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Funders:
Paul Hamlyn Foundation
The Wellcome Trust
Recipients:
University of Leicester
Amounts:
£500 - £1,000

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Results

Understanding the origins of pathogenic IgA in IgA nephropathy. 27 Jun 2012

In IgA nephropathy (IgAN), serum and mesangial IgA is enriched for IgA1 molecules that are polymeric, display low antibody affinity and are poorly galactosylated at their hinge region. These features are typical of IgA normally produced at mucosal surfaces and this contrasts with that usually present in the systemic compartment. However, in IgAN, numbers of polymeric IgA1-producing plasma cells are reduced at mucosal sites and increased in systemic sites. This Fellowship will test the hypothesis that in patients withIgAN, polymeric, poorly galactosylated IgA1 is synthesised by a population of mucosally-primed IgA+ B cells which mis-traffic to the systemic circulation. I aim to identify the population of IgA+ B cells which produces poorly galactosylated polymeric IgA1 in patients with IgAN and healthy controls. I will use flow cytometry to isolate IgA+ plasmablasts and will carry out microarray analysis and Q-PRC to establish important cell phenotypes particularly relating to O-glycosyltransferase, J-chain expression and homing characteristics. I will immortalise specific cell populations to allow study

Amount: £224,061
Funder: The Wellcome Trust
Recipient: University of Leicester

A new approach to the treatment of invasive pneumococcal diseases 16 Jul 2012

Streptococcus pneumoniae causes a very high number of cases of pneumonia, meningitis and bacteraemia, worldwide. Despite using antibiotics that kill the bacterium, a large number of patients still die and in meningitis, many survivors have profound neurological handicap. This is because the bacterium produces a very damaging virulence factor that is not inhibited by antibiotics. This problem constitutes an unmet medical need that Professor Peter Andrew and colleagues from the University of Leicester are proposing to fulfill. They have identified that small molecules can inhibit this virulence factor and are effective in vivo. The team have been awarded funding through the Seeding Drug Discovery initiative to identify new small molecules and through a programme of medicinal chemistry, combined with in vitro and in vivo testing, to identify lead compounds with appropriate efficacy, pharmacokinetics and toxicology. The aim is that giving such molecules will reduce the number of patients that die or suffer handicap as a result.

Amount: £437,952
Funder: The Wellcome Trust
Recipient: University of Leicester

The role of mast cell and airway smooth muscle interactions in the pathophysiology of asthma. 31 May 2012

We hypothesise that airway hyperresponsiveness and persistent airflow obstruction in asthma result from a) intrinsic abnormalities in airway smooth muscle (ASM) from asthmatics and b) interactions between ASM-mast cells. We aim i) to examine the differences between ASM from asthmatics and non-asthmatics and to determine the mechanisms underlying these differences interms of calcium homeostasis using single cell and FLIPR analysis; contractility using collagen gel contraction assays and single c ell measurements of maximal contraction and velocity; synthetic capacity using a variety of approaches including ELISA, immunoblotting, proteomics, qPCR and gene array; migration using 2D assays; proliferation by MTS assay and thymidine incorporation; and survival by Annexin V and PI staining, ii) to investigate in vitro the effect of ASM-mast cell interactions on ASM and mast cell function respectively and to confirm effects, as appropriate, in tissue and iii) to confirm that localisation of ac tivated mast cells in the ASM-bundle is a feature of asthma across severity of disease and to determine whether this is affected by corticosteroids or experimental viral infection. For the in vitro experiments we shall use freshly isolated and primary ASM cultures from bronchial biopsies from asthmatics and controls and primary mastcells from lung resection material.

Amount: £329,341
Funder: The Wellcome Trust
Recipient: University of Leicester
Amount: £30,000
Funder: The Wellcome Trust
Recipient: University of Leicester

Medicine, computus and quadrivium in English manuscripts of the 11th and early12th centuries. 16 Apr 2012

This project forms part of a larger study of scientific and medical learning in England in the 11th and 12th centuries, focussing on the nexus between change in the mathematical sciences (quadrivium) and computus (time-reckoning), and change in medical science. In the 200 years straddling the Norman Conquest and the reception of Greco-Arabic learning, England was actively participating in new trends in both domains. Recent scholarship on medicine has confirmed England's openness to Salerno's "theoretical turn", but has neglected medical materials lodged in quadrivium/computus manuscripts, especially those written after 1100. My hypothesis is that reception of new medicine cannot be detached from reception of other kinds of scientific learning which share the same manuscript context. Two manuscripts written shortly around 1100, Durham Hunter 100 and Oxford St John's College 17, contain a distinctive mix of both old and new materials about both medicine and quadrivium/computus. This project aims to analyse the sources of their medical texts, and compare them to contemporary English manuscripts of similar character, in order to situate medical learning in a process of intellectual and cultural transition. It will result in an article, which will be expanded into a chapter in the projected monograph.

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

Biomedical Vacation Scholarship 25 Jun 2012

Not available

Amount: £10,080
Funder: The Wellcome Trust
Recipient: University of Leicester

The 1958 Birth Cohort Biomedical Resource - Facilitating access to data and samples and enhancing future utility. 20 Oct 2010

The 1958 Birth Cohort (1958BC) recruited 17,416 British newborns 3-9 March 1958. A BiomedicalResource (58BMR) was later created by the biomedical survey (Strachan, Power, Bynner[2002/3]) to include extensive questionnaire data, physical measures and biosamples on 1958BCparticipants. The biosamples, stored in ALSPAC laboratories at the University of Bristol, includeblood, urine and saliva (9,000+ participants), DNA (8000+), lymphoblastic cell lines (7,500+). Mostparticipants providing DNA have been genome-wide-genotyped (data held at European-Genome-Phenome-Archive). Other data are held at UK-Data-Archive, managed by Centre for LongitudinalStudies. The 58BMR is used widely by biomedical, social and population scientists nationally andworldwide. 58FORWARDS will maintain and develop the infrastructure for managing, linking andreleasing biosamples/data from 58BMR, facilitating scientific exploitation by makingbiosamples/data readily available for sharing. 58FORWARDS has three aims: (1) Fund andsupport pre-existing procedures and systems that have underpinned the 58BMR for >10 years; (2)Ensure targeted development of key systems and procedures to meet rapid, and understandable,changes in the strategy of national funders regarding infrastructural support for major UK cohorts;(3) Ensure that access to data and biosamples from the 58BMR remains streamlined and securethrough all maintenance and development work.

Amount: £625,808
Funder: The Wellcome Trust
Recipient: University of Leicester

An Anaerobic Crystallisation Facility at the University of Leicester. 09 Mar 2011

We propose to establish a new facility for anaerobic protein crystallisation and single crystal micro-spectrophotometry at Leicester. This facility will be critical to developing new research strategies to enable us to explore protein mechanisms within three major biological areas of interest at Leicester (many of which are WT funded): (i) Regulation of gene expression (ii) Redox enzymology of important iron-dependent enzymes (iii) Key enzymes of pathogenic microorganisms. This integrated, multi disciplinary facility will be a significant advance; it will have multiple users within Leicester and will be made available to others, since such facilities are not accessible elsewhere. The technical expertise that is needed to support this new facility is already available on-site and the new facility will form part of the on-going, long-term investment in structural biology at Leicester.

Amount: £107,562
Funder: The Wellcome Trust
Recipient: University of Leicester

Harnessing the Power of the Criminal Corpse. 09 Mar 2011

This programme brings together six interdisciplinary research strands overseen by four senior scholars with proven track records that will together produce a core history of the use and power of the criminal corpse between the late seventeenth and the mid-nineteenth centuries. The criminal corpse featured prominently in popular culture, as well as science, civic life, and medico-legal productions, and its power was harnessed for the purposes of negotiating social relationships of class, the powe r of medical men and the judiciary, and in the creation of popular and scientific medicine. Such bodies were historically significant sites of overlapping, competing, and often contradictory, understandings of human anatomy, criminal justice, popular medicine, and the social geography of the body. A broad interdisciplinary study of the use, meanings and power of the criminal corpse in Britain can be used as a vehicle for methodological and substantive advances in approaches to the wider history of the body. Additional context comes from studies of the criminal corpse in the popular imagination and its role in the development of normative ethics. An ambitious list of academic and popular outputs, including books articles and an online exhibition, ensures value for money.

Amount: £945,389
Funder: The Wellcome Trust
Recipient: University of Leicester

Open access award. 20 Sep 2011

Not available

Amount: £60,000
Funder: The Wellcome Trust
Recipient: University of Leicester

Women Surgeons in Britain, 1860-1918. 08 Jun 2011

This project has a dual intention. Firstly, to examine the cultural, social and self-representation of the woman surgeon from the second half of the nineteenth century until the end of the Great War; and, secondly, to investigate precisely what surgery women actually performed during this period. In doing so, I aim to bring together and expand upon work on the history of women in medicine (particularly that by Mary Ann Elston), the history of surgery (Christopher Lawrence; Peter Stanley; Sally W ilde), and feminist historical studies concerning women's place in Victorian and Edwardian society (Philippa Levine; Anne Witz), in order to offer a new perspective on the questions provoked by medical women. By utilising a wide variety of sources, including visual representations of female surgeons and a wealth of unpublished material, such as hospital records, case notes, and correspondence, I intend to provide a wide-ranging history of women surgeons and their social, political and medical im pact between 1860 and 1918.

Amount: £108,343
Funder: The Wellcome Trust
Recipient: University of Leicester

Commercial use of tissue samples in the 1958 birth cohort: A study of participants' views 31 Aug 2011

To characterise the views of a sample of participants in the 1958 Birth Cohort on possible commercial uses of donated blood samples and to consider the legitimacy and legality of allowing such use within the terms of the original consent. More specifically, the aims of study are: To explore participants' understandings of the statements in the 1958 birth cohort information sheets to the effect that 'samples will be used for non-commercial research purposes only' and that use will be for 'future medical studies'. To identify whether participants' views are likely to vary depending on the type of commercial use proposed or the type of organisation seeking access to the resource;Explore participants' views on the value of creating a Participants' Panel to provide a forum for consulting participants on ethical,legal and scientific issues in the future To explore participants' understandings of the statements in the 1958 birth cohort consent documentation to the effect that information and samples will be used solely 'for use in future medical research studies of the causes, diagnosis, treatment or outcome of disease'. Identify a range of other commercial use clauses or principles seen as "protective" or "restrictive" or "useful compromises" by cohort owners, RECs, and industry, and explore participants? views of these To consider whether commercial access might be tolerated and lawfully granted under the existing consent and/or whether a reconsent procedure would be required for commercial use. Consult with a small number of key stakeholders, including Research Ethics Committees, the UKBB Ethics and Governance Council, and a small number of commercial firms to identify any further challenges or questions in relation to possible commercial use of tissue.

Amount: £19,886
Funder: The Wellcome Trust
Recipient: University of Leicester

Receptor tyrosine kinase regulation of mast cell-airway smooth muscle beta2-adrenoceptor function in asthma. 15 Mar 2011

Beta2-adrenoceptor agonists form a cornerstone of asthma treatment by reversing and/or preventing bronchoconstriction. However, in some subjects beta2-adrenoceptor agonists are of poor efficacy, particularly during acute exacerbations, and regular use may lead to deterioration in asthma control. The mechanisms are poorly understood. Mast cell infiltration of the airway smooth muscle (ASM) in asthma is a characteristic feature of the asthmatic phenotype. Mast cells interact intimately with ASM th rough bi-directional cell-cell and mediator-dependent effects. Interestingly, human lung mast cell (HLMC) beta2-adrenoceptor responses are attenuated within minutes of exposure to stem cell factor due to beta2-adrenoceptor phosphorylation on Tyr350 and receptor internalisation. We hypothesise that mast cell-ASM cross-talk leads to beta2-adrenoceptor uncoupling in both cell types through receptor tyrosine kinase activity. If true, targeting these pathways may enhance beta2-agonist efficacy and sa fety in asthma. We will test this hypothesis by investigating: 1. The ability of HLMC and ASM-derived growth factors to phosphorylate and uncouple beta2-adrenoceptor agonist responses in these cells. 2. The ability of ASM in co-culture with HLMC to inhibit HLMC beta2-adrenoceptor agonist responses, and vice versa. 3. Expression of phosphorylated beta2-adrenoceptors in bronchial biopsies from subjects with asthma compared to healthy controls, and their correlation with clinical measurements .

Amount: £162,905
Funder: The Wellcome Trust
Recipient: University of Leicester

A Coming of Age Story: A History of the Indian Pharmaceutical Industry, 1905-1966. 13 Jan 2011

The project will analyse the history of the pharmaceutical industry and its economic and social impact in colonial and post-colonial India. Several pharmaceutical companies were established in India from 1900 onwards, including Alembic Chemicals (1907), Zandu Limited (1910), Bombay,M/s Dharamsi Morarji Chemical Co, Bombay, M/s Bhogilal Premchand and Co, Bombay. The burgeoning market for drugs also attracted Multi-National Companies such as Glaxo, Wellcome Burroughs,and Unilever. It will combi ne history of medicine with business history to highlight how the use of modern pharmaceuticals and their markets were established in modern India. It will examine nationalist enterprise, urbanisation, and the patronage extended to the drugs and pharmaceutical industry by the princely state of Baroda and the colonial government. It will examine the role of the Indian pharmaceutical industry and the colonial state in shaping and standardizing the cultures of medical consumption in India Fi nally the project will locate the expansion of the Indian pharmaceutical industry as representative of India s pursuit of self-sufficiency in primary and secondary industrial goods in the post-independence era. In summary the project will provide a comprehensive analysis of the pharmaceutical industry in India to further the historical links between colonialism, economic nationalism, and modern medicine in India.

Amount: £171,087
Funder: The Wellcome Trust
Recipient: University of Leicester

Seeding Drug Discovery: projects we've funded Therapeutics Alpha-GABa receptor modulators for the treatment of cognitive impairment associated with Huntington’s disease Huntington's disease is a fatal genetic disease characterised by a movement disorder that is accompanied by a decline in cognitive function and changes in mood and behaviour. The decline in cognitive function may precede the movement disorder by a decade or more and is a very important component of the functional disability assoc 06 Jun 2011

Streptococcus pneumoniae causes a very high number of cases of pneumonia, meningitis and bacteraemia, worldwide. Despite using antibiotics that kill the bacterium, a large number of patients still die and in meningitis, many survivors have profound neurological handicap. This is because the bacterium produces a very damaging virulence factor that is not inhibited by antibiotics. This problem constitutes an unmet medical need that Professor Peter Andrew and colleagues from the University of Leicester are proposing to fulfill. They have identified that small molecules can inhibit this virulence factor and are effective in vivo. The team have been awarded funding through the Seeding Drug Discovery initiative to identify new small molecules and through a programme of medicinal chemistry, combined with in vitro and in vivo testing, to identify lead compounds with appropriate efficacy, pharmacokinetics and toxicology. The aim is that giving such molecules will reduce the number of patients that die or suffer handicap as a result.

Amount: £1,029,222
Funder: The Wellcome Trust
Recipient: University of Leicester

Blood transfusion, medicine and identity in the USA, Britain and Russia 1945-2010 20 May 2011

The proposed project will examine how the use of blood in medicine has been received, understood, and challenged, both popularly and politically, since 1945, and what this reveals about changing notions of blood and identity in three different countries. The bloodshed of World War II led to rapid advances in blood storage, preservation and transfusion in the USA, Britain and the Soviet Union. In each country, these medical developments served to sharpen existing debates about blood and key identifiers such as race, class, sexuality and religion. The appeals, campaigns and representations for (and against) the use of blood in medicine which stemmed from identity are the subject of this research project. This has a resonance beyond the medical community as particular interpretations of blood and medicine influence mainstream medical practices and healthcare provision and thus the treatment of the population at large. The exploration of debates about blood in these three contexts offers insights into the way medical advances are received and how reception influences policy across cultures. The key goals include the publication of articles for medical practitioners (in English and in Russian) and for a scholarly journal.

Amount: £4,998
Funder: The Wellcome Trust
Recipient: University of Leicester

"The drama of medicine" to be held at the University of Leicester on 11-13 July 2011 30 Nov 2010

To explore the breadth and depth of the interface between medical practice, medical education and teaching and research within the Arts and humanities. To disseminate information about current: and recently , concluded research and teaching initiatives within the medical humanities field of enquiry. To provide stimulus for new ideas and activity within the medical humanities field, and to provide debate within these, by means of keynote speakers and invited workshops for conference delegates to participate in. To strengthen further the associations and networks between teachers and researchers from different academic centres or outside these, both nationally and internationally. To provide a forum for medical and arts/humanities students at the undergraduate level to showcase their work and share ideas (through a linked but separate student conference). To engage lay organizations which share an interest in this field of enquiry.

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

Biomedical Vacation Scholarships 20 May 2011

Not available

Amount: £11,520
Funder: The Wellcome Trust
Recipient: University of Leicester

Open access award. 21 Sep 2010

Not available

Amount: £60,000
Funder: The Wellcome Trust
Recipient: University of Leicester