- Total grants
- Total funders
- Total recipients
- Earliest award date
- 17 Oct 2005
- Latest award date
- 11 Jun 2019
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
The Global Climate and Health Forum is a one-day, high-level convening of global climate and health leaders designed to mobilize stronger health sector engagement in and commitments to climate action. The Forum will bring together 250 leaders from national and local governments, health systems, public health agencies, civil society, and international organizations to build the community of climate and health professionals, strengthen collaboration across sectors, and raise the health voice for climate action. The Forum will be held at the University of California, San Francisco on September 12th, 2018. The Forum is an affiliate event of the Global Climate Action Summit, and co-hosted by the UCSF Global Health Group, Health Care Without Harm, Global Climate and Health Alliance, and US Climate and Health Alliance. In order to make the Forum a truly global event, it is imperative that the Forum includes speakers and participants from low- and middle-income countries who are leading climate mitigation, adaptation, and resilience work in the most vulnerable regions and communities. Funding from the Wellcome Trust will be used to support five travel scholarships for participants from the global South, including all registration, travel, accommodation, and event-related expenses.
The Alliance for Accelerating Excellence in Science in Africa (AESA), Wellcome Trust (WT) and the Institut Pasteur International Network propose a researcher mobility program which would support African researchers (who share our ambition) to break down language and cultural barriers that impede greater African research collaboration in the biomedical and health sciences.Over the next 5 years, we aim to support at least 50 researchers to undertake mobility favoring the enhancement of their scientific careers while also increasing the understanding and interconnections of the African research community within different cultural and linguistic environments. Where language is the barrier we will look for flexible ways of providing support and funding language training. The program will aim to; Strengthen scientific collaboration between Anglo and Francophone speaking African scientists Build language skills/capabilities in English and French among African scientists Improve cultural understanding between English and French speaking African scientists The program will build out from the DELTAS and H3Africa researcher communities and the Institut Pasteur network, Our indicator of success will be; By December 2020, 50 African researchers will have experienced the mobility program and report positively on breaking down language and cultural barriers to research.
Metagenomic approaches are generating a long list of health and disease states associated with the microbiome (the microbes inhabiting our digestive tract) but without mechanistic understanding. The challenges arise from the enormous complexity of the microbiome, including genetic, environmental and dietary variations, microbe-microbe interactions, and the cost associated with studying the microbiome using murine models. If the field is to move beyond association, simple, well-controlled and cost-effective models allowing unbiased high-throughput studies are needed. The nematode C. elegans is a genetically tractable model, ideally suited for mechanistic and causative studies of host-microbiome and microbe-microbe interactions shaping host physiology and metabolism. Aims: 1) Establish an experimental microbiome in C. elegans based on strains from the human microbiome associated with health, disease and ageing 2) Generate fluorescent labelled bacterial strains and perform real-time imaging of gut colonisation 3) Characterise the effects of the experimental microbiome on the microbiome-gut-brain axis during ageing The experimental microbiome in C. elegans will be an important contribution to the field, complementing existing models. It will allow me to establish important collaborations, form a basis for my future research and address one of the most important questions of modern biology: the effects of the microbiome on host physiology.
The concept of cellular brain repair for Parkinson's disease is relatively simple - if brain cells die in this condition, then it should be possible to replace these cells through transplantation of healthy cells back into the brain. Over the past three decades, numerous animal studies and several clinical trials in human patients have shown that this concept has significant potential for repairing the brain affected by Parkinson's disease. However, poor survival of the healthy cells has limited the widespread roll-out of this cellular reparative approach to patients. Biomaterials, that is, materials that have been engineered to interact safety with living tissue for therapeutic purposes, have the potential to improve such cellular reparative therapies for Parkinson's disease. Specifically, injectable biomaterials gels have the potential to significantly improve cell survival by providing a physical scaffold and pro-survival environment for the implanted cells. Thus the aim of this proposal is to determine if biomaterial hydrogels can be used to improve cellular reparative therapies for Parkinson’s disease using animal models of the condition. We will specifically investigate the beneficial effect of biomaterials on stem cell-derived neuron cell transplantation approaches.
Optimising antimalarial treatments in sub-Saharan African children: reducing the burden of malaria mortality 31 May 2018
Sub-Saharan Africa accounts for 99% of all reported malaria cases. Children under five years are often the most vulnerable, accounting for 71% of all malaria deaths (WHO, 2017). This can be attributed to the low immunity in children which increases their vulnerability to malaria infections. Testing of drugs in children can be difficult due to ethical concerns. However, advances in pharmacokinetics (the study of how the body processes drugs) has given rise to a novel approach, which enables the simulation (in virtual clinical trials) of many clinical subjects, each possessing a unique subset of physiological parameters. Results from a previous research on pregnant women conducted by our group using the same approach was found to provide an effective dosage regimen (Olafuyi et al, 2017). In this project, we will adapt the pharmacokinetic approach to examine dosage regimen in children using piperaquine (antimalarial drug). We will also address potential drug interactions in patients co-infected with HIV, where anti-retroviral drugs can lead to the enhanced degradation of piperaquine. The study will look at data and its impact on cohorts and recommend an appropriate dosage regimen for children in sub-Saharan Africa under malarial only and malaria-HIV co-infection, which will help reduce anti-malarial resistance.
The main aim of our research is to determine the differences in the lifespan and physiology of male and female Drosophila melanogaster in response to increased levels of sugar (sucrose) in the diet. Current human diets are detrimental to health and obesogenic. The health outcomes are dependent on the sex of the individual, however the molecular and physiological mechanisms are not understood. The results of our study will help establish a Drosophila model that can be used to understand how nutrition and sex interact, which might contribute to a healthier lifestyle choices in humans leading to healthy ageing. The effects of diet on lifespan and diet-induced obesity of the two sexes will be recorded, as well as the feeding behaviour using the proboscis extension assay and blue-food assay. Gut morphology/function will also be examined since the gut appears to underlie the different response of the sexes to increased dietary protein. In particular, we will focus on age-induced hyperplasia by determining the number of proliferating cells (stained with anti-phospho-Histone 3). We will also monitor gut function by assessing the leakiness of the gut using a blue food. Finally, statistical analysis using suitable regression models will be performed in R.
PhD Grant Proposal 30 Sep 2018
Older people are often classed as either experiencing ‘normal’ cognitive ageing, or ‘pathological’ cognitive ageing as a result of diseases such as Alzheimer’s (AD). However, these classifications fail to reflect the spectrum of cognitive decline that is experienced as we age. Age-related cognitive decline is a hugely important health problem; it has a profound impact on quality of life, increases the risk of depression and may herald dementia. Because of this, it is important to investigate what influences how well we age cognitively. Age itself is the biggest risk factor for cognitive decline. The comprehensive causes and mechanisms of ageing are not fully understood but we do know that the process is closely integrated with inflammation – the body’s immune response to injury or irritants. Although recently receiving significant attention, the precise cause-and-effect relationship between inflammation and cognitive ageing has not yet been fully explored. Using different techniques, this project will investigate the role of inflammation in cognitive ageing, and whether the process can explain why some people are more resilient than others. Understanding the differences in individual’s cognitive decline is critical to developing interventions to prolong cognitive health and to gain insight into diseases of cognition such as AD.
Investigating the immunomodulatory effects of extracellular vesicles derived from mesechymal stromal cells 31 May 2018
My proposed hosting group has shown that mesenchymal stromal cells (MSCs) ameliorate kidney injury in mice through paracrine effects.Their preliminary work suggests that the MSCs are entrapped in the lung following intravenous administration and mostly die within 24 hours. Host macrophages are attracted to the MSCs and are stimulated to upregulate the anti-inflammatory cytokine, IL10, which suggests they are being polarised towards an anti-inflammatory phenotype (i.e. to M2 macrophages). The main aim of my project is to explore whether extracellular vesicles (EVs) released by the MSCs are responsible for mediating their immunomodulatory effects. Specifically, I will investigate whether the EVs polarise macrophages towards an M2 phenotype. The first objective will be to use a co-culture model comprising human bone marrow-derived mesenchymal stromal cells (BM-MSCs), which have already been shown to polarise macrophages to an M2 phenotype. The BM-MSCs will be co-cultured with human macrophages using a transwell culture system, and the ability of the BM-MSCs to polarise the macrophages to M2 will be investigated using flow cytometry and quantitative reverse transcriptase PCR (qRT-PCR) to determine the levels of M1 and M2-specific markers. The effect of BM-MSC-derived EVs on macrophage polarisation will then be tested.
Dynamical modelling of somatic genomes 28 Nov 2017
Cancers are complex and chaotic systems. It is becoming apparent that no two cells in a cancer are genetically identical or follow the same evolutionary trajectory. Chromosomal instability (CIN) is one way that cells generate this complexity and is a hallmark of all cancer and ageing. In cancer, it increases the level of variation available to cells and gives rise to intra-tumour genetic hetereogeneity, which makes the disease more agressive, drug tolerant, and harder to treat. We are still far from a complete understanding of how cells undergoing CIN evolve over time, in particular, we do not know how populations of cancer cells evolve and how selection acts to change these properties. Understanding this normal evolutionary behaviour will be key to separating the functional and non-functional aspects of intra-tumour heterogeneity. We will tackle this problem by understanding cancer as an emergent complex system, and use simple dynamic stochastic models to capture the essential biological features of the processes underlying CIN, including chromosome gain and loss, structural change, and genome doubling. We will use the vast amount of NGS data already available to fit these models using Bayesian inference and infer the evolutionary aspects of CIN in healthy and cancerous tissues.
Diagnostic needs for Antimicrobial Resistance 30 Sep 2018
Despite various calls for action and some initial work to map diagnostics for AMR, no authoritative list exist for commercially available (or under development) in vitro diagnostics for antimicrobial resistance (AMR in vitro diagnostics). Similarly, Target Product Profiles to guide the development of these diagnostics are also lacking. Multiple stakeholders including the diagnostic industry, academia and NGOs have stressed the need to address this gap. In response to this scenario, WHO will coordinate the mapping of diagnostic tools (both existing and in development) to address antimicrobial resistance; identify gaps and establish a WHO R & D priority list for AMR in vitro diagnostics. Target Product Profiles for high priority AMR in vitro diagnostics will also be developed, published and disseminated to relevant stakeholders.
The hypothalamus governs homeostasis of core body function throughout life but its development remains enigmatic. Our recent unpublished work reveals that a small region at the ventral midline of the embryonic neural tube intrinsically develops into the three classically defined domains of the adult basal hypothalamus, including a domain that contains stem cells. This suggests an unprecedented mechanism of self-organisation exists within ventral midline hypothalamic progenitor cells that we will define in this application. Our objectives are to: 1. Identify when self-organising hypothalamic progenitors are induced, and the tissues required 2. Determine the minimum cell number that can self-organise into the hypothalamus 3. Understand if self-organisation involves a self-renewing multipotent stem cell 4. Characterise cell behaviour in self-organising hypothalamic progenitor cells 5. Understand the molecular basis of hypothalamic self-organisation These studies will reveal mechanisms that orchestrate hypothalamic development. They will provide insight into the extent to which hypothalamic stem/progenitor cells can adapt over time and generate/regenerate new cell types. Finally, they may provide insight into the construction of hypothalamic organoids, an important future tool to understand the function and sensitivity of this small, intricate and hard-to-access region of the brain.
Pseudomonas aeruginosa is a Gram-negative bacterium that is a leading cause of many hospital borne infections. In particular recent research has identified the Type 6 Secretion System (T6SS) present in P. aeruginosa and has focused on the structure and mechanism of the system. This highly complex system allows P. aeruginosa to accurately penetrate adjacent cells and thus insert an array of toxins which can cause cell death or disrupt cellular pathways. Building on this work we would like to understand the T6SS from a statistical perspective. Understanding the spatial distribution and dynamics of the T6SS along the cell membrane of P. aeruginosa are amongst a number of different questions we hope to explore in this project. To achieve these targets we will use fluorescently tagged components of the T6SS mechanism as well as confocal microscopy of living P. aeruginosa, thus allowing for 3-dimensional reconstruction. These biological questions will be answered using a variaty of quantitative approaches. To extract important information from the image data a number of imaging and video preprocessing methods will need to be applied. After preprocessing the this data will be analysed using a variaty of statistical methdologies in order to provide a quantitative description.
Active Inference and Optimal Decision-Making 30 Sep 2018
Depression is strongly associated with a decline in cognitive function, and is seen in a high number of elderly individuals. It has been suggested that there is a strong epidemiological link between a personal history of depression and an increased risk of developing Alzheimer’s disease in later life. The key aim of this project is to use models of learning and decision-making to better link behavioural characteristics of these two psychiatric illnesses to their brain circuit substrates. We aim to reveal model-based behaviours and brain circuits that are shared with depression and different dementia profiles, including Alzheimer’s disease. We will use an adapted version of a pre-existing video game environment to examine activation of the dopaminergic midbrain, using fMRI. We will look specifically at reward prediction errors, and precision, i.e. the degree of confidence in the action an individual takes. By describing these behaviours using computational models, we hope to provide more accurate descriptions of human behaviour, the causes of such behaviours, and the specific brain regions and neural circuits that these behaviours are linked to. This may lead to earlier diagnosis of such psychiatric illnesses; therefore patients can undergo treatments earlier on in the disease progression.
We are applying for two Wellcome Fellowships on the Clore Leadership Programme, to join cohorts of exceptional cultural leaders who can engage and stimulate new thinking and development across a wide range of audiences and sectors, including health, research and wellbeing by combining perspectives from the arts, humanities and social and medical sciences. The final focus of the Fellowships will be determined in discussion with the Wellcome Trust and in line with its priorities. The Fellowship is a bespoke professional development opportunity responding directly to the training needs of the individual, which includes residential courses, coaching, mentoring, a secondment, and access to a personal training budget. Our ambition is to support professional development and create resilient and authentic leaders, who can support their peers and the sector, and can ensure that the arts and culture are having the most positive possible impact on civic life. By offering the Wellcome Fellowships in 2019/20 and 2020/21, we aim to support the development of leaders who will encourage their audiences, collaborators and the wider public to access research and innovation, and establish better dialogues between the public and the scientific community through culture.
Investigation into the role of RBM8A/Y14 in the development and function of megakaryocytes and platelets using a human pluripotent stem cell model of haematopoiesis 30 Sep 2018
Platelets are small blood cells, which cause blood to clot, preventing bleeding after injury. They are produced by megakaryocytes, large cells in the bone marrow. In people with low platelet counts (thrombocytopenia), life-threatening bleeding occurs spontaneously or after injury. Studying platelet and megakaryocyte development and function is important in understanding a) diseases causing thrombocytopenia, such as genetic disorders and other conditions, particularly cancer (and chemotherapy) and b) strokes and heart attacks, where platelets are excessively activated, forming clots that block vessels. Using stem cells (special cells capable of becoming any cell type) derived from adult skin or blood samples we grow & study megakaryocytes and platelets in the laboratory. We study a rare genetic disease, Thrombocytopenia with Absent Radii (TAR) syndrome, in which babies are born with very few platelets and abnormal bone formation (particularly the radius in the forearm). Our group discovered the cause of TAR, due to abnormalities in a gene called RBM8A, which helps cells control what proteins are produced; however precisely why this causes TAR is unclear. We believe our research will uncover the mechanism of this condition, helping to treat patients with TAR and improve wider understanding of how megakaryocytes & platelets develop and function.
Understanding how the billions of varied cells in the human brain develop from a small number of neural stem cells (NSCs) is a central question in biology and medicine. This highly complex process has largely been explained by transcriptional regulation dictating the levels of protein expression in stem cells and their progeny. Using novel single molecule approaches to quantitate transcription and protein levels, we have discovered functionally important conserved examples where the levels of transcription and protein expression do not correlate. These include pros/prox1, the regulator of NSC proliferation and differentiation and myc, the proto-oncogene regulator of stem cell size. We will characterise the mechanism of post-transcriptional regulation of pros, myc and 21 additional functionally important examples we have discovered, all of which have extremely long 3’UTRs that are bound and regulated by the same conserved RNA binding proteins, Syp and Imp. We will also measure, genome-wide, mRNA stability and characterise the trans-acting factors and cis-acting signals regulating stability and translation. The proposed programme will characterise a hitherto under-studied layer of regulation acting in addition to transcription in complex tissues, providing major new mechanistic insights into how the brain develops in health and disease.
My aim is to complete a quantitative analysis of the dynamic signalling pathways that control mitosis. By combining mass spectrometry with cutting-edge microsopy I intend to measure the number of active molecules of the key mitotic regulators and determine how and where they interact to generate a highly responsive signal transduction network that ensures genomic stability by controlling sister chromatid separation and mitotic exit. I have four main aims: 1) Measure the numbers of the mitotic regulators controlling chromosome separation and analyse how they are modulated by post-translational modifications (PTMs). 2) Determine the dynamics of the spindle assembly checkpoint (SAC) in living cells by measuring the generation of the SAC effector complex and the flux of its components through the pathway. 3) Determine how changes to a kinetochore affect its ability to catalyse the generation of the MCC. 4) Determine how a defined change in the number of molecules of specific regulators alters the dynamics and strength of the SAC, and in consequence their effect on genomic stability. Together, these studies will be used to inform and discriminate between models of mitotic control to determine how the SAC combines the properties of potency and responsiveness.
The Royal College of Psychiatrists has been proud to partner with The Wellcome Trust on a co-funded project with the Gatsby Foundation between 2016 and 2018 through the first phase of this project. The ‘Integrating Neuroscience’ project has achieved significant success under the leadership of the President of the RC Psych, guided by an internationally-renowned Neuroscience Commission which was established as a result of this partnership. The project continues to achieve the intended outcomes within budget and on time. Following discussions with both The Gatsby Foundation and The Wellcome Trust, we propose the renewal of this partnership for a further three years. The changes we would like to see as a result of this next phase are: That the sustainability of the project is ensured so that it becomes part of core College business with a curriculum lead funded by the RC Psych. That the recommended changes to the psychiatric curriculum will have been implemented and tested. That we will have secured external funding to assess the impact of these changes. That we will have built a community of neuroscientists and neuro-psychiatrists who will curate the knowledge base and drive collaboration across the whole sector.
Dissecting Androgen excess and metabolic dysfunction – an Integrated SYstems approach to PolyCystic Ovary Syndrome (DAISY-PCOS) 28 Nov 2017
Polycystic ovary syndrome (PCOS) affects 5-10% of all women; androgen excess is one of its major diagnostic features. While often perceived as a reproductive disorder, PCOS is now emerging as a lifelong, complex metabolic disorder, with increased risk of type 2 diabetes, hypertension, cardiovascular disease, and, as recently documented, non-alcoholic fatty liver disease (NAFLD). However, there has been no recent breakthrough regarding risk stratification or therapeutic intervention in PCOS. Our work has provided evidence for a key role of androgens in the development of PCOS-related metabolic complications. We will combine cutting edge in vivo physiology techniques, state-of-the-art metabolomics and machine learning-based computational approaches to address our overarching hypothesis that androgens are major drivers of metabolic risk in PCOS. We will use an integrated set of in vitro, ex vivo and in vivo experimental medicine studies to test this hypothesis and answer our specific questions: Does the control of androgen excess improve metabolic function? What is the role of different androgen pathways in conveying metabolic risk? Can we integrate phenome and metabolome data by machine learning to predict metabolic risk in PCOS? Our overall aim is the identification of novel personalized approaches and therapeutic targets for patients with PCOS.