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The National Lottery Community Fund (226,066) The Wellcome Trust (16,854) Co-operative Group (16,503) Sport England (15,905) The National Lottery Heritage Fund (10,201) Garfield Weston Foundation (6,126) Lloyds Bank Foundation for England and Wales (5,467) The Henry Smith Charity (4,590) Northern Rock Foundation (4,331) Community Foundation serving Tyne & Wear and Northumberland (4,320) Esmée Fairbairn Foundation (4,221) BBC Children in Need (4,183) Woodward Charitable Trust (2,767) Quartet Community Foundation (2,683) Department for Transport (2,577) The Tudor Trust (2,554) City Bridge Trust (2,480) Paul Hamlyn Foundation (2,367) Wolfson Foundation (2,210) Community Foundation for Surrey (1,987) Essex Community Foundation (1,891) Greater London Authority (1,846) Heart Of England Community Foundation (1,727) County Durham Community Foundation (1,659) London Borough of Southwark (1,648) The Robertson Trust (1,542) Comic Relief (1,442) Suffolk Community Foundation (1,428) Glasgow City Council (1,365) The Clothworkers Foundation (1,358) Somerset Community Foundation (1,259) Nesta (1,247) Guy's and St Thomas' Charity (1,230) Corra Foundation (1,184) London Catalyst (1,174) Oxfordshire Community Foundation (1,139) Birmingham City Council (1,103) CAF (1,004) Leeds Community Foundation (905) Masonic Charitable Foundation (895) Sussex Community Foundation (878) Power to Change Trust (870) Two Ridings Community Foundation (792) Trafford Housing Trust Social Investment (779) Ministry of Justice (774) National Churches Trust (760) Walcot Foundation (755) Devon Community Foundation (715) The Dulverton Trust (680) A B Charitable Trust (665) See Less

Results

Amount: £43,104
Funder: The Wellcome Trust
Recipient: University of Oxford

MSc in the History of Medicine. 30 Aug 2006

Not available

Amount: £19,458
Funder: The Wellcome Trust
Recipient: University of Manchester

Intestinal homeostasis: identification of the factors that influence the balance between regulatory and effector cells in the intestine and how alterations in these can lead to chronic intestinal inflammation. 24 Apr 2006

Using mouse models we have shown that colitis can develop as a consequence of excessive innate or T cell dependent responses and that these can be controlled by immune suppressive regulatory T cells (TR). Our recent studies suggest compartmentalization of the pathological response with IL-23 driving local intestinal inflammation and IL-12 mediating the systemic response. We will further characterize the cellular and molecular pathways of IL-23 driven intestinal inflammation, including IL-17 production, to identify their role in innate and T cell dependent colitis. Foxp3 and IL-10 indicator mice will be used to analyse the distribution of bacteria-induced and naturally arising TR cells in vivo as they respond to inflammation and determine their functional properties in distinct anatomical compartments. CD103+ mucosal DC's plays a key role in TR function and will determine how this DC subset influences the balance between effector and TR responses. We have also newly identified the G-protein coupled receptor Gpr 83 as a potential marker for TR cells and using Gpr83-/- mice we will assess its functional role. The results of these studies will facilitate the development of novel therapeutics for chronic inflammatory diseases via the manipulation of TR cells and tissue specific inflammatory pathways.

Amount: £2,082,531
Funder: The Wellcome Trust
Recipient: University of Oxford

Determination of the role of site specific GPCR phosphorylation in cellular responses. 29 Jun 2006

Studies on the Mechanisms and Functional Consequences of Phospholipase C-Coupled Receptor Phosphorylation Many neurotransmitter, neuromodulator, hormone and growth factor receptors are coupled, via G-proteins, to the activation of phospholipase C (PLC). The processes that regulate this signal transduction pathway are, therefore, central in the cellular responses mediated by a diverse group of biological ligands, in addition to being important for the action of many therapeutic drugs. This project proposes to investigate the involvement of receptor phosphorylation in the regulation of PLC-coupled receptors. The investigation is aimed at three levels; (i) identification of the kinases responsible for PLC-coupled receptor phosphorylation, (ii) the functional consequences of receptor phosphorylation and (iii) the relevance of phosphorylation to signalling in an intact tissue; airway smooth muscle. I have recently been successful in the purification of a novel receptor-specific kinase (MRK) that is able to phosphorylate the PLC-coupled m3-muscarinic receptor. One of the major aims of this project is to obtain a cDNA clone for MRK. Analysis of the modes of MRK regulation will also be conducted, in addition, to investigation of the receptor-substrate specificity of MRK. Functional studies on the role receptor phosphorylation plays in the regulation of receptor/PLC coupling will form an important part of the project. This will benefit from the excellent infra-structure already in place in the department, that allows for a mix of molecular approaches and detailed analysis of receptor-signalling properties. It is planned to identify the sites of phosphorylation on the PLC-coupled m1- and m3-muscarinic receptors and delete these sites by point mutagenesis. Detailed functional analysis of mutant and wild type receptors will then be pursued. This will be coupled with reconstitution studies, and transfection studies where muscarinic receptor subtypes will be co-expressed with receptor-specific kinases and dominant negative kinase mutants. Particular emphasis will be placed on the possible role phosphorylation plays in receptor desensitisation, and receptor/G-protein coupling.

Amount: £1,328,110
Funder: The Wellcome Trust
Recipient: University of Leicester

Funds for administrative support. 26 Apr 2006

Wellcome Trust Cardiovascular Research Initiative. The University of Edinburgh has had considerable recent success in setting up new interdisciplinary centres for biomedical research and the intention of the University to institute a Centre for Research in Cardiovascular Biology (CRCB) was highlighted in the submission for the 1996 RAE well in advance of publicity for the CVRI. The CRCB will be a network of interacting groups within an interdisciplinary 'centre without walls'. A Scientific Advisory Board (SAB) will provide the necessary management structure and administrative support for the Initiative to ensure quality in both research and training. As indicated in our original submission, the SAB will comprise Profs Fox, Haslett, Seckl, Webb and Wyllie, as well as all senior and principal fellows related to the Initiative. Therefore, it is envisaged that Dr Mullins would be a member of the SAB from the outset and that Dr Brown would join in due course. The leader of the Initiative will be Prof Webb, a clinical pharmacologist and clinician in cardiovascular medicine who has a background in cardiovascular science, a major research interest in endothelial function, and whose work bridges clinical and laboratory based-research. This group has the following major responsibilities: In research: To review overall strategy and focus, and set the priorities for research; to review ongoing research programmes and assess new proposals for funding; to assess proposals for senior or principal fellows; and to consider applications from potential visiting research staff. In training: To review ongoing training fellowships; to approve and prioritise new training opportunities and requirements; to consider applications for research leave in the UK or abroad to learn new techniques; to implement a programme of research seminars; and to liaise with the University Faculty of Medicine and, where relevant, with the Postgraduate Dean to address and facilitate clinical training needs, a role which the four clinical professors of medicine who are members of the SAB are particularly well placed to accomplish.

Amount: £45,000
Funder: The Wellcome Trust
Recipient: University of Edinburgh

Balance of funds awarded to Edinburgh CVRI. 26 Apr 2006

Wellcome Trust Cardiovascular Research Initiative. The University of Edinburgh has had considerable recent success in setting up new interdisciplinary centres for biomedical research and the intention of the University to institute a Centre for Research in Cardiovascular Biology (CRCB) was highlighted in the submission for the 1996 RAE well in advance of publicity for the CVRI. The CRCB will be a network of interacting groups within an interdisciplinary 'centre without walls'. A Scientific Advisory Board (SAB) will provide the necessary management structure and administrative support for the Initiative to ensure quality in both research and training. As indicated in our original submission, the SAB will comprise Profs Fox, Haslett, Seckl, Webb and Wyllie, as well as all senior and principal fellows related to the Initiative. Therefore, it is envisaged that Dr Mullins would be a member of the SAB from the outset and that Dr Brown would join in due course. The leader of the Initiative will be Prof Webb, a clinical pharmacologist and clinician in cardiovascular medicine who has a background in cardiovascular science, a major research interest in endothelial function, and whose work bridges clinical and laboratory based-research. This group has the following major responsibilities: In research: To review overall strategy and focus, and set the priorities for research; to review ongoing research programmes and assess new proposals for funding; to assess proposals for senior or principal fellows; and to consider applications from potential visiting research staff. In training: To review ongoing training fellowships; to approve and prioritise new training opportunities and requirements; to consider applications for research leave in the UK or abroad to learn new techniques; to implement a programme of research seminars; and to liaise with the University Faculty of Medicine and, where relevant, with the Postgraduate Dean to address and facilitate clinical training needs, a role which the four clinical professors of medicine who are members of the SAB are particularly well placed to accomplish.

Amount: £14,243
Funder: The Wellcome Trust
Recipient: University of Edinburgh

Antigenic variation and transmission of African trypanosomes. 23 Jan 2006

African trypanosomes evade host specific immunity by undergoing antigenic variation, the differential expression of a family of ~1000 Variant Surface Glycoprotein (VSG) genes. Several VSG gene switching mechanisms operate in laboratory-adapted trypanosomes, which have a greatly reduced VSG switch rate, but in high-switching, non-adapted lines, we have now found there is one dominant mechanism, gene duplication, that preferentially uses telomeric genes. VSGs are first expressed in the metacyclic stage in the tsetse fly, where genes are activated by a mechanism of random selection of telomerically located promoters. Together, these findings lead to the proposal that VSG gene activation systems involve telomere silencing, which can be alleviated for individual switch events by specific, positive factors. I propose to dissect the gene duplication mechanism and its possible hierarchical nature in bloodstream trypanosomes, and the promoter activation mechanism in the tsetse fly phase. Simultaneously, basic characterization of telomere silencing has begun with a specialist laboratory, and the aim is to draw together all these strands. VSG expression is closely linked with other essential phenotypes, and I aim also to assess the nature and extent of diversity in these phenotypes in the critical metacyclic population. We specialize in study of trypanosomes in an organismal background, and the proposed studies would lead to an integrated understanding of how trypanosomes survive through programmed diversification.

Amount: £759,516
Funder: The Wellcome Trust
Recipient: University of Glasgow

A contribution to the refurbishment of laboratory space at the Sir William Dunn School of Pathology for Prof Robertson to facilitate her move from the WT Centre for Human Genetics. 20 Sep 2006

We are studying the complex cellular interactions underlying early mammalian development, and in particular the signals provided by members of the TGFß superfamily of secreted growth factors. We have previously shown that nodal activity is required for primitive streak formation and anterior patterning during gastrulation, and at later stages for establishment of the L/R body axis. We also described an essential function contributed by the Smad2 protein, the intracellular effector downstream of TGFß/activin receptors. The proposed experiments studies further dissect nodal contribution(s) during morphogenesis of the mouse organiser and establishment of the L/R body axis. We will use gene targeting techniques to selectively delete enhancer sequences controlling asymmetric and node specific nodal expression domains respectively. Using a novel in vivo cell marking system we plan to describe mesodermal subpopulations derived from the node and its progenitors. We will also test the role of the Smad2 pathway during node morphogenesis. Overall the proposed experiments should provide a clearer understanding of TGFß signalling pathways during mouse development.

Amount: £200,000
Funder: The Wellcome Trust
Recipient: University of Oxford

An analysis of natural immunity to invasive pneumococcal disease among infants and young children in Kilifi, Kenya. 27 Oct 2005

Invasive pneumococcal disease (IPD) causes approximately 1 million deaths in infants and young children in the developing world each year. Although protein conjugated pneumococcal vaccines are highly efficacious against IPD they are unlikely to be made widely available in Africa for reasons of cost. Vaccination exploits natural mechanisms of immunity in humans and yet the basis of immunity to pneumococcal disease among infants is not known. African infants have low or undetectable concentrations of serotype-specific antibody, the major defence mechanism of adults, but most infants still do not develop disease despite frequent exposure to the pathogen. The rise in anti-capsular antibody concentrations towards adults levels takes place months or years after the sharp decline in the risk of IPD during the second year of life suggesting that protection at this point is independent of anti-capsular responses. Alternative explanations of immunity in infants are the functional quality, rather than quantity, of anti-capsular antibody, the kinetics of the anti-capsular response, or mucosal responses to capsular antigens which mature more rapidly then systemic responses. Alternatively, immunity may be determined by antibodies to non-capsular targets such as C-polysaccharide or common pneumococcal proteins, pneumolysin, PspA and PsaA. Some susceptibility to disease is clearly attributable to genetic variables such as sickle cell disease, deficiency of mannose binding protein and variations in the receptor for IgG2, Fc gamma RIIa. So far it has not been possible to examine the correlation between serological factors and protection from IPD in humans because of the difficulty of obtaining serum samples before the onset of disease. The original feature of this study is that it overcomes this limitation by nesting a case-control study of immunological variables within a cohort of 5,000 infants who are followed up with 3 monthly serum and saliva samples throughout the first 21 months of life. The study will be conducted in a population with a high incidence of IPD, which will be detected by a combination of sensitive and specific diagnostic techniques to yield approximately 100 cases. Studies of additional value will be incorporated into the design to examine epidemiological risk factors for IPD, and to describe the morbidity experience of the cohort. Finally, the design offers considerable scope for immunological case-control studies of other major infectious diseases of children.

Amount: £574,389
Funder: The Wellcome Trust
Recipient: University of Oxford

The cellular mechanisms of cortical map reorganisation in primary sensory cortex. 12 Jul 2006

A large part of the neocortex is given over to topographic representations of sensory inputs and motor outputs. Many of these maps express experience-dependent plasticity in adulthood. This is of great neurological interest because cortical reorganisation probably contributes to recovery from brain damage. Harnessing experience-dependent plasticity potentially offers therapeutic benefits. However, the simple strategy of maximising plasticity will not work because excess or aberrant reorganisation may cause disease. Realising any therapeutic gain will, therefore, require an understanding of the cellular mechanisms that drive cortical map reorganisation. The sensory input from rat whiskers to primary somatosensory cortex provides an ideal model system to study cortical map plasticity because brief periods of whisker trimming results in reorganisation of the corresponding cortical map. I will investigate the underlying cellular mechanisms level by preparing in vitro brain slices of primary somatosensory cortex that cut across the whisker barrel rows. My general strategy will be to patch clamp paired neurons in the supragranular cortex and to characterise the electrophysiology and the neuroanatomy of the connection between the neurons. Short-term synaptic dynamics will be used as a probe to assess the strength of single-axon connections. The neurons will be filled with biocytin. Triple-label immunofluorescence combined with confocal microscopy will detect biocytin filled neurons, presynaptic boutons and postsynaptic density. Colocalisation of the three labels indicates the site of synapses between the two neurons under study. I will define how the short-term dynamics of excitatory intracortical synapses vary with the period of deprivation and assess whether synaptic number changes contemporaneously. A parallel study will focus on the synaptic dynamics of inhibitory circuitry in supragranular cortex. This will determine whether inhibition is affected by sensory deprivation and help to assess if the balance of excitation and inhibition is altered. Finally, a complementary series of experiments will test the hypotheses that long-term potentiation/depression drive the alterations in synaptic dynamics found at the junction of deprived and spared cortex.

Amount: £400,414
Funder: The Wellcome Trust
Recipient: King's College London

Characterization of glycoproteins from the flagellar pocket and endocytic pathway and the role of actin in polarized traffic in African trypanosomes. 29 Jun 2006

African trypanosomes are protozoan parasites responsible for sleeping sickness in man and Nagana in cattle and represent a significant problem in sub-Saharan Africa. A long list of discoveries has also made these cells fashionable vehicles for biological research. Although these parasites are obligatorily dependent on the uptake of factors from their mammalian hosts, our understanding of the molecular machinery involved is very limited. Endocytosis in trypanosomes occurs at rates far higher than in any other cell but is entirely limited to a tiny area of the cell surface termed the flagellar pocket (FP). The basis of this sequestration and the high rate of endocytosis of receptors is unknown. Potentially, the endocytic machinery of the FP is an area of vulnerability for the trypanosome and represents an access point for therapeutic intervention. The aim of this proposal is to exploit new results reported by the applicant to advance this possibility. These new data suggests that N-glycans containing linear poly-N-acetyllactosamine (pNAL) might act as sorting signals in endocytosis in these cells and several objectives are proposed: First the presence of pNAL has allowed the specific purification of proteins from the FP/endocytic pathway using tomato lectin. This has solved a major technical problem in the field. A range of proteins from the FP/endocytic pathway have now been purified. Antibodies have been raised against these proteins (native and deglycosylated) and expression cloning of the genes is feasible. Second, it proposes to characterise the protein(s) in the FP interacting with the pNAL sorting signal. Third, attempts will be made to exploit insect or procyclic forms of the parasite, where receptor mediated endocytosis does not occur, to re-constitute elements of the bloodstream stage endocytic pathway. Overall, this proposal has the potential to shed new light on this exigent area of research.

Amount: £298,842
Funder: The Wellcome Trust
Recipient: Trinity College Dublin

Investigation of the humoral immune response to pneumococcal polysaccharides and the role of a conjugate pneumococcal vaccine in secondary prevention of invasive pneumococcal disease in HIV-infected Africans. 09 May 2006

Invasive pneumococcal disease (IPD) is the only important HIV-related problem in sub-Saharan Africa which is potentially vaccine preventable. Conservative estimates suggest 1 million cases of adult IPD occur annually in this region as a consequence of HIV-infection. In our recent efficacy trial in Uganda, the 23-valent pneumococcal polysaccharide vaccine (PPV) increased the risk of IPD/pneumonia. The efficacy and role of the newer conjugate pneumococcal vaccines (CPV) remains unknown. I aim to investigate potential mechanisms of vaccine failure and harm associated with the use of PPV, and assess the response to and efficacy of CPV in a randomised controlled trial. CPV will be used to probe for defects in serological response to polysaccharides in a) previous PPV vaccine recipients b) individuals with past IPD, to describe and categorise the prejudicial effects of exposure to vaccine-purified or natural polysaccharide. A double-blind, randomised placebo controlled trial of CPV as secondary prophylaxis to prevent recurrent IPD will be performed in HIV-infected Malawian adults. Proven efficacy of the vaccine as secondary prophylaxis will be a fair indicator of potential as primary prophylaxis. Initial studies of the B-cell mechanisms that underpin altered or deleterious serological response will commence with validation of appropriate and "field-friendly" methods for the isolation of polysaccharide responsive B-cells, for future molecular-based descriptions of B-cell populations and dynamics.

Amount: £58,552
Funder: The Wellcome Trust
Recipient: University of Liverpool

Ensembl: Current, complete and consistent annotation of large scale genome sequence. 26 Apr 2006

Ensembl will provide a data resource to enable the biological research community to use effectively the human genome sequence and other large genome sequences. By using a wide variety of automated methods and incorporating and/or linking to other data sources it will maintain an annotated version of genome sequence that stays up to date and is coupled to sequence search servers and maps. In particular, as far as possible, we aim to identify and annotate all genes. The data will be analysed using computational methods from many sources and will be integrated via a modular, documented Perl and Java object layer that accesses an underlying relational database. All data will be freely available via the web and bulk download, and software will be open source. We will coordinate closely with other public domain systematic annotation efforts in particular NCBI, supporting exchange of information and interchange of identifiers.

Amount: £4,050,872
Funder: The Wellcome Trust
Recipient: European Bioinformatics Institute

Cognitive and social processes in psychosis: developing more effective teatment approaches. 23 Jan 2006

The aim of our research is to advance the understanding of psychosis, in order to improve treatment. Schizophrenia-spectrum psychoses are distressing and disabling for sufferers, place high demands on carers and have high health and social care costs. The effectiveness of medication, the first line treatment, is limited and the risk of relapse is high. Our research strategy is to combine two major outcome trials of psychological treatments with a linked series of explanatory studies. We have developed and evaluated two treatments, cognitive behaviour therapy (CBT) and family interventions (FI). Both are known to be effective, but they have different targets of change and little is known about how they work. Our model of psychosis identifies specific cognitive and social processes which we hypothesise to maintain psychosis and to be important targets of treatment. We intend to test this model to improve understanding of change processes and enhance treatment effectiveness. After five years, we aim to have confirmed that CBT reduces relapse; to have identified processes which maintain psychosis and contribute to relapse; to have identified how CBT and FI work; and to have refined both treatments to meet specific clinical needs.

Amount: £55,000
Funder: The Wellcome Trust
Recipient: King's College London

MA Social History of Medicine. 30 Aug 2006

MA Social History of Medicine: The course is intended for students who wish to specialise in the Social History of Medicine, and to acquire the skills to carry out research in the field. Drawing in particular on the specialist areas of the course tutors, the MA aims to develop a broad historical knowledge of the subject, to develop methodological skills, to develop new topics for historical investigation, and to carry out primary research in the history of medicine. Core Course 1 : 'Outlines of Medical History' This is a compulsory course, intended to provide students with a broad chronological framework and outline of some of the main themes and developments in the social history of medicine, from the early modern period to the twentieth century. It focuses on the evolution of medical ideas, the structure of medical practice, medical institutions, and the scientific, demographic, cultural, and social context of medical intervention. Core Course 2 : 'Texts and Contexts in the History of Medicine' The secondary compulsory Core Course, is intended to give students a grounding in the wide range of sources available to the social historian of medicine, including practice records, local archives, diaries, public health material, health propaganda, patients' narratives, and visual sources: architecture, paintings, photography and film. Intensive use is made of primary source material and a 'hands on' approach, while contextualising the material within broader historical debates. Visits are made to the Modern Records Centre, Warwick Country Record Office and the Wellcome Trust Library.

Amount: £63,774
Funder: The Wellcome Trust
Recipient: University of Warwick

MA in Health, Medicine and Society: Historical and Contemporary Perspective. 30 Aug 2006

Master's Degree in the History of Medicine: Course title: MA in Health, Medicine and Society : Historical and Contemporary Perspectives. Within the specialist MA in the history of Medicine these comprise a core course, and two special subjects. In addition, within the broader MA Programme, there is either a seminar on themes and perspectives (full time students) or a dissertation forum (part time students). There are two core courses which are central to the research training of the student, and which are compulsory for all students. Core I (autumn term) 10 weeks. Themes and Problems in the History of Medicine; five selected case studies from antiquity to the present day, explored through primary and secondary sources. Core II (spring term for full time students, or summer term, Year 1 for part timers). Approaching your dissertation (i) methodology (5 weeks); (ii) sources in libraries and record offices (5 weeks). There is a selection designed for students on the MA programme as a whole. There are also special subjects and the time devoted in these subjects enables a detailed study to be undertaken. There is a rolling programme of special subjects, the current choices being: Darwinism and Eugenics, Madhouses, Mad-doctors and Madness in Britain, 1660-1900), Oxfordshire Local History Practitioners and Patients, 1850-1948 Science, Medicine and Society in France and England in the Eighteenth Century The Body and its History in Western Societies The Origins and Development of the NHS, 1919 to the present day. In addition to this specialist provision students are advantaged by incorporating two elements of the broader MA Programme in the Humanities within their specialist MA in Health, Medicine. These are the Dissertation Forum, and the full-time 'Themes and Perspectives' course.

Amount: £39,446
Funder: The Wellcome Trust
Recipient: Oxford Brookes University

MA in Medicine, Occupation and Health in Historical Perspective. 30 Aug 2006

University of Exeter: Master's Degree in the History of Medicine Course title: MA in Medicine, Occupation and Health in Historical Perspectives. This MA is the multi-disciplinary study of the role of modern medicine in the workplace in an international context. It integrates the history of medicine and medical practice with contemporary issues in occupational health. The one year programme is structured in the following way: (a) Historical Skills and Methodology, (b) A core course consisting of two specialist modules in the history of medicine and issues in occupational health. The optional modules include, but not limited to: Medicine and Social Policy in Modern Britain; Population; Disease and Health in Modern Britain; Sociology of Reproduction; The Sociology of Science and Technology; Nineteenth Century Science and Gender. (b) Fieldwork: Students may develop an individual fieldwork module in collaboration with staff. This will enable a student to combine professional and/or personal experience with an intellectual perspective on the historical development of their chosen area. Dissertation: individual topic of 20,000 words, agreed between individual students and the programme director. The course is delivered in Semesters 1 and 2, taken up with taught modules. The focus is on providing both a broad knowledge of issues in medical history and occupational health in the modern world and also the basic training in skills required for conducting research in medical history.

Amount: £19,823
Funder: The Wellcome Trust
Recipient: University of Exeter

X-ray crystallographic studies of malaria parasite proteins. 28 Mar 2006

Malaria is a widespread health problem and remains a major killer. Although a tremendous body of data exists on the biology of malaria, three-dimensional structure information on key parasite proteins is scant. I propose to set up a research operation within the International Centre for Genetic Engineering and Biotechnology, New Delhi directed at using X-ray crystallography to elucidate the atomic structure of key malaria proteins. An understanding of the structural principles underlying these proteins will be of pivotal importance in biological and therapeutic progress. The proposed X-ray crystallographic studies will form the core of a multi-disciplinary approach in which structural information feeds back into functional studies. Amongst the initial targets for over-expression, purification, and crystallisation are Pfg27 (sexual stage protein), TRAP (Thrombospondin related anonymous protein), and Duffy-Binding-like domains. All biochemical and most crystallographic experiments are expected to be conducted in New Delhi. Where necessary, crystallographic diffraction data will be collected at various international synchrotron facilities. The proposed work will be carried out using established methodologies in which I have considerable experience. These structure determinations will contribute fundamentally to malaria biology, and may facilitate development of new anti-malarials.