a cross-sector ‘wellbeing hub’ hosting 30 organisations from community, social enterprise and public sectors supporting people with complex needs (e.g. homelessness, mental ill-health). As an embedded researcher I will work with staff and users as co-researchers, drawing on research tools from different methodological approaches (e.g. participatory action research, ethnography, developmental evaluation) to explore their experiences of using, delivering and adapting services in a rapidly changing context.

Key goals include producing recommendations for service development, identifying appropriate research methods to sustain an ‘action research’ culture moving forward, and sharing learning more widely within the sector and related academic fields.


WT/POST Fellowship

Scottish Public Health in the National Library of Scotland’s Moving Image Archives  Initiatives such as ‘The NHS at 70’ show strong public interest in the histories of public health in the UK. Such discussions have particular resonances in Scotland with the country’s reputation for poor public health and devolved responsibilities for healthcare. During my secondment, I will research the representation of hospitals, institutions of care and healthcare professions in Scotland, as found in the National Library of Scotland’s Moving Image Archive. The collections include documentaries, promotional and public information films, amateur works and newsreels, from the 1890s to the present day. My project will involve researching, contextualising and connecting key recordings to create appropriate narratives about public health in Scotland. I will research the histories and legacies of key Scottish institutions represented in the archive (such as East Fortune Sanatorium for tuberculosis patients, the innovative ‘therapy communities’ at Dingleton Hospital and ‘modern’ institutions such as Glasgow’s Stobie Hospital), situating this within a larger context of changing attitudes and policy about health and healthcare professions. I will create a curated interactive package, including clips and additional written information, for display at the Kelvin Hall premises.


International Masters Fellowship

International Livestock Research Institute, Kenya

Antimicrobial Resistant Enterobacteriaceae: Dairy production systems as potential sources of infection for humans in Kenya Antimicrobial resistance (AMR) is a global health threat, associated with increased morbidity, mortality, and financial costs.  Identifying the potential reservoirs of antibiotic resistance and resistance mechanisms is an important task to tackle AMR.  Klebsiella pneumoniae and Escherichia coli which can cause severe and often fatal infections such as septicemia and pneumonia are among the identified priority antimicrobial-resistant pathogens by the World Health Organization in 2017. Cephalosporins and Carbapenems are considered critically important antibiotics in the treatment of Gram-negative infections however their resistance has been reported in clinical settings.
The contribution of livestock as potential reservoirs and source of resistance genes to humans, which can be acquired by direct contact or through the environment and food-chain in Kenya is not known.
This study will investigate antibiotic usage, knowledge and practices amongst farmers and levels of AMR in different cattle dairy production systems to give an insight to Antimicrobial Usage and AMR, in particular focusing on the carriage of Cephalosporins and Carbapenem-resistant  Enterobacteriaceae (E. coli and K. pneumoniae). Moreover, we will investigate the genetic determinants conferring resistance and mobile genetic elements harboring resistant genes. Additional information on AMR would aid further research focused on combating AMR in developing countries.


WT/POST Fellowship

A life course approach to measure thriving places The overarching aim of this project is to provide theoretical and measurement expertise in the economics of health and wellbeing into the work of a UK-based charity, Centre for Thriving Places, and specifically, their Thriving Places Index (TPI). More specifically, this project will be developing a better understanding of the key indicators that influence the wellbeing of individuals at different stages of the life course. Currently the TPI is summarised at the local authority level in England and Wales and is arranged into three headline elements: Local Conditions for wellbeing, Equality and Sustainability. This project will seek to inform how reflective TPI is of different population groups wellbeing at different stages of the life course, looking at wellbeing in younger and older population groups in particular. Specifically, this research project will focus of wellbeing at different stages of the lifecourse based on the indicators that feed into the TPI. The Centre for Thriving Places would use the work from this secondment to better inform local authority decision-making targeted as specific populations in their community. For instance, different public health policy responses may be required depending on the age profile of diverse local authority populations.


Mismatches in Poverty Indices Over Time

WT/POST Fellowship

Mismatches in Poverty Indices Over Time Alternative indices of poverty may classify different individuals as being ‘poor’; these mismatches are problematic for charities and policy makers who aim to identify and reduce poverty. I will compare mismatches in poverty indices by considering distributional changes over time amongst different groups in the population. The analysis follows from Meyer and Sullivan (2008), who identify changes over time in consumption and income poverty in the USA. I will extend their analysis to the development context; using the Uganda National Panel Survey dataset (n≈3,000) multiple poverty measures will be constructed at the household-level, across the period 2009-2016. By focusing on distributional changes over time, mismatches between these measures can be identified, providing insights for policy makers trying to identify poverty trends. By disaggregating these measures a more in-depth analysis on the attributes of well-being, rather than aggregate summary statistics, will be conducted. Utilising a panel structure to follow individual households over time will allow for insights into potential causes of declines in well-being and the consequences of volatility. The paper will provide a methodological contribution to poverty analysis in the developing world, and offer policy relevant analysis of poverty in Uganda.

Keywords: Poverty Mismatches, Development Economics, Distributional Effects


International Masters Fellowship

A pilot study of a culturally appropriate hospital-based pulmonary rehabilitation programme among adults with functionally limiting chronic respiratory diseases in Malawi Malawi suffers a substantial burden of chronic respiratory diseases (CRDs) which causes significant morbidity and loss of economic productivity, and affects patients, families and health systems alike. CRDs are a major risk factor for Coronavirus Disease 2019 (COVID-19). Pharmacotherapy for CRDs is of limited benefit and costly. Its rational use could be complemented by non-pharmacologic treatments. For chronic obstructive pulmonary disease, pulmonary rehabilitation (PR) is well established as highly effective intervention which improves symptoms, quality of life and survival. PR is comprehensive package of interventions including exercise training. PR is now sufficiently understood to obviate further randomized trials in High Income Countries (HICs). However, given the design and delivery of programmes should be adapted to patient groups and context, high-quality data are needed outside HICs. My pilot study will determine feasibility and acceptability of PR in Malawi. Specifically, I will: (1) co-design, with service users and stakeholders, a locally appropriate PR program for patients with functionally limiting CRDs in Malawi, (2) examine lung function, exercise capacity and health status of participants before and after their participation in a PR program, and (3) examine participants’ levels of attendance, participation and adherence to the programme.

Keywords: chronic respiratory diseases, pulmonary rehabilitation, Malawi


WT/POST Fellowship

London as a Fast Track City: ending HIV by 2030 Fast Track Cities (FTC) is a multi-partner initiative aimed at addressing the challenge that cities bear a large share of the global HIV burden. London signed up to FTC in 2018 with the aim of eliminating HIV from the capital by 2030. The Healthy London Partnership (HLP) is the delivering organisation for London, bringing together representatives from Public Health England, NHS England, the Mayor of London and the London Councils. The aim of this fellowship is to work closely with HLP and support translation of the global goals of the FTC programme into the local context of London-specific initiatives, which include: funding and facilitating a quality improvement collaborative to increase HIV testing, access to HIV care and support for people living with HIV; and developing strategies to end HIV-related stigma. This project builds on my HIV social science research and on the extensive work on complexity in healthcare by our Oxford team, including current Medical Research Council and Wellcome Trust funded projects on context and complexity in health interventions. I plan to increase synergy between methodological research (Oxford) and gain experience of the translation of city-wide HIV policies and interventions through to implementation activities (HLP), with benefits to both partners.


WT/POST Fellowship

Ethics, youth mental health, and infectious disease outbreaks  To control the spread of the 2019 coronavirus disease (COVID-19) outbreak governments around the world have introduced public health measures including social distancing, isolation, and quarantine. This has created conflicts between competing ethical values, particularly protecting the publics’ health and safety v. respecting individuals’ liberty and preferences.

Concerns have been raised about the impact of currently-implemented measures on people’s mental health. Children and young people may be affected in unique ways, due to their younger age and specific role in society. Yet, their mental health needs may be easily overlooked when professional care is devoted to those who are in most immediate need, i.e. the immunocompromised and the elderly.

The aim of this project is to conduct a systematic review of the evidence on the impact of social distancing, isolation, and quarantine on young people’s mental health and wellbeing, and to interpret it in light of the ethics literature on public health emergencies. This work will be used to develop a UNICEF working paper focused on ethically-robust policy recommendations, so that public health measures that will be implemented in future infectious disease outbreaks are mindful of children’s mental health needs.

Children, young people, COVID-19, mental health, ethics, UNICEF, systematic review