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The Wellcome Trust


Homeostatic gene networks in Drosophila models of epilepsy and dyskinesia 31 Jan 2017

Transcriptional and translation control in neurons is highly plastic, allowing firing frequency and synaptic output to be regulated with high temporal precision. Recent research has demonstrated that the complement of ion channels within a neuron can undergo homeostatic remodelling in response to altered neuronal excitability. However, the extent to which this occurs in neurological diseases is unknown, as are the alterations in ion channel expression that may buffer disease-linked mutations to the greatest degree. We aim to investigate these questions using the fruit fly, Drosophila melanogaster. Using homologous recombination, we will generate a novel knock-in fly model of Generalized Epilepsy and Paroxysmal Dyskinesia (GEPD). This disorder is caused by a gain-of-function mutation in the KCNMA1 BK potassium channel – the mammalian homologue of Drosophila slowpoke (slo). We will characterise changes in ion channel expression in GEPD slo knock-in flies through RNAseq, and using this data, perform a modifier screen to determine which alterations are compensatory or pathogenic. Genetic suppressors identified via this strategy will represent promising targets for future therapeutic interventions.

Amount: £0
Funder: The Wellcome Trust
Recipient: University College London

How do cells integrate signals? Roles of timing in neural induction 31 Jan 2017

During embryonic development cells have to integrate up to eight molecular pathways in order to choose between alternative fates or behaviours. However, even in combination, these eight pathways cannot provide enough information to specify the many (perhaps as many as 104) cell types that comprise the adult body. Timing seems to be important. One of the earliest fate decisions in embryonic development occurs soon after gastrulation during neural induction when one part of the epiblast is set apart, acquiring neural identity in response to signals from the organiser, Hensen’s node. A recent view is that neural induction is highly regulated in time and that it involves several steps. Competent cells, capable of responding to signals from the organiser, go through different states of specification before committing to the neural fate. Here we aim to understand how timing orchestrates neural induction. Specifically, we will uncover whether competence to respond to inducing signals is regulated by a cell-autonomous clock or by external instructions, how competent cells can sense exposure to signals of different duration and how this signal changes over time to generate an appropriately regionalised neural plate.

Amount: £12,700
Funder: The Wellcome Trust
Recipient: University College London

‘Pre-embryos’ Revisited: a historical sociology of translational biology 02 May 2017

This project will revisit the debates on human fertilisation and embryology that took place after the release of the Warnock report in 1984 and ended with the enactment of the Human fertilisation and Embryology Act in 1990. Firstly, it will ask how developmental biologist Dame Anne McLaren (1927-2007) used the scientific concept of the ‘pre-embryo’ as a rhetorical device in the debates to make the case for the continuation of research. McLaren’s role as the only research scientist on the Warnock Committee, but also in public debate and in the scientific community offers insight into the translational dimensions of human embryo research. Secondly, the research will explore the legacy of the term ‘pre-embryo’ by asking practicing developmental biologists conducting research that begs for an extended limit on in vitro research on human embryos, to reflect on the term in order to suggest which lessons about biological translation can be taken from the debates in the 1980s, and to assess the usefulness of new scientific terms and concepts when engaging lay-audiences in scientific debates.

Amount: £135,903
Funder: The Wellcome Trust
Recipient: University of Cambridge

Water, health, and kidney disease in Sri Lanka: perspectives from anthropology and chemistry 02 May 2017

The proposed project combines theories and methods from the anthropology of science, environment, and health and water chemistry, with the overall aim of contributing towards academic and policy research on health and environmental crises produced by water pollution in the developing world. As a case study, project will explore the epidemic of Chronic Kidney Disease unknown etiology (CKDu) in Sri Lanka. It will focus on how scientific, medical and policy narratives of the disease have come to center on water, accompanied with a study of ethno-chemical understanding versus chemical quality of water. It will further investigates different forms that water take when approached by scientific and medical community and a community severely affected by CKDu. Specific objectives of the research would be, Explore the cultural and historical conditions surrounding water in relation with CKDu epidemic. Map the emergence of a lexicon around water Compare criteria used by scientists and ordinary villagers to judge water quality Develop maps of water quality as identified through scientific and ethno-chemical knowledge Understand how people’s lives in a CKDu-affected village with a particular reference to water Contribute towards scientific, advocacy and policy debates regarding CKDu and environment/water pollution

Amount: £128,520
Funder: The Wellcome Trust
Recipient: University of Durham

Utilising electronic health records and Mendelian randomisation to investigate the relationship between liver function biomarkers and gastrointestinal disease; an example of bilirubin 30 Sep 2017

Liver function tests (LFTs) are commonly performed in clinical practice and are often associated with malignant and inflammatory diseases. Bilirubin has an anti-oxidant, cytoprotective function, and reported inverse associations with conditions including cardiovascular disease, inflammatory bowel disease, colorectal cancer and overall mortality. We will use linked primary care, hospitalisation, disease registry and mortality data in England (the CALIBER programme), [1] and include people aged 18 or older with no underlying gastrointestinal disease at baseline. We will use Cox models to estimate cause-specific hazard ratios (HRs) for the association of baseline bilirubin with onset of gastrointestinal disease. We will further compare outcomes in gastrointestinal disease and malignancy cohorts including hospitalisation rates, relapse-free survival, net survival and mortality. Finally, we will determine whether the associations detected (with serum bilirubin) are likely to be causal by utilising a Mendelian randomisation approach.

Amount: £253,846
Funder: The Wellcome Trust
Recipient: University College London

Signalling pathways that control T cell metabolism and T cell fate 30 Nov 2016

The laboratory will map how antigen receptor, cytokine and environmental signals integrate to control the function of T lymphocytes. We will comprehensively define signaling pathways that maintain T cell metabolism, transcriptional and proteomic landscapes. Specifically, we will comprehensively delineate the molecular details of how changing the supply of oxygen, glucose and iron impact on T cell signal transduction pathways and T cell phenotype. We will explore the ability of the Prolyl hydroxylase domain protein PHD2 and the transcription factor NFIL3 to link oxygen sensing to the control of T cell function. We will define how glucose fueled signaling pathways including those mediated by AMP-activated Protein Kinase alpha1 (AMPKa1) and the O-GlcNAc transferase (OGT) control T cell fate. We will comprehensively map how the protein tyrosine phosphatases SHP-1 and SHP-2 regulate protein phosphorylation networks in T cells and how they modulate T cell proteomes and T cell function. We will also characterize signaling pathways mediated by Phosphatidylinositol 3,4,5-trisphosphate PI-3,4,5-P(3) and define how the lipid phosphatases PTEN and SHIP1 shape T cell metabolism and T cell function. These experiments will map and define the molecular processes that determine T cell fate outcomes.

Amount: £3,954,769
Funder: The Wellcome Trust
Recipient: University of Dundee

Role of ATP in Chronic Cough 11 Jul 2017

The cough reflex is triggered by ion channels present on vagal nerve termini which can be activated by a wide variety of irritants. Utilising a P2X3 antagonist we have identified ATP as a driver of chronic idiopathic cough which is treatment refractory. However, the mechanisms are not known and it is not clear whether similar efficacy will be observed in chronic cough associated with common respiratory diseases. We have identified different neurophenotypes in patients with chronic cough associated with different lung diseases suggesting that a single therapeutic may not address cough across all indications and that mechanistic information will be required. Furthermore, upstream targets, involved in the release of ATP, may provide a broader efficacy profile as ATP has been shown to have a range of disease relevant biological effects in the lung mediated by purinoceptors. We will identify (1) whether ATP is a biomarker of treament sensitivity; (2) upstream targets involved in the release of ATP; (3) the contribution of the upper airway to ATP-induced sensations; (4) the role of ATP in mediating chronic cough across other airway diseases? This project will identify novel targets, biomarkers and the patient phenotypes that will respond to treatment.

Amount: £166,005
Funder: The Wellcome Trust
Recipient: University of Manchester

The MYRIAD Project: Exploring Mindfulness and Resilience in Adolescence 30 Jun 2017

The MYRIAD Project: Exploring Mindfulness and Resilience in Adolescence

Amount: £250,800
Funder: The Wellcome Trust
Recipient: University of Oxford
Amount: £150,535
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Wellcome Trust Engagement Fellowship 20 Jul 2017

Science and the arts overlap as both are means of exploration, investigation and creativity. Both share an interest enhancing human understanding and extending experience to the world. Often, indigenous knowledge systems have been excluded or played a minimal role in this dialogue and within engagement practices. I am interested in exploring and implementing projects that focus on collaboration and co-creation across these fields. I believe that inclusive collaborations, partnerships and co-design between these fields have the potential to enhance livelihoods by making science more accessible and relatable, spark innovation and creativity, and challenge existing biomedical engagement practices. I wish to explore, test and refine methods and products that incorporate community- and culturally-sensitive methodologies i.e. art forms that communities are already familiar with and receptive to. These partnerships between science, arts and community development will encourage innovation and participation. I envision that projects adopting this approach would challenge and enrich all participating parties, stimulate dialogue, facilitate exchange and allow all parties to play active roles in decision-making. Traditionally, science communication and public engagement projects tend to merely inform participants of scientific processes which is non-participatory, devaluing and potentially exploitative. I will explore partnerships that use a definition of participation that is much more robust: co-design and collaboration. I believe that each group has specific, viable and valuable skill sets and knowledge, which collectively are powerful and necessary within the context of engagement. I also wish to explore ways in which science can be more accessible and relevant to the public and vice versa. I hypothesize that these bodies of knowledge, collectively, have the capacity to enhance or transform lives, engagement and community interventions as: 1.Formal scientific knowledge is highly specialized and could empower and relay knowledge to communities, which are often excluded; 2. Community-based practices and knowledge can situate illness and health within specific community dynamics and; 3. Art has the capacity to relay key messaging in a culturally-relevant, community-sensitive means to ensure relativity, inclusion, participation and ownership. I would like to explore how collaborative project co-design: impacts on community members', artists’ and scientists' internalization of information; can be used as a collaborative communication strategy and; challenges traditional methods public engagement. This process calls for all participating parties to reflect on their own practice, innovate and test alternative methods, and interact with each other. I would like to explore arts in various forms, especially street arts which should be understood as visual or performance based art that is presented in untraditional arts venues and locations, i.e. on the streets or within communities. I am particularly interested in street arts as it is dynamic and accessible to many different audiences, and has served as an active and effective communication and advocacy medium that is entertaining, empowering and controversial. My vision for the future of science communication and public engagement is to strive for continuous and reflective innovation to ensure the accessibility of science to wider groups, leading to greater inclusion, empowerment and education.

Amount: £148,027
Funder: The Wellcome Trust
Recipient: No Organisation

Marked (Working Title) 07 Sep 2017

Marked, will be an experimental art film, an adult-oriented cartoon hoping to create a greater awareness and acceptance of the psychological impact of disfigurement, post-surgical trauma: with particular reference to the wearing of mastectomy tattoos by people with breast cancer. Featuring Alicia, who, after undergoing mastectomy surgery, declines breast reconstruction but instead decorated her scars with a tattoo. The fantastical, open-ended nature of cartoon animation itself allows Alicia to tell her story, to represent her very real, extreme, exaggerated states of being. Marked will ask/raise various complex questions and ideas about disfigurement body-image, symmetry, and subsequent post-surgical trauma: What role does symmetry play in our physical and psychological understanding of ourselves? What are the boundaries of both physical and psychological loss? What does it mean to live as a woman with a tattoo where her breasts once were? What happens to our identity/bodies after surgery? The visual manifestations of myths, folktales, personal narratives, ideas, desires and/or histories, the locations of the tattoos, the act of tattooing and the tattoos themselves are powerful responses to disfigurement that mark the sites of trauma, while marking the survival of breast cancer.

Amount: £198,900
Funder: The Wellcome Trust
Recipient: Royal College of Art

TELL ME WHO I AM 30 Jul 2017

Imagine waking up one day to discover that you have forgotten everything about your life. Your only link with the past, your only hope for the future, is your identical twin. Now imagine, years later, discovering that your twin had not told you the whole truth about your childhood, your family, and the forces that had shaped you. This has been Alex's reality: a world where memories are just the stories people tell you, where secrets are hiding around every corner. --- Based on a best-selling memoir, TELL ME WHO I AM is a documentary film from the Academy award-winning producer of SEARCHING FOR SUGAR MAN about identical twins Alex and Marcus Lewis. Combining interviews, archive and original footage, this film will take audiences on an extraordinary journey that reveals shocking betrayals, a secret tragedy and, above all, redemption founded on brotherly love. Touching upon themes such as trauma, mental health, and memory loss, the result is a voyage between the blurred boundaries of fact and fiction, memory and reality. A story that while often heartbreaking, is ultimately inspirational and life-affirming. TELL ME WHO I AM is about the bonds that allow us to survive. Trailer: password: TMWIA-sizzle-170203

Amount: £5,000
Funder: The Wellcome Trust
Recipient: Lightbox Media Ltd

SMASHfestUK: 2018/19 - consolidation application 30 Sep 2017

SMASHfestUK is at a critical juncture: Having established a successful family festival in Deptford, specifically engaging underserved audiences, we seek to consolidate learning, deepen, embed and extend our community engagement and develop sustainability plans. Our purpose is to increase STEAM engagement for people in Deptford and their families, ultimately leading to increase STEAM study/career choices, increased engagement with research and research outcomes, and increased biomedical knowledge. Increasing science and social capital will increase opportunities for young people in STEAM careers, thus increasing social mobility and future investment in the local Deptford economy. We seek to develop a business strategy for sustainability. A manager and community outreach team will be employed throughout 2018 and 2019 to underpin the development of community clubs and workshops, with outputs culminating in SMASHfestUK delivery. The manager will focus on diversifying our income portfolio: (we have 1 established commercial sponsor, Vound, and are negotiating with Air Products and Tideway, and are also developing a commercial arm) We will continue our community-embedded hyperlocal approach measuring science-capital outcomes, whilst continuing to build our interdisciplinary community of practice, by engendering intra and inter dialogues between publics and industry, and continuing to explore innovative methods and strategies for engagement.

Amount: £60,000
Funder: The Wellcome Trust
Recipient: Refinery Productions Ltd

Rare Disease Priority Setting Partnerships 30 Sep 2017

We will engage rare disease patients/carers and clinicians to identify their research priorities, in order to influence the research agenda in a way that benefits patients: we will use the established and esteemed James Lind Alliance model of Priority Setting Partnerships (PSPs), administering two PSPs for groups of related diseases. Selection of the disease areas will be made following consultation with our membership, ensuring that the project is democratic and is driven by motivated patient groups. Wellcome Trust funding will allow economies of scale through running two simultaneous PSPs, and will enable very small patient groups with restricted resources to participate. We will make the process as accessible as possible: for example, delivering surveys in accessible formats; and will facilitate the involvement of teenagers and young people. Our membership is highly motivated to take part in research - together with our own experience in steering two existing rare disease PSPs, and our policy and public affairs expertise, we are in a strong position to facilitate successful PSPs that will influence research funding and policy for the benefit of rare disease patients. By disseminating learning from the process we hope to support the establishment of further successful PSPs for rare diseases.

Amount: £60,000
Funder: The Wellcome Trust
Recipient: Genetic Alliance UK

Back to the Future 30 Sep 2017

As a leisure trust provider with strong links to underserved audiences, we can bring research into the hearts of communities in order to facilitate important conversations between those not accessing sciences, with those who have the power to direct future research to improve health. By hosting a series of 8 informal and relaxed workshops co-insided with existing activities provided through Life Leisure's exercise programmes, this project will encourage participant to go back to the future and discuss the evidence around physical activity and whether this was what partcipants thought would have happened, if they were to go back to their pre-exercised self. With limited use of science engagement within our programmes, this project will create a colloboration between both leisure and academia, which can pave the way for new models of working and cab be repliacted across both sectors.. In addition, by discussing with participants about their pre-exercise self, we hope to learn more about their attitudes and beliefs to exercise which will form a basis for future service improvements. Finally, we want to see whether engaging people with health related science can lead to greater upatke of participants to our services which can lead to improvements in their health.

Amount: £13,500
Funder: The Wellcome Trust
Recipient: Stockport Sports Trust

Bits - A new play exploring myths about the vulva 30 Jun 2017

We are applying for funding to develop Bits, a new play for 15-25 year old women exploring the myths, anxieties and confusions that surround the vulva. Women, particularly young women, are not talking about their bits. Sex education has only just been made compulsory in England and is yet to be made compulsory in Wales, Scotland and Northern Ireland. Athletes who talk about their periods, writers who write about their vaginas and actors who show their vulvas (real ones, with hair and bits that hang) are deemed radical. This stifling silence has become a breeding ground for confusion and unrealistic aspirations that could explain disturbing patterns in female behaviour such as the significant rise in requests for labiaplasty, particularly amongst adolescents. Using a cabaret style, Bits will feature singing and stand up with a story about a mother and a daughter at its heart. We will conduct interviews and collaborate with medical health professionals to create a truthful and inclusive play that asks: what is normal? What are you worried about? How can you change that? How did we get here? The project is being supported by The Yard Theatre, London and will culminate in a sharing in the autumn.

Amount: £8,000
Funder: The Wellcome Trust
Recipient: Papermash Theatre Limited

A Touch of Flu: Centenary of the Spanish Flu Pandemic 30 May 2017

Between the early summer of 1918 and the spring of 1919 the ‘Spanish’ influenza (so-called because Spain was the only country not to censor reports of the spreading epidemic) claimed the lives of a quarter of a million Britons. Worldwide, the death toll from the flu has been estimated at fifty million – ten times as many as died in the First World War and ten million more than AIDS has killed in thirty years. Timed for the centenary of the pandemic in 2018, this project is part of an exciting collaboration between the Florence Nightingale Museum, Queen Mary University of London and the Commonwealth War Graves Commission. ‘A Touch of Flu’ will combine public engagement with academic excellence and will bring together a touring exhibition, a digital resource and an animated short film.

Amount: £82,000
Funder: The Wellcome Trust
Recipient: Florence Nightingale Museum