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The Wellcome Trust

Results

A Cluster for the Development of Dynamic 3D Nanoscopy 05 Jul 2016

Imagine if we could watch multiple molecules in living cells as they move and interact. This dream may seem years away, but it is now realistic to achieve real-time dynamic super-resolution imaging of multiple tagged proteins in three dimensions (3D) in cells and in tissues. This will allow biologists to discover large-scale patterns involving diverse structures including transport vesicles, ribosomes, and chromatin domains, all previously inaccessible because they lie in the gap between the resolution of electron (1- 2 nm) and light microscopy (200-300 nm). The "big picture" of cellular organization/information processing would emerge, with advances in understanding cell function in health and disease. While we can now do this in 2D, 3D imaging is needed to follow objects as they move out of the plane. Achieving 3D imaging is a major challenge and will require two orders of magnitude more information per cellular volume, and novel algorithms to classify, analyze, and visualize patterns from massive datasets. We propose specific innovations (Table 1) that, should allow us to achieve this over the next five years, given our team’s proven track record of success.

Amount: £660,923
Funder: The Wellcome Trust
Recipient: University of Cambridge

New approaches to big data in genome sequencing 31 Jan 2017

The ever increasing throughput and reducing cost of DNA sequencing continue to challenge computational data analysis associated with genome sequencing, requiring novel algorithmic and software solutions that take advantage of structure in the data. We will develop new efficient computational solutions to handle and analyse very large genome sequence data sets. Specifically, we plan to develop software to address the following topics, in the context of the human Haplotype Reference Consortium with tens of thousands of whole human genome sequences, and also large non-human vertebrate reference genome sequencing projects. We will develop compressed data structures to store deep population resequencing data, while supporting fast genetic analyses that work directly from the compressed data. We will extend these methods to new reference structures based on variation graphs. We will develop new approaches to long range genome sequence assembly, using long reads to scaffold deep short read assemblies, and using linkage disequilibrium structure in population data to scaffold assemblies, incorporating methods from topic (1). We will use machine learning approaches to address statistical problems such as indel and structural variant calling that are hard to model exactly, using large simulated and real data sets and methods from (1) and (2).

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Cambridge

Wellcome Trust Engagement Fellowship 2012. 03 Oct 2015

The Wellcome Trust is widely recognised in the UK and internationally as the leading funder of innovative public engagement, inviting the public to explore big scientific challenges. Likewise, I have a reputation and passion for delivering innovative, high-quality public engagement across the interface of science, medicine and the humanities. Public engagement has an important role in achieving extraordinary improvements in human health and, as a pioneer who works with the public, including with some of the most deprived, yet creative communities in the UK, I can offer a considerable contribution to the Wellcome Trust Vision. Through my public engagement endeavours, I work responsively to cultural contexts and strive to forge trust in order to breakdown the barriers between researchers and the public. By way of example, my public engagement endeavours have connected non-English speaking communities at risk of disease and infection to work alongside researchers investigating associated biomedical diseases. These public engagement activities have transformed community members into advocates and translators of important health information. My experience and commitment to creativity, intellectual curiosity, professional development and organisational learning ensure I thrive as a Wellcome Trust Fellow. As a filmmaker and archive fanatic I was inspired by the Wellcome Library collection, with a game, Lost Cats Legacy, that caught the attention of Sheffield International Documentary Festival. I am excited by the public engagement possibilities of the digitised material from the Wellcome Library’s collection and the prospect of support from Wellcome staff to unlock its creative potential. A Wellcome Fellowship would present considerable strategic added value by helping me to consolidate lessons from ‘networked’ and citizen-led approach to public engagement that I am pursuing. Specifically I will offer an offering ongoing legacy to support the Trust’s Vision through audiences reached, quality of partnerships and heightened profile of biomedical science.

Amount: £826
Funder: The Wellcome Trust
Recipient: Squirrel Nation Limited

‘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

Big Tissue and Society 17 Jul 2017

‘Big Tissue’ marks a new era of biological innovation based on industrial production delivering a step-change in the quantities of bodily tissue engineered. This project analyses four case studies of significant upscale in human and animal tissue production: cultured blood, cultured skin, cultured meat, and biofabricated animal tissue. Collectively these case studies illuminate the complicated and contradictory ways Big Tissue will transform our sense of what we can do with the body. Qualitative methods (interviews, observations, documentary analysis) will inform a sociological and Science and Technology Studies (STS) perspective. Key analytical themes include commercialisation and value, human-animal relations, the sensory, and the ontological and ethical status of each case and the broader category of Big Tissue. The research will assess current practice and articulate future social science research agendas about human and animal health. Key goals: -Analyse the current ontological, ethical, commercial, and material context of Big Tissue through empirical analysis of four case studies. -Articulate the novel relationships invoked by Big Tissue and how the social science agenda must respond. -Deliver six papers, a monograph, significant public engagement, and contribute to policy at governmental and third sector level.

Amount: £261,297
Funder: The Wellcome Trust
Recipient: Brunel University

A dissection of the intercalated disk to stop sudden cardiac death 05 Sep 2017

Despite decades of research, every week in the UK, twelve individuals under 35 years of age die unexpectedly; a tragic event known as sudden cardiac death (SCD). I believe that a key to stopping SCD is elucidating what transpires at the intercalated disk (ID), the area of heart cell-cell mechanical and electrical coupling. We recently showed that a few proteins are redistributed from and to the ID in SCD, which has significantly improved diagnosis and management of surviving family members. The ID, however, was recently shown to contain >760 proteins, a number so vast that begs the question; is our work hitherto just the ‘’tip of the iceberg’’? I will employ a novel technology to isoalte the IDs from formalin-fixed samples and through cutting-edge proteomics resolve for the first time the full spectrum of protein remodelling in SCD-IDs due to two distinct, yet overlapping disease entities; arrhythmogenic cardiomyopathy and Brugada syndrome. This high-throughput screening of the ID will uncover novel diagnostic signatures, whose specificity I will evaluate using the world’s largest bank of SCD myocardial samples. Finally, decrypting the IDs’ molecular remodelling will lay the foundations for much-needed mechanism-targeted therapies, necessary to reduce the burden of SCD in our society.

Amount: £93,967
Funder: The Wellcome Trust
Recipient: St George's University of London

Taking treatment of chronic lifelong conditions to scale: applying the positive deviance approach to health programme management. 25 Mar 2014

In sub-Saharan Africa, and in South Africa in particular, there are significant numbers of people living with HIV/AIDS. Increasingly, there are growing numbers of people who are also living with non-communicable disease such as diabetes and heart disease. Although HIV is infectious and diseases like diabetes are not, they share similarities in that they require lifelong management to ensure health. HIV treatment requires a consistent regimen of antiretroviral therapy (ART), while diabetes may require a change in diet as well as regular medication. For policy makers planning health care in South Africa, it is a big challenge to make sure that the state health system has a cost-effective plan to keep these people on treatment and accessing care throughout their lifetime. Although the South African government has made ART available free of charge, recent studies have indicated that many with HIV stop taking the drugs over time. This problem has worsened as the programme has expanded. This is dangerous for their health and is also worrying from a public health standpoint as it could lead to strains of the disease that are resistant to ART as well as increasing the chance of them passing the virus on. Significantly, some clinics dispensing ART have much higher rates of people continuing to pick up their treatment. This study aims to fill knowledge gaps about the factors that influence whether people stay in care, focusing on the ART programme in the Western Cape Province of South Africa. The results of the research will help us work with policy makers in the Department of Health and leaders of community-based organisations to design a larger project that will involve implementing a country-wide programme to achieve more continuous care for people with chronic lifelong conditions. The study will involve researchers from different disciplines who are trained in medicine, the analysis of health systems and policies, social anthropology, public health and pharmacy. We will adopt a method that analyses existing numerical data monitoring how regularly people are collecting the ART drugs at clinics, and other HIV-related data. This will be used to identify which health facilities are performing better than others in terms of keeping people on treatment and engaged in their clinical care. We will focus our work on facilities serving poor populations who are socially marginalised. We will then go on to do more in-depth research in a few facilities which we have assessed as "good performers" and "bad performers" respectively. We will look in more detail at the information about HIV care and also look at indicators of whether people with diabetes are staying in care, using diabetes as an example for non-communicable disease. We will also collect information by observing practices in clinics, and interviewing staff and patients. Interviews will be conducted with decision-makers in the provincial and national Departments of Health. We will investigate the reasons for differences in performance and identify constraints to positive performance. We suspect that the facilities that are managing to keep patients in care, have more innovative organisational practices and have in addition forged partnerships with community-based organisations. This can then help to better support people to take part in managing their chronic illness themselves as well. Such "selfmanagement" is an important factor in poorer settings where the health system cannot provide intensive support from health professionals. We will identify generic factors that are helping to keep people on ART in care and that, if adopted more generally, could contribute to improving care for other chronic conditions also. We will have a workshop with the Department of Health and other stakeholders to discuss how the lessons learned can improve the programmes for chronic disease at national level. This will assist in the design of a bigger intervention and a further research proposal.

Amount: £24,123
Funder: The Wellcome Trust
Recipient: University of Sussex

Moving Bodies: Interactive Spaces. Extension Award. 20 Sep 2011

At-Bristol's experience in exhibition development, learning programmes and online interactivity enables us to produce multi-stranded projects that tackleinterdisciplinary issues and challenges in the 21st century. Moving Bodies will bring together and build on the learning, experience and exhibits developed from previous At-Bristol exhibitions and programmes. Moving Bodies is a 150m2 facilitated, outdoor exhibition that is flexible, energetic and highly interactive. Moving Bodies will tour throughout the UK during 2012. Moving Bodies includes: o Branded inflatable dome - a flexible environment for the exhibition that canbe configuration to suit the venue requirements o Exhibits - 5 portable interactive exhibits, including 10m running track o Satellite link- provides independent link to the web uploading personalised data from the exhibition o Stage area - science theatre demonstration, live lab equipment, Moving Bodies own BIG screen o Branding/marketing tools - entrance mall, barcode collection points, featherflags and graphic barriers. o Generator - giving independence and freedom to travel the exhibition to any venue o Customised Moving Bodies branded transport Through the Moving Bodies exhibition we aim to: o Highlight body energy/power and link to technique as an overarching theme o Create content that explore the human body and its physiology through the exhibits and facilitated demonstrations o Develop a Live Lab experience to further the visitors engagement with the exhibition o Provide personalised experiences that are captured within the exhibition anduploaded to the Explore More website www.movingbodies.org.uk o Highlight the passion, dedication and determination individuals show in their chosen field or profession. Moving Bodies will tour to at least 12 major large scale events throughout the12 regions of the UK. We aim to place the exhibition in the reach of over 1.5 million people and we anticipate 500,000 individuals would receive an engagement experience with the Moving Bodies exhibition. We will operate the tour from May to September 2012. At Bristol has an excellent track record of delivering high quality interactive exhibition that are both permanent and touring. Our project team has a wealth of experience in managing touring exhibitions throughout the UK and overseas including a 6 month travelling exhibition around South Africa, travelling exhibitions to other institutions, exhibit hire and sales around the world. We also have experience of taking interactive exhibitions and showsto large scale events and festivals. Having completed our latest Wellcome funded exhibition All About Us earlier this month, we are ideally placed to build on and continue the challenging work of inspiring our visitors about the beauty and complexity of the human body.

Amount: £150,000
Funder: The Wellcome Trust
Recipient: At Bristol

An integrated study of RNAP transcription. 04 Oct 2011

The archaeal RNAP utilises three general transcription factors TBP, TFB and TFE, whichare homologous to TBP, TFIIB and TFIIE in eukaryotes (6,7). TBP binds to the TATAelement of the promoter and recruits TFB that in turn recruits RNAP and forms thepreinitiation complex (PIC). TFE associates with RNAP and stimulates the separation ofpromoter DNA strands via discrete interactions between its two domains (winged helix[WH] and Zinc-ribbon [ZR]) with the RNAP clamp coiled coil and stalk motifs, respectively(Figure 1B). This results in the loading of the template strand into the RNAP activesite(8). In addition, TFE stabilises the PIC by interacting with the nontemplatestrand(8,9). Spt4/5 is universally conserved in evolution(1,10) and, like TFE, it interactswith the RNAP clamp. Spt4/5 can bind to free RNAPs and efficiently inhibits transcriptioninitiation by closing the DNA binding channel of RNAP(10-12) (Figure 1B). In the PIC hisrepression is overcome by TFE, which displaces Spt4/5 from the RNAP. Followinginitiation, TFE can be retained in the transcription elongation complex (TEC, 9), however,Spt4/5 is able to displace TFE by associating with RNAP, which results in an overallstimulation of transcription processivity(8) (Figure 1A/B). Thus, TFE and Spt4/5 competefor the for the binding to RNAP(8) and the binding and displacement plays a pivotal rolefor the progression through the transcription cycle (Figure 1A).Archaeal transcription systems form an interesting mosaic of an RNAPII-like enzyme thatis regulated by both eukaryote- and bacterial-like transcription factors. In bacteria, NusG(Spt5) has been shown to interact with the elongation factor NusE(4), which is identical tothe ribosomal protein S10. The NusG-NusE interaction could provide the long soughtafter physical link between the transcription and translation machineries (4,5). Archaeaare, like bacteria, prokaryotes and their transcription and translation processes arecoupled(13). Considering the evolutionary conservation of NusG/Spt5 and NusE(S10) itis likely that the interaction between them also connects the two processes in archaea.During termination, the inherently stable transcription elongation complex dissociates,which requires an opening of the RNAP clamp(14),(2). The precise molecularmechanisms are unknown but would seem to require the dissociation of Spt4/5 from theelongation complex, and involve pausing and possibly backtracking - a retrogrademovement of RNAP(5,15). A short poly-U stretch is sufficient to trigger termination ofarchaeal RNAP (16-19). This process readily occurs in vitro without exogenous factorssuch as the bacterial rho helicase, however, the archaeal helicase MJ0669 has beenproposed to function as archaeal termination factor in vivo. Rho is chiefly recruited to theTEC via interactions with the KOW domain of NusG; by analogy it is possible thatMJ0669 is recruited to archaeal TEC via the KOW domain of Spt5. Thus, multipleprocesses converge on RNAP-bound Spt4/5 and thereby regulate transcription.Werner, WT New Investigator Award, body text2The molecular mechanisms outlined above are at best partially understood and severalof the components have not been characterised at all. The function of RNAP subunitsRpo8, Rpo13(20,21) and C34(22) is completely unknown. However, based on theirproximity to the DNA binding channel (Rpo13) and NTP pore (Rpo8) of RNAP we havedeveloped good lead hypotheses regarding their roles during transcription initiation,elongation and termination.The Big Open Questions in the field concern the dynamic aspects of transcription. The12-subunit RNAP (~370 kD) has distinct conformations in the initiation and elongationcomplex, and in the free enzyme – but the transitions between the conformational stateshave never been observed in solution and in real time. Transcription factors are thoughtto aid the changes between the initiation into the elongation complex, and duringtranscription termination – but the mechanisms are not understood. Likewisetranscription factors consist of multiple domains that are rearranged during RNAPbinding. We have developed a fluorescence-based system capable of monitoringconformational changes in RNAP(23) and factors, and have shown that both the RNAPstalk, TFE and Spt4/5 modulate the position of the RNAP clamp in ensemble and singlemolecule FRET experiments (manuscript in preparation). During the transcription cycledistinct protein-protein interactions need to be disrupted (e.g. TFB-RNAP, TFE-RNAP)while others need to be established (e.g. Spt4/5-RNAP) in a sequential manner(8,24,25)– and we have the experimental methods to characterise them. Factors including TBPand TFB are recruited to and dissociate from the gene-specific promoters in a dynamicfashion (2,26). In response to environmental changes (e.g. nutrient shifts) or insults (e.g.UV and heat-shock) the distribution of the transcription apparatus is changingconcomitantly with the gene expression pattern, but it is currently not understood howRNAP and transcription factors (and ribosomes) interact to orchestrate this process. Inorder to elucidate all of the above we want to characterise (i) RNAP/factor mechanismsand interactions in vitro, (ii) the distribution of RNAP/factors on a global level in vivo, and(iii) the whole genome expression profiles in archaea under a range of environmentalconditions.

Amount: £1,419,398
Funder: The Wellcome Trust
Recipient: University College London

Experiencing Koro: On the Margins of Chinese Culture and Western Psychiatry. 17 Sep 2012

This proposal is for conducting preliminary research, writing, and presenting on a project that examines the history of transcultural psychiatry through the lens of the genealogy of a clinical diagnosis known as koro. Koro entered the DSM-IV as a paradigmatic culture-bound syndrome in 1994, and it refers to a persons overpowering belief that his genitalia is retracting and even disappearing. Up to the mid-1960s, doctors believed that this syndrome primarily affected Han Chinese. This view beg an to break down when koro epidemic struck various Southeast Asian countries starting in the late 1960s, involving masses of non-Chinese people, and, eventually, Western African nations by the 1990s. From the start, psychiatrists in Taiwan and Hong Kong have framed koro as a Chinese-style somatization of Western notions of sexual psychogenic illnesses, such as homosexuality, but its international epidemiological inflection continues to offset their ethnically, nationally, and culturally-based e xplanations. Drawing on local archival sources in East Asia, this study aims to chart these interregional historical tensions over time and the increasing pertinence of koro conceptualization to the international professionalization of transcultural psychiatry. The grant will be used for visiting archival holdings in Taiwan and for presenting working papers at various seminars and conferences thereafter.

Amount: £5,000
Funder: The Wellcome Trust
Recipient: University of Warwick

Transforming tissue repair: ‘out-of-the-bag’ elastic meshes that accelerate wound repair 23 Jan 2014

Professor Anthony Weiss, University of Sydney, and collaborator Dr Rob Daniels of Elastagen, are developing a novel product to repair full thickness skin wounds arising from injury, surgery or disease. The product being developed is a mesh produced from elastin, a protein naturally present in the skin as fibres which are responsible for the skin's elastic properties.Elastin also plays an important role in the regeneration of skin tissue following injury; however, as we age our bodies lose the ability to produce sufficient elastin to support this repair process. Through this Wellcome Trust sponsored research and development program the elastin mesh product is being refined to optimise its physical and biological properties and its safety and efficacy will be evaluated in preclinical models.

Amount: £500,000
Funder: The Wellcome Trust
Recipient: Elastagen Pty Ltd

The Dharavi Biennale. 28 Nov 2012

Background: More than half of Mumbai's people live in vibrant localities described by the loaded word slum. A previous Wellcome Trust Award supported Dekha Undekha (Seen and Unseen), a project in which mentor artists and local participants worked together to create a multimedia installation. Held in Dharavi, the city's most well-known informal settlement, Ghari/Ghar pe/At homewas an exhibition about health framed within a virtual home. Big idea: A 33-month programme, the Dharavi Biennale builds on this success. We want to give emerging local artists the opportunity to consolidate their conceptual, practical and leadership skills, bring in new participants, engage more deeplywith health issues, and emphasize sustainability. A series of standalone activities (Artboxes) within the whole will involve about 200 participants. The overarching theme will be recycling: artworks will use recycled materials and will address the health effects of recycled behaviours. Plan: In Year 1, we will build skills and consensus and conduct specific art workshops. In Year2, we will plan and then mount the Dharavi Biennale, an event that brings together multimedia work in an exhibition, performances, screenings and site-specific installations. We estimate a direct audience of 3000. In Year 3, we will emphasize participant autonomy and sustainability. Subgrants over the project cycle will support emerging artists in developing their own activities.

Amount: £137,699
Funder: The Wellcome Trust
Recipient: University College London

The Archaeology of Medicine Roadshow - Extension. 30 Aug 2013

The Archaeology of Medicine Road-show examines the historical impact of biomedical science by providing an interactive educational experience to fifteen schools across Cheshire & Merseyside to inform and educate approximately 1800 Key Stage 3 pupils and 11,000 members of the public about the history & archaeology of Roman and Anglo-Saxon medicine and medical practices in Britain from AD 43-1066. The project aims to foster interdisciplinary collaboration, being developed in partnership with educ ational experts, archaeologists, osteoarchaeologists and Museum practitioners and teachers. It will explore the historical impact of biomedical science, considering ideas and attitudes towards health, medicine and the human body in both Roman and Anglo-Saxon society. The project will create a range on multi-sensory, hands-on activities to allow young people to learn how medicine was practiced in Britain, what cures the practitioners of the day used, what factors affected how long people lived and the state of their health compared to life in the 21st century. This unique approach will reach new audiences not normally engaged with biomedical science. Upon completion of the school visits, the project will tour for five weekends in public sites, including the Museum of Liverpool, Birkenhead Priory & Museum and Epiacum Roman Fort. This unique approach will allow us to reach new audiences not normally engaged with biomedical science whilst testing new methods of engagement, participa tion and education. The Archaeology of Medicine Roadshow will provide a lasting legacy through the creation of a schools loan box and website offering educational resources.

Amount: £18,880
Funder: The Wellcome Trust
Recipient: Big Heritage CIC

Institutional Strategic Support Fund 2011/12. 17 Oct 2011

Neuroscience & Behaviour Leicester has clear strengths in neuroscience and behaviour research and our previous ISSF encouraged new appointments and substantial grant funding Genomes and ‘Big Data’ Genome variation and dynamics is a long-standing cornerstone of research excellence at Leicester. Stratified Medicine. Modern genomic and biomarker studies are revealing heterogeneity in susceptibility, prognosis and treatment responses of patients assigned to established diagnostic groups. Our previous ISSF award allowed us to invest in next generation sequencing and proteomic infrastructure to interrogate this heterogeneity Public Health Our Population Science and Diabetes research themes are central to Leicester’s contribution in bridging the second translational gap, converting preclinical and clinical research into public health outcomes. (ii) Facilitation of collaborative initiativesLeicester’s biomedical research strategy is driven through our College research themes. However, all themes have affiliates from other Colleges, with a specific Life-Sciences Interface Theme crossing our College and the College of Sciences and Engineering (iv) Public engagement strategyOur new ISSF award will allow us to develop and deliver a more focused public engagement (PE) strategy that will build upon the previous general good practice within our College. We will develop a coordinated plan via two complementary mechanisms

Amount: £500,000
Funder: The Wellcome Trust
Recipient: University of Leicester

BEYOND Cancer: Using Big Data to Identify Opportunities for Cardiovascular Disease Prevention after Cancer. 27 May 2015

The long-term health of the growing numbers of cancer survivors is an increasing priority. Certain cancer treatments have known or suspected cardiotoxicities, but the overall risks of specific cardiovascular diseases among survivors of different cancers have not been systematically quantified. It is also unclear whether those at highest risk are being adequately identified by existing risk stratification tools, and offered appropriate preventive interventions. Harnessing linked e-Health data from the UK/Denmark to generate large site-specific cancer survivor cohorts, I will address these issues using predictive and causal modelling, matched cohort designs, and descriptive epidemiology. The goals are to: 1) QUANTIFY the relative and absolute risks of key cardiovascular diseases in survivors of specific cancers, and investigate determinants of increased risk; 2) IDENTIFY those at risk both with existing risk stratification tools, and by developing recalibrated and new tools inco rporating cancer-specific information, comparing the predictive accuracy of these approaches; 3) INFORM PREVENTION by investigating whether recommended pharmacological interventions to prevent cardiovascular disease are optimally implemented among cancer survivors. The work will also lay foundations for better e-Health research in this field, by building experience, developing methods, and establishing access/linkage to rich new sources of cancer treatment data.

Proliferation and death of T-cell subsets following vaccination. 12 Jul 2006

The kinetics of T-cell proliferation and death following vaccination in humansare poorly understood. There is an immense effort underway to develop a new generation of vaccines to generate protective T-cell responses against a number of key pathogens responsible for morbidity and mortality on a massive scale. A greater understanding of the processes that lead to effective and durable memory could have a major impact on the design of new vaccines and theimmunization regimes, perhaps allowing development of new adjuvants that enhance survival of memory T-cells following the initial 'burst' response.Labelling dividing cells with deuterium presents a new, safe, radiation-free method of measuring kinetics of antigen-specific T-cells and their subsets. I propose to use this technique to measure T cell responses induced by the tuberculosis vaccine MVA85A in eight healthy BCG-primed volunteers.I will also study apoptosis of vaccine-induced T cells following vaccination with new malaria and tuberculosis vaccines using an apoptosis assay and caspase activation assay. This research will utilise samples from twelve volunteers in upcoming studies in the Oxford clinical trials programme.I also plan to use anti-apoptotic agents in vitro to try modifying this process to increase the size of the resulting memory pool.

Amount: £242,111
Funder: The Wellcome Trust
Recipient: University of Oxford

From Generation to Reproduction. 14 May 2009

To reassess change and continuity in practices and meanings of 'generation' and 'reproduction', we will combine expertise in periods from antiquity to the present, and approaches from historical demography to history of science. Four teams will work in complementary research strands: 1. 'Patients and practitioners' will study the 'reproductive patient' to recover the wider patterns of intervention and concern. 2. 'Reproducing generations: conception and survival' will consider how matern al, fetal, infant and childhood health affected adult health and fertility, and the reproductive impact of sexual behaviour and venereal disease. 3. 'Representation and communication' will show how changing understandings of sex, development and evolution were produced, debated and used. 4. 'C20 transformations: technologies, experiences and regulation' will make a concerted attempt to account for the recent reproductive revolutions. Using research leave, research assistance and events, we w ill tackle the big questions, and produce high-quality publications (essay collections and single-authored books:Q14) and funding applications. An accessible, co-edited volume will provide a fresh vision for the whole field. We will continue to innovate in teaching and training, and expand a critical mass of expertise. We also propose enhanced public engagement, including 'The book of generation', a major exhibition at Cambridge University Library, and regular outreach activities (Q16).

Amount: £785,058
Funder: The Wellcome Trust
Recipient: University of Cambridge

Global Tuberculosis Control, 1920-1970: The Mass BCG Campaign and Antibiotics on Indian Reservations and in the Developing World. 31 Aug 2007

I will conduct research in the UK National Archives on the Colonial and Foreign Offices' involvement in the origins and development of TB control in, primarily, Africa; if time allows I will begin to explore archival material related to India and New Zealand. I will be looking at records concerning two research questions: how in the 1950s did the Colonial and Foreign Offices discover TB as a problem in Africa? Second, how, principally via the Medical Research Council, did work proceed to control the disease? Looking at these questions fits into a larger research agenda of mine that is principally concerned with the mass TB BCG vaccine campaign lead by the WHO and UNICEF after World War II and the development of several antibiotics from the late 1940s through the mid-1960s. The larger project will result in a book on the origins and development of the global control of TB.

Amount: £810
Funder: The Wellcome Trust
Recipient: University of Virginia

Playing God 18 Apr 2007

Playing God Playing God (working title) is a theatre piece created, performed and aimed at primarily Deaf People looking at issues surrounding Cochlear Implants. This play is about two couples, one hearing working within audiology, one Deaf with a Deaf baby. The lives and attitudes of the couples become intertwined over the question of what provisions are  to be made for the Deaf baby: cochlear implants and oral education or British Sign Language (BSL). For the Deaf couple the issue puts their relationship at  pinnacle, the father being in favor of BSL whilst the mother becomes  doubtful. The play has been carefully researched and leaves the audience to make up its own mind where they stand on the issue. The play will be performed in central theatres around the UK where there is a large Deaf community - Chelmsford, Brighton, Exeter, Bristol, Birmingham, Derby, Wolverhampton, Manchester, Liverpool and Leeds. We will also take part in the Disability Arts Festival in Edinburgh. There will be 10 nights at Soho Theatre in London which is already funded. The aims are to raise awareness, present facts, and encourage debate about Cochlear Implants. The primary audience will be Deaf people, but will also be of interest to Hard of Hearing and/or Hearing people who may have a Deaf child, family or friends. The issue of Cochlear Implants is very much a 'hot topic' amongst the Deaf community and there is a big lack of awareness of the medical facts and implications. This will be addressed using theatre methods directly accessiblt to Deaf audiences.

Amount: £30,000
Funder: The Wellcome Trust
Recipient: Deafinitely Theatre

Playing God 29 Nov 2007

Playing God Playing God (working title) is a theatre piece created, performed and aimed at primarily Deaf People looking at issues surrounding Cochlear Implants. This play is about two couples, one hearing working within audiology, one Deaf with a Deaf baby. The lives and attitudes of the couples become intertwined over the question of what provisions are  to be made for the Deaf baby: cochlear implants and oral education or British Sign Language (BSL). For the Deaf couple the issue puts their relationship at  pinnacle, the father being in favor of BSL whilst the mother becomes  doubtful. The play has been carefully researched and leaves the audience to make up its own mind where they stand on the issue. The play will be performed in central theatres around the UK where there is a large Deaf community - Chelmsford, Brighton, Exeter, Bristol, Birmingham, Derby, Wolverhampton, Manchester, Liverpool and Leeds. We will also take part in the Disability Arts Festival in Edinburgh. There will be 10 nights at Soho Theatre in London which is already funded. The aims are to raise awareness, present facts, and encourage debate about Cochlear Implants. The primary audience will be Deaf people, but will also be of interest to Hard of Hearing and/or Hearing people who may have a Deaf child, family or friends. The issue of Cochlear Implants is very much a 'hot topic' amongst the Deaf community and there is a big lack of awareness of the medical facts and implications. This will be addressed using theatre methods directly accessiblt to Deaf audiences.

Amount: £6,227
Funder: The Wellcome Trust
Recipient: Deafinitely Theatre