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Results

Development of a type B lantibiotic for treatment of Clostridium difficile infection 16 Sep 2008

C. difficile infection (CDI) has increased in incidence and severity through the last decade to become the major cause of mortality amongst nosocomial infections. Currently, there are very few therapeutic options for CDI and recurrence of disease after initial successful therapy is a major health problem and burden to healthcare systems.

Amount: £3,500,000
Funder: The Wellcome Trust
Recipient: Novacta Biosystems Ltd

Integrating infection prevention into health care delivery. 16 Sep 2008

Health : This application is focused on applied research in infection to prevent healthcare associated infection in the NHS, improve clinical outcomes and patient safety. This is addressed through a comprehensive programme of four workstreams that work from an organisational level and the adoption of innovation through to prevent infection through applied molecular epidemiology and pathogenesis to development and application of epidemiological data and tools in the context of multi-disciplinary capacity planning and training. Wealth: The innovations developed are all directed at reducing health care acquired infections which are a major cost to the NHS. There are potential major cost savings and reduction of bed days per patient. Better use of existing data sources will identify information required to produce financial savings without the need for new data collection programmes. There is scope for wealth generation if new diagnostic tests are generated or targets for vaccines or therapies identified.

Amount: £200,000
Funder: The Wellcome Trust
Recipient: Imperial College London

Modernising Medical Microbiology: Establishing how new technologies can be optimally integrated into microbiology. 16 Sep 2008

This proposal should lead to a comprehensive web-based tool managed by the HPA which microbiologists in NHS Trusts could use to harness genomics in optimising management of local infection control and halting transmission of major pathogens. It will also provide a data/sample repository which national researchers could exploit, in conjunction with those at the cutting edge of bioinformatics, to elucidate host pathogen interactions and thus identify future targets for medical or strategic interventions. The programme of work will produce more complete descriptions of routes of pathogen transmission, which will lead to improvements in current guidelines for infection control. In terms of leadership and training, the Consortium will mature a group of young researchers excited about the genomic revolution, who have seen the techniques applied successfully and are now ready and want to go and do it themselves. These individuals will be key future leaders in microbiology and infectious diseases.

Amount: £2,829,138
Funder: The Wellcome Trust
Recipient: University of Oxford

Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer). 16 Sep 2008

To develop effective interventions to improve population health requires a much greater understanding of what works, why, for whom and in what circumstances. This will necessitate the development of epidemiologically and social scientifically Informed complex and multi-factorial interventions that are effective across settings and behaviours; the rigorous evaluation of complex interventions, often using pragmatic controlled trial designs with nested process evaluation and including natural experiments of new policy programmes and the use of routine data to develop and target interventions and to provide sources of data on contexts and long term outcomes for intervention studies. The centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer) brings together team of world class researchers with expertise in a wide variety of quantitative and qualitative evaluation methods and intervention technologies to address these issues. Building on a strong track record, along with partners from public health policy and practice, and the public we will develop, test, evaluate and then implement interventions that are effective in improving the health of the population across settings and behaviours and which address health inequalities, with a particular focus on children and young people. We will also provide high quality training programmes to develop skills of public health researchers

Amount: £1,949,756
Funder: The Wellcome Trust
Recipient: Cardiff University

Extension to grant 081552/Z/06/Z 'My illness': a series of 5 x 30 minute films for use on TV, Broadband & DVD. 17 Oct 2007

'My Illness' is a series of 5 x 30-minute films about common conditions such as asthma, psychosis (schizophrenia and bipolar disorder), cystic fibrosis, leukaemia and multiple sclerosis. Each film will focus on one individual who will find out the latest scientific thinking on the cause (or causes) of their condition by meeting reseachers and clinicians using state-of-the-art diagnostic equipment and imaging. The emotional impact of living with the illness will be explored through meeting others with the same condition and by experiencing a piece of art on the subject such as photography, dance, poetry, the visual arts or drama. Some of these artworks will be existing Wellcome-funded projects.

Amount: £4,975
Funder: The Wellcome Trust
Recipient: Media Trust Productions

Clore Leadership Programme extension 2008/2009 16 Jan 2008

The Clore Leadership Programme :Developing Leaders in the field of Arts and Science The Clore Leadership Programme is an initiative of the Clore Duffield Foundation and aims to develop the skills and experience of leaders across a wide range of different creative and cultural activities, including those providing a link between the arts and biomedical science. The priorities of the Clore Duffield Foundation are education, the arts, cultural leadership training, health and social welfare. The Foundation is governed by a Board of Trustees chaired by Dame Vivien Duffield DBE, who also sits on the Clore Leadership Programme Management Committee. The Foundation is a registered charity. The Clore Leadership Programme is seeking £35,000 a year for two years to develop potential leaders in the field of cultural activity - with a particular emphasis on those interested and involved in the interaction of the arts and science - through an intensive modular Fellowship programme. The funding will provide for one full Fellowship for each of the two years of 2005-6 and 2006-7.

Amount: £70,000
Funder: The Wellcome Trust
Recipient: Clore Leadership Programme

'Endless Forms': Charles Darwin, Natural Science and the Visual Arts' 16 Sep 2008

The project aims to: - Investigate Darwin's influence on 19th century art, which had been little examined until now. - Illuminate the interplay of natural science and forms of visual expression in the 19th century. - Participate in a highly innovative way in the international celebrations of Darwin's birth, including Darwin 200 and the Cambridge Darwin 2009 Festival, and mark his links with Cambridge, and the Fitzwilliam Museum in particular. - Project the originality of the approach so as to intrigue, excite and provoke debate among people of all ages and walks of life. - Ensure that Darwin's achievement and the impact of his ideas are better understood by a wide audience. - Challenge the notion of Darwin (to an extent propagated by Darwin himself) as inartistic, and devoid of a sense of beauty. - Highlight the social, cultural and ethical issues arising from popular understanding/reception (or, often, misunderstanding) of Darwin's ideas and how this was projected by the artistic imagination. - Using the exhibition as a catalyst, make clear the continuing relevance of the legacies of Darwin's scientific theories to a wide contemporary audience, through public programmes (workshops, talks, debates, and outreach activities outside the museum, and talks by specialists in other museums and research centres) and in audioguide and website/IT resources. - Emphasise the interdisciplinary nature of the project by inviting a range of authoritative voices from different disciplines to comment on ideas, themes and works of art represented in the exhibition, in particular scientists and historians. - Invite those with an existing interest in the arts to engage more actively with the scientific and biomedical questions arising from the project and those with a primary interest in the sciences to attain a fresh perspective on the wider social, cultural and artistic impact of scientific discovery. - Establish a unique working partnership with the rich seam of Darwinists, scientists, historians of science and those with responsibility for Darwin resources working in the local academic and other research communities. - Recognise and monitor the ambitious nature of the project by conducting focus group studies as part of on-going formative evaluation. - Attract in the region of 75,000 local, national and international visitors. - Build long-term partnerships with scientific and other scholarly communities already involved in the project at local and national level, from specialist academics to journalists. - Ensure widespread media coverage, through the implementation of a Marketing and Communications strategy already in place and on-going

Amount: £204,898
Funder: The Wellcome Trust
Recipient: University of Cambridge

The collector as consumer in eighteenth century Britain: Dr William Hunter (1718-1783) 16 Jun 2008

This research project aims to enhance the work that I have already completed on Dr William Hunter's lectures on Anatomy to students at the Royal Academy of Arts. The specific purpose of this paper is to identify and convey a particular 18th century aesthetic that valued the role of the craftsman/woman in the fine arts and is discernible in Hunter's teaching at the RA and in his production and display of anatomical specimens. However, this is also part of a wider project that forms a chapter in my PhD thesis: Dr William Hunter and the British School of Artists.

Amount: £479
Funder: The Wellcome Trust
Recipient: University of Glasgow

Student Elective Prize for Mr Fatou Mama Manneh. 29 Aug 2008

To determine the incidence of hypertension amongst patients that I encounter and to perform ECG on them to determine the incidence of left ventricular hypertrophy in the patient group. A sample of patients from urban and rural settings will be examined.

Amount: £1,050
Funder: The Wellcome Trust
Recipient: Queen Mary University of London

Expression analysis of Elf5 transcription factor during Skin development, regeneration and wound repair 27 Apr 2017

Normal skin development and homeostasis are fundamental to survival and health of individuals. The skin is a highly tractable model system to explore functionally the capacity of self-renewal, specification and differentiation underlying tissue development, regeneration and wound biology. E74-like factor 5 (Elf5) is a critical regulator of cell fate for several tissues. Elf5 has been described previously, to being expressed in the inner root sheath of the hair follicles. However, there is still a significant lack in the knowledge and understanding of Elf5 expression and function during skin/hair follicle development, regeneration and wound repair. Aim: The aim of this project is to determine the expression pattern of Elf5 during normal skin and hair follicle development, regeneration and wound repair. Objectives and Methods: i) during distinct days of skin development and hair-cycle associated skin remodelling and ii) wound repair by real time PCR and Immunohistochemistry staining. iii) identification of potential miRNA regulators of Elf5 in the skin. Outcome: Elucidating these molecular mechanisms is essential for understanding the basic principles of animal development. This will lead to new knowledge of the mechanisms involved in skin homeostasis and skin repair, which is of critical importance for human health.

Amount: £0
Funder: The Wellcome Trust
Recipient: Nottingham Trent University

The Role of Epstein-Barr Virus in Mycosis Fungoides 27 Apr 2017

Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma, a group of T cell cancers that generally affect the skin. Lesions/plaques arise in MF patients due to clonal expansion of epidermis-homing memory CD4+ T cell populations and the inflammation that accompanies this expansion. While the underlying cause of MF remains unknown, there is a strong association in a subset of MF with the common herpesvirus Epstein-Barr virus (EBV). The aim of this project is to investigate the impact of EBV on the phenotype and function of transformed CD4+ T cells isolated from skin lesions of MF patients. EBV positivity will be confirmed by qPCR of MF lesions. In cases which are EBV-positive, immune cells will be recovered from skin biopsies by mechanical and/or enzymatic digestion. Fluorescence in situ hybridisation (FISH) will be used to detect EBV-encoded small RNAs (EBERs) inside CD4+ T cells. This, in combination with staining for markers that identify CD4+ T cell subsets (naïve vs memory, cytotoxic, Treg, amongst others) will reveal the phenotype of the transformed cells. Finally, we will test the susceptibility of the isolated tumour cells to novel chemotherapeutic drugs and small molecule inhibitors.

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

Single molecule analysis of DNA bending by the human mitochondrial transcription factor A (TFAM) 27 Apr 2017

Visualization of the dynamics of transcription initiation by mitochondrial RNA polymerase in real-time performed at single-molecule resolution forms the basis of this proposal. The human mitochondrial transcription factor A (TFAM) carries out DNA bending and my aim is to investigate whether this is an essential feature for transcription initiation by mitochondrial RNA polymerase. Multi-colour single-molecule super-resolution microscopy is the technique which will be used to demonstrate whether this DNA bending phenomenon is required for transcription initiation. This is a high-throughput technology capable of visualising reactions at single-molecule level, especially transcription factor binding, DNA bending and production of RNA. This state-of the-art instrument makes use of three different colours for accurate detection; green and red for smFRET and blue for RNA. I am also intrigued and have a desire to investigate for the first time whether DNA bending by TFAM is correlated with transcription by mtRNAP molecules.

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

The effect of opioid receptor drugs on astrocyte function 27 Apr 2017

Astrocytes are multifunctional cells of the central nervous system that play key roles in development, homeostasis, neuromodulation, and inflammation. In recent years, the roles played by astrocytes in the development of chronic pain have received increased scrutiny. Evidence that astrocytes can contribute to the sensitization of neuronal circuits linked to nociception has led to renewed interest in the potential of astrocytes as a therapeutic target for intervention in chronic pain. Morphine remains the most effective treatment for pain, despite decades of research into alternatives. Despite this, very little is known of the effect of opiates on astrocyte function, or even whether astrocytes in the spinal cord express functional opioid receptors. The goals of this project are to address this gap in knowledge, by testing for the expression of mu-opioid receptors in astrocytes cultured from the spinal cord. Through both direct labelling for the receptor, and by testing receptor agonists and antagonists for activity in calcium and cyclic AMP signalling pathways, we will determine whether functional receptors are present in the cells. Success in these goals will illuminate whether opiates may act in part via modulation of astrocyte function, and whether this may contribute to analgesic effects.

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

IDENTIFICATION OF THE GINSENOSIDE BINDING POCKET ON THE P2X7 RECEPTOR: TOWARDS THE DEVELOPMENT OF AGENTS TO ENHANCE MICROBIAL KILLING 27 Apr 2017

The emergence of resistant prevalent bacteria as Mycobacterium tuberculosis, is boosting the development of novel strategies different to direct anti-microbial killing (antibiotics). An attractive approach is stimulating the immune system response to pathogens exploiting the existing pathways to deal with infection. This needs understanding of the mechanisms, for the development of novel modulators capable of boosting immune responses. P2X7 ion channels regulate immune responses, and activation on infected macrophages with ATP induces killing of Mycobacterium tuberculosis. Ginsenosides, known for their key role in the beneficial effects of immune system stimulation by ginseng, have been demonstrated by our collaborator, Dr Leanne Stokes, to be positive allosteric modulators of the P2X7 channel. Her research has shown the potential of enhancing P2X7 response with ginsenosides to increase microbial killing in macrophages. In this project, we will reveal the location and structural details of the binding pocket in P2X7 specific for ginsenosides of the protopanaxadiol series (Rb1, Rd, Rh2, and CK). We will use protein-ligand docking calculations on human P2X7 to predict the binding location and mode of the ligands, and molecular dynamics simulations to assess the dynamic stability of the complexes. This project will complement further NMR studies on P2X7/ginsenoside interactions.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of East Anglia

Purification of membrane transporters to identify topology and binding sites by mass spectrometry 27 Apr 2017

Understanding how membrane transport proteins interact with their substrates is a pressing challenge in biomedical research. In particular, multidrug pumps, which have a very broad substrate specificity, have continued to defy researchers by stubbornly withholding the secrets of their polyspecificity. In this project, the student (Michaela Kompauerova) will instigate a new avenue of research for our group that in the longer-term would enable us to tackle this problem using mass spectrometry. She will express and purify two bacterial ATP binding cassette transporters that show broad substrate specificity (indeed both Sav1866 and BmrA are multidrug pumps), s proof of principle for this approach. Having purified the transporters by the use of novel styrene maleic acid copolymer extraction she will investigate whether these proteins can be identified by mass spectrometry, enabling us to drive forward a new collaboration with protein labelling and mass spectrometry experts in Life Sciences and Chemistry. The longer-term aim of this collaboration is to develop new strategies for determination of membrane protein:substrate interaction surfaces.

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

Microtubule organisation and role of LL5-beta in lymphoid stromal fibroblasts 27 Apr 2017

The lymph node is a meeting point for lymphocytes with antigen-presenting cells, and rapidly expands during immune responses. Lymph node structure is highly compartmentalised, and the complex internal architecture is maintained during lymph node expansion. Therefore, mechanisms must exist to balance lymph node integrity with the need to remodel very rapidly. Fibroblastic reticular cells (FRCs) are the most abundant lymphoid stromal cell population, and span the full volume of the tissue. They provide structural support and are highly contractile. FRCs ensheathes bundles of extracellular matrix, termed the conduit, which filters draining lymph. The Acton lab works to understand how lymph nodes are remodeled during expansion and has shown that interaction between FRCs and dendritic cells change FRC behaviour. This project asks how the microtubule networks within FRCs are reorganised as the FRC network expands. Phosphoproteomic screening has revealed that LL5-beta, a protein targetting microtubules to adhesion sites is regulated by interactions between FRCs and dendritic cells. This may provide a mechanism by which FRCs uncouple from underlying matrix, and target secretion of proteases or new matrix to the expanding network. This project will investigate whether LL5-beta coordinates organization of microtubules in FRCs and whether dendritic cell contact changes LL5-beta activity.

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

Early Irish female medical graduates, 1872-1922 27 May 2008

The primary aim of my project is to illuminate the history of the first women to qualify in medicine in Ireland in the late nineteenth and early twentieth centuries. The first female medical graduates in Ireland qualified with medical licences in 1877 from the King's and Queen's College of Physicians of Ireland, with the first 'lady' medical students matriculating at an Irish university (Queen's College Belfast) in 1889. I have chosen to begin the project in the early 1870s in order to examine the attitudes of the medical profession towards women entering the medical profession and analyse the discussions that led up to the opening of medical examinations to Irish women.

A study of nurses' work with patients suffering from life-threatening infection 1919-1939. 31 Jan 2008

There is a group of elderly people who nursed prior to the antibiotic era and the opportunity to collect their memories of nursing in this period will be lost if no action is taken in the next few years. Persons aged 18 in 1939 will be 89 in 2007. The documentary evidence so far identified offers little insight into the "how and experiences" of nursing care delivery in the pre-antibiotic era. The opportunity exists to capture oral histories for the decade before 1939. Additionally, some documentary evidence exists through diaries, journals of the time and other written records - The RCN Archives catalogue identifies some potential sources from this period. Of interest are the skills and approaches used by nurses in the period 1919-1939 for managing the seriously infected patient. The study will focus on nursing the patient with an infection as secondary to, or as a complication of, hospitalisation. Inevitably, management of the infection would require the nurse to take account of the potential for cross infection.

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

Development of a simple rapid test kit for the early diagnosis of enterpatogenic Escherichia coli (EPEC) in children with diarrhoea 23 Nov 2007

Translation award support has been given to Professor Peter Williams and Dr Uta Praekelt to develop a rapid EPEC diagnostic kit for use in health centres in developing countries where resources and personnel are limited. By testing all children with diarrhoea, those with EPEC can be identified quickly and subsequently receive appropriate treatment, reducing the likelihood of long lasting clinical complications.

Amount: £423,290
Funder: The Wellcome Trust
Recipient: University of Leicester

Optimisation and testing of high affinity, selective, phosphate binding materials with biomedical applications 16 Jan 2008

Excess phosphate anions build up in the blood of patients with end-stage renal failure, leading to the condition hyperphosphatemia, a condition which, if untreated, can lead to serious side effects - in some cases fatal. In previous studies, we have developed high affinity phosphate receptors which operate in biologically relevant conditions. This proposal targets the continued development of these high affinity phosphate binders, and aims to convert them into phosphate binding polymers. We will then illustrate the relevance of these materials for the treatment of hyperphosphatemia using a series of in vitro and in vivo studies. In this new proposal we intend to: Develop useful crosslinked polymeric materials with high phosphate affinity - different phosphate binding monomers, crosslinkers and co-monomers will be used in order to generate a range of materials, Determine the ability of the different polymers developed above to bind phosphate under biologically relevant conditions (in vitro) - simple phosphate uptake experiments and assays will be performed. To use the results from parts 1 and 2 to further optimize the phosphate binding polymeric materials. To test the final optimized phosphate binding polymers in vivo. The effect of the polymers on phosphate uptake will be monitored in healthy rats in order to find the best candidate for therapeutic use. This candidate polymer will then be tested in nephrectomised rats, which are a useful model system for patients with kidney failure. This study will lead to therapeutically useful phosphate binding polymers, and sufficient data will have been generated that commercialisation of these materials will be a serious possibility. Commercial development will occur either by setting up a spin-off company, or by licensing the technology to one of the companies currently active in developing this type of therapy

Amount: £49,993
Funder: The Wellcome Trust
Recipient: University of York