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Recipients:
University College London
University of Cambridge
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Results

Identification and functional analysis of susceptibility genes in multifactoral disease: Award for Years 4 and 5. 20 Sep 2006

The Wellcome Trust Centre for Human Genetics was established in 1994 to undertake research into the genetic basis of common diseases. The scientific objective of the Centre is to gain insight into mechanisms controlling geneticsusceptibility to human disease including the localization and identification of disease genes, functional characterization of gene variants responsible forsusceptibility, understanding how gene variants contribute to risk of disease in the population and how genetic factors contribute biologically to a diseaseprocess. In order to achieve this scientific objective the Centre's strategy was to bring together multidisciplinary research groups collaborating on humanand rodent genetics, genetic epidemiology, functional analysis of disease genes, cell and developmental biology and structural biology. In addition, theCentre has a strong focus of expertise, equipment and resources centralized inCore groups allowing all research groups to benefit and expand their research strategies. The Core groups in Genomics, Molecular Cytogenetics and Microscopy, Bioinformatics and Statistical Genetics, and Transgenics provide first-rate services and perform research and development on new platform technologies as well as algorithms and databases needed to analyse complex datasets. This application is to continue our Centre status and provide funding for the running of these Core groups over the next five years.

Amount: £4,184,432
Funder: The Wellcome Trust
Recipient: University of Oxford

Core support for Wellcome Trust/Cancer Research UK Gurdon Instiute. Award for years 4 and 5. 20 Sep 2006

This application requests the continuation of core support to the Wellcome Trust/Cancer Research UK Gurdon Institute. The aim of the Institute, an integrated part of Cambridge University, is to contribute to an understanding of normal animal development, including the processes of cell differentiation, morphogenesis and cell proliferation, and to explain how, should these processes fail, cancers may arise. The Institute attempts to achieve these objectives by recruiting the best scientists and by ensuring that they have the best possible environment for their work. Recruitment is carried out by a committee of Group Leaders, with the main criterion for appointment being scientific excellence. This application is concerned with providing the best scientific environment for our researchers, and indeed the Institute's core support is one of its most important assets, allowing our scientists to spend as much time as possible on their work. This support provides practical assistance, such as media preparation, and secretarial and administrative assistance, including help with grant applications and equipment procurement. It also provides computer staff and a bioinformatician, as well as expertise in confocal microscopy. Core support is essential if the Institute is to maintain its position as a leading centre of cell, molecular and developmental biology.

Amount: £3,005,149
Funder: The Wellcome Trust
Recipient: University of Cambridge

WELLCOME TRUST CENTRE FOR STEM CELL RESEARCH 20 Sep 2006

The new Institute for Stem Cell Biology in Cambridge will be an international centre of excellence in fundamental stem cell research. The Institute will focus on definition of the genetic and biochemical mechanisms that control stem cell fate, providing foundations for applications in disease modelling, drug discovery and regenerative medicine. This proposal is for provision of core resources for embryonic stem cell manipulation and transgenesis. A central resource of skilled personnel will maximise research productivity and continuity, promote cooperation and synergy, and accelerate technological innovation. Timely and efficient production of customised gene-modified stem cells and mice is essential underpinning. Specialised expertise will support advanced genetic engineering of mouse and human stem cells, and operation of robotic platforms to develop screening methodologies for isolating genetic, protein and chemical regulators. A dedicated PdD programme in stem cell biology will capitalise on the opportunity for high level research training provided by the intellectual environment and core facilities in the Institute. A Strategic Award will immediately establish the Institute for Stem Cell Biology amongst the best-resourced and most attractive environments for stem cell research world-wide, providing a magnet for recruitment, and a much-needed focus for UK and European stem cell biology.

Amount: £6,956,531
Funder: The Wellcome Trust
Recipient: University of Cambridge

VALUE IN PEOPLE AWARD. 30 Aug 2006

Not available

Amount: £300,000
Funder: The Wellcome Trust
Recipient: University College London

Nuclear magnetic resonance spectroscopy as a tool to study the structure, function, dynamics and folding of proteins: University Award for a research technologist in biomolecular NMR. 21 Feb 2006

The key goal of this proposal is to identify ways in which state-of-the-art NMTo characterise the structure, dynamics and Ca2+-binding properties of cbEGF dTo understand the importance of the covalently bound heme in c-type cytochromeTo characterise the structure, dynamics and interactions of the redox protein To characterise the structure, dynamics and ligand-binding properties of proka

Amount: £303,200
Funder: The Wellcome Trust
Recipient: University of Oxford

Fragment-based approaches to the design of candidate drugs that interrupt protein-protein interactions involved in cell regulation. 28 Apr 2006

Structure base drug design and Structural bioinformatics are emerging areas that could help lead drug discovery. The Trust has recently awarded £1,022,854 to Professo'r Sir Tom Blundell and colleagues at University of Cambridge to identify candidate ligands that may advance cancer therapeutics. The applicants plan to extend fragment-based approaches and design novel candidates that interrupt protein-protein interactions exploiting small pockets in protein-protein interfaces, particularly where one component is :a flexible polypeptide that assembles to give a specific structure only in the multiproteiri complex. They are specifically examining the multiprotein complex of human recombinase, Rad51, and the product of the breast cancer associated gene, BRCA2. The applicants plan to screen using X-ray, NMR, mass spectrometry, and other biophysical approaches, together with biochemical and biological assays to select and validate useful ligands. This project could identify drugs that block the BRCA2-RAD51 interaction to sensitise canc~r cells to radiation, DNA cross-linking agents or replication inhibitors, or to directly induce cancer cell death during proliferation. In addition, this project has the potential to validate that protein protein interactions are potentially druggable

Amount: £1,022,854
Funder: The Wellcome Trust
Recipient: University of Cambridge

Phase II studies with MVA85A in Cape Town 12 Jun 2006

Summary not available

Amount: £75,000
Funder: The Wellcome Trust
Recipient: University of Oxford
Amount: £213,508
Funder: The Wellcome Trust
Recipient: University of Cambridge

SONHIA - study of newly diagnosed HIV infection amongst Africans in London. 23 Jan 2006

HIV/AIDS amongst Britain's African communities is a major public health concern, yet to date, relatively little research has focused on this group. This study will increase our understanding of the factors which influence access to, and utilisation of, HIV treatment and prevention services among African communities in Britain. It will also help to inform the development of culturally appropriate HIV health promotion interventions aimed at increasing service uptake within these communities. Plan of investigation: The study population will be all African patients attending in- or outpatient services at selected London HIV treatment centres. To date 7 centres have agreed to participate. The project will consist of two inter-linked components implemented over 2 years: i) A qualitative study amongst a purposively selected sample of newly diagnosed HIV positive Africans employing in-depth interview techniques, and ii) A cross-sectional survey of newly diagnosed HIV positive Africans presenting to specialist HIV services in London. Key workers at each study site will recruit patients and distribute the questionnaires. Dr Burns will perform the interviews. 'Framework' will be used for organising and analysing the qualitative research. Quantitative data analysis will be using STATA 6.0. The questionnaire, topic guide and protocol will be submitted to all appropriate Research Ethics Committees for approval. All patients will be given written information regarding the study and written informed consent will be obtained prior to participation. An African Community Reference Group will be set up to oversee all stages of the study design. Background preparation for the study will be undertaken as part of the MSc dissertation. Study outputs: Peer reviewed publication on health care seeking behaviours among Africans and reasons for delayed presentation; contextual information on healthcare access and utilisation, stigma, onward HIV transmission risk and proportion of HIV infections acquired within the UK.

Amount: £23,380
Funder: The Wellcome Trust
Recipient: University College London

Antigen presentation and dendritic cell function in malnourished children. 15 Feb 2006

Malnutrition has a major impact on the health of children and is responsible for approximately 50% of all childhood deaths, mostly from infectious disease. The precise relationship between malnutrition, immune competence and infectious disease is poorly understood, yet these interrelated factors are the critical determinants of childhood morbidity and mortality. Though neglected in recent years, the association of malnutrition with defects in cell mediated immunity (CMI) is well established. Studies of CMI in malnutrition have focused on T cells, however, central to the successful generation of T cell responses is the ability of the host to present antigen to T cells. The professional antigen presenting cell in humans is the dendritic cell (DC), yet DCs have not been studied in any great detail in malnutrition, partly because the technology for their isolation and culture have only recently been established. Abnormalities of DCs have been described in early life and in association with infections such as HIV and malaria. T cell abnormalities described in severe malnutrition may be secondary to abnormalities of DCs. We propose to study DC function in a group of severely malnourished children on admission to a nutrition ward and then follow their DC function through recovery. The chosen study site in Zambia provides the ideal environment for such a study as the nutrition ward at Lusaka University Teaching Hospital admits 1,800 severely malnourished children a year and has an active research unit. During the study we will (1) characterise the patterns of DC phenotype and function in severe malnutrition, (2) describe the effects of severe malnutrition, HIV and measles on DC function, and (3) describe the impact on DC function of in vitro supplementation with micronutrients, thought to contribute to DC function. This study will provide insights into the mechanism of immune deficiency in malnutrition while also providing a rational basis for the development of novel focused micronutrient supplementation aimed at improving immune function in the severely malnourished child.

Amount: £23,105
Funder: The Wellcome Trust
Recipient: University College London

Collaborations between developing and developed countries in advancing biomedical population genetics, neglected diseases and bioprospecting R&D: developing policy and practice guidelines for going forward in 21st century. 22 May 2006

Studentship in Biomedical Ethics Project title: Collaborations between developing and developed countries in advancing biomedical population genetics, neglected diseases and bioprospecting R&D: Developing Policy and Practice Guidelines for Going Forward in the 21st century. The project will examine the structure, organisation and interplay of key ethical, socio-economic, health-policy and commercial concerns regarding the establishment of sustainable support systems (policies, institutions, R&D and commercial practices) for biomedical collaborations between developing and developed countries, framed around a need to align participant incentives- within a system that promotes and ensures ethical practice. It will elucidate the benefits and shortcomings of current practice; investigate the interplay between trade-offs and competing tensions facing collaborative efforts (e.g. exploration versus exploitation, short vs long-termism, trust vs vigilance, competition vs cooperation, opportunism vs altruism, planning vs emergence); highlight implications; and draw novel collaboration performance measures and improved guidelines for addressing a series of collaboration -specific issues in a multidisciplinary and integrated manner. These include access to genetic resources, benefit sharing and ethical concerns, IPR protection, technology transfer and capacity building in developing countries. Research will build on theoretical and empirical evidence from the fields of global health, bioethics, alliance theory, innovation management and development studies. The project will employ a multiple methodology approach, combining evidence from comparative case studies of collaborative R&D efforts at biomedical centres in the developing world (e.g. at sponsor institutions: Africa Centre for Health and Population Studies and Wellcome Trust's South East Asia Overseas Unit), interview data, company profiles, descriptive statistics, bibliometric and patent data. Empirical evidence for best-practice transfer will draw on contextual insight from the fields of population genetics, neglected diseases and bioprospecting. Such theoretical and practical advancements are pivotal towards spring-boarding cross-national collaboration practice in the biomedical sector, and ensuring that both "First" and "Third World" parties offer each other better credibility, stronger contributions and more equitable benefit distributions in turn.

Amount: £8,976
Funder: The Wellcome Trust
Recipient: University of Cambridge

Slippery slopes in the history of in vitro fertilisation and therapeutic cloning: the influence of ethical argument on the development of law and policy. 26 Apr 2006

IVF and embryo research have been the subject of controversy for more than thirty years and have been attacked on the basis that allowing them is the beginning of a 'slippery slope' towards eugenics, state control of reproduction and reproductive cloning. Debates about these technologies have been characterised by fears of the 'uncontrollability' of science and the consequences of uncontrolled scientific development Robin Henig argues in her history of the reproductive revolution that many of the slipper slope ethical arguments initially raised against IVF are now being used against human cloning and genetic engineering. However, she points out that many of the predictions made in arguments have not occurred. This project will test this conclusion by examining the influence of slippery slope ethical arguments on the historical development of legislation regulating IVF - a technology that is now widely accepted - and therapeutic cloning technologies. The project will: Produce empirical findings on the influence of slippery slope arguments on policy development; Examine how slippery slope concerns in public and academic ethical discourses affect policy development; Compare the outcomes predicted in these arguments, with the actual outcomes of the development of these technologies to examine the concept of fallacy within slippery slope arguments; and Consider the ethical validity of resulting legislative measures given the actual outcomes.

Amount: £3,700
Funder: The Wellcome Trust
Recipient: University of Oxford

The Reality of Nervous Disorders in Britain, 1760-1820. 23 Jan 2006

The Reality of Nervous Disorders in Britain, 1760-1820 The purpose of my D.Phil, is to bring some much needed reality of the phenomenon of fashionable disorders. Instead of the usual theoretical, philosophical, and fictional discourse employed by previous historians, I have begun a detailed examination of newspapers, hospital registers, journals of sufferers, and the writings and case notes of various town doctors to determine the types of treatments given to nervous patients, their perceived chance of recovery from these disorders, as well as their number, class and location. My research also aims to explore the lives of the "nerve doctors", and to discover the motivations which drove so many of them to publish on the subject. It is only through this kind of a systematic review that the presence of fashionable disorders in the eighteenth century can effectively shed light on the boundaries of politeness and the extent to which fashion played a role in constructing the 'Age of Sensibility'. The plan for my research is threefold: I need to continue my study of the popular discourse surrounding nervous disorders, and to examine the lives and surviving records of the doctors treating nervous disorders, as well as the lives and experiences of their nervous patients. To date I have focused my attention on the sources available in Oxford's Bodleian library. The Bodleian's manuscript collections have also proved very helpful, providing me with unpublished letters and lecture notes by doctors like Thomas Beddoes and William Cullen. Aside from London, my research will necessarily take me to Scotland, as it was primarily the Scottish nerve doctors like William Cullen and John Gregory that taught British physicians from the 1750s to the end of the century. There is little question that the sources exist which will answer my questions regarding the reality of nervous disorders in the eighteenth century and will heighten our appreciation of the importance of this subject.

Amount: £1,500
Funder: The Wellcome Trust
Recipient: University of Oxford