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Results

University of Southampton MSc Global Health 11 Jul 2018

In an increasingly interdependent world, complex health problems require solutions that transcend geographic boundaries and draw on international and multidisciplinary collaboration to develop innovative responses. The MSc in Global Health within the School of Social Science at Southampton University is a multi-disciplinary programme designed to equip students with the necessary skills to understand and respond to global health challenges. Taught by research-active academic experts from multidisciplinary backgrounds, it includes core modules which provide students with a comprehensive understanding of key issues and concepts in transnational health. In addition the course has a strong quantitative component, which provides students with a robust understanding of statistical and epidemiological methods. A further feature is that students are able to choose from a range of optional modules offered by the Schools of Social Science (which includes social statistics, demography and gerontology), Geography and Law, as well as the Faculties of Medicine and Health Sciences in order to tailor their programme to meet their specific needs and interest. While not exclusively designed for those planning a research career, a significant proportion of former students have successfully chosen or continued on this path and currently work for academic institutions or research departments within governmental bodies.

Amount: £84,405
Funder: The Wellcome Trust
Recipient: University of Southampton

Facilitating ethical preparedness in genomic medicine 25 Jul 2017

This collaborative research programme will combine empirical bioethical research, conceptual, and theoretical analysis to examine the issue of ethical preparedness in the context of genomic medicine, and to inform and develop relevant policies for practice. We will conduct our research as genomic approaches to diagnosis and treatment, such as the 100,000 genome project, become embedded within health care. We will focus on the extent to which professionals are prepared for navigating the ethical issues within the new working environment of clinical genomics; one where research and clinical practice are more co-dependent than in the past, and where responsibilities of care, both to one person over time as well as to their current and future relatives are changing. The programme will utilise a range of research methods across a variety of settings to map the experience of practitioners, patients and participants in genomic medicine, the ethical issues they confront, and the impact on practice when these are challenging of their established practice, be that at the stage of recruitment/ introduction, diagnosis (or lack of), treatment, surveillance, longer term contact or need for contact of other .

Amount: £537,165
Funder: The Wellcome Trust
Recipient: University of Southampton

Understanding the formation of Pseudomonas aeruginosa biofilms in urinary catheters 31 May 2018

This proposal uses advanced microscopy and molecular techniques to examine the role of alginate in the attachment of Pseudomonas aeruginosa, and subsequent biofilm formation, on urinary catheters. There is an urgent clinical need for improved catheter management and the development of anti-biofilm materials, however approaches to date have failed and a lack of understanding of biofilm development may contribute to this. In this work, we intend using a simple laboratory model system to generate biofilms on urinary catheters, which can be tracked directly over time using episcopic differential interference contrast microscopy. Transposon mutants (obtained from the PA Two Allele Library) will be used and compared to the type strain, PAO1. In addition, Gibson Assembly will be used to generate knockout mutants for the same genes. The biofilm forming capability of each mutant and type (transposon vs knockout) will be assessed and compared. Transposon mutants have the potential to still produce peptides, with unknown form and function. Such peptides could affect biofilm development. In contrast, knockout mutants remove the target gene sequence. This project will provide information on general biofilm development, the role of alginate, and also indicate whether knockout mutants should be used for understanding the role of specific genes.

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

Open Access Award 2017/18 30 Sep 2018

Not available

Amount: £7,956
Funder: The Wellcome Trust
Recipient: University of Southampton

Open access publishing costs 2014/15. 15 Sep 2014

Not available

Amount: £11,371
Funder: The Wellcome Trust
Recipient: University of Southampton

Investigating bacterial transporters that convey antibiotic resistance 27 Apr 2017

The rise of antimicrobial resistance (AMR) threatens many of the major advances in modern healthcare as the treatments rely on the implicit ability of the antibiotic to allow the body to heal from a serious infection. Antibiotic efflux transport is central to the development of AMR. At the single cell level, it is becoming apparent that the use of efflux pumps is the first line of defence against an antibiotic. These pumps decrease the intracellular level of antibiotic while the cell activates the various other levels of protection. This frontline of defence involves a coordinated network of efflux transporters. In the future, inhibition of this efflux transporter network, as a target for novel antibiotic therapy, will require the isolation and then biochemical/biophysical characterisation of each pump against all known and new antibiotics. This depth of knowledge is required so that we can fully understand and tackle the mechanisms of developing antimicrobial resistance. The key goals of this project are to over-express, IMAC purify a hexahistidine-tagged versions of a number of the efflux transporter and then characterise ligand binding against a set of clinically relevant antibiotics. The method used to measure ligand binding is thermophoresis (Nonotemper, Monolith).

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

How does Serum Amyloid-P component contribute to the cognitive impairment observed in Alzheimer’s Disease? 27 Apr 2017

The neuropathology of Alzheimers Disease (AD) is associated with the formation of insoluble amyloid deposits containing fibres of amyloid-beta and tau protein. Despite this some patients exhibit high amyloid load yet little loss in cognitive performance. Recent studies have shown particular polymorphs of amyloid beta fibres are correlated with AD phenotypes, raising the possibility that factors that influence the dominant polymorph formed may determine the level of cognitive impairment experienced by the AD patient. Comparison of patients exhibiting similar amyloid load but significantly different cognitive outcomes have revealed that poor cognitive performance is associated with elevated levels of serum amyloid-P component (SAP) within the brain. Given SAPs role in the growth and persistence of amyloid deposits, this research project seeks to determine if SAP can influence the polymorph of amyloid-beta fibre formed, thereby influencing the level of cognitive impairment. To achieve this amyloid-beta fibres will be grown in with and without SAP, and the resulting fibres studies by solid-state magic-angle spinning to assess if the SAP has influenced the structure of the amyloid fibre formed. The data obtained will be compared with published data to assess if the structures formed can be related to particular AD phenotypes.

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

Health Law and Bioethics at the Frontiers of Innovation Postgraduate Bioethics Conference. 14 Jul 2014

The Postgraduate Bioethics Conference (PGBC) is an annual conference aimed at doctoral researchers in applied ethics broadly conceived. Over the past seven years, often with the support of the Wellcome Trust, PGBC has become established as the leading environment for doctoral candidates whose work involves bioethics to network and present their work. The theme of PGBC 2014 is Health Law and Bioethics at the Frontiers of Innovation and it will take place on 4-5 September at the University of So uthampton. There will be keynote speeches by Professor John Bryant, Professor Bobbie Farsides, Professor John Harris and Professor Jonathan Montgomery. With a focus on training and career development, we will also run two workshops. Bioethics in Practice will be led and organised by Professor Montgomery. Publishing in Bioethics , will involve a panel of editors from leading bioethics journals. Confirmed speakers are Professor Ruth Chadwick (Bioethics), Dr John Coggon (Health Care Analysis), P rofessor David Hughes (Sociology of Health and Illness) and Dr Sara Fovargue (Medical Law Review). We expect over 50 participants, of whom 24 will present a paper. The participants are likely to be mostly UK and Ireland-based doctoral researchers. Please see the website for further details: www.postgradbioethics.com.

Amount: £6,289
Funder: The Wellcome Trust
Recipient: University of Southampton

A global Chlamydia trachomatis biobank integrated with a comprehensive genome sequence database. 08 May 2013

The aim of this proposal is to establish an international biobank of C. trachomatis isolates at the University of Southampton. The primary objective will be to collect 200 diverse C. trachomatis isolates of known provenance (i.e. isolation date, geographical location and a chain of evidence for passage), which will be identified from the literature. These will be purified if necessary, then typed by sequencing of ompA/other taxonomically useful genes to confirm the identity of the isolate. Phe notypic characterisation will follow. For every isolate to be included in the collection an accompanying whole genome and plasmid sequence will be generated through our collaboration with the Wellcome Trust Sanger Institute. Once characterised, live isolates and DNA will be available for purchase by members of the research community at a nominal cost. A database will be generated containing all the information on each isolate in the biobank e.g. phenotypic characterisation, genome sequence data, recommended culture conditions; this will be made available on the biobank website. We intend that the website will be a knowledgebase for chlamydia culture to encourage newcomers to field, and to support those experiencing difficulties with the techniques needed for chlamydia culture.

Amount: £295,354
Funder: The Wellcome Trust
Recipient: University of Southampton

The role of T cell exhaustion in cutaneous squamous cell carcinoma. 20 Feb 2013

Non-melanoma skin cancer (NMSC) is the most common cancer in the UK. Immunosuppression strongly promotes NMSC (especially squamous cell carcinoma (SCC)) development and metastasis. Skin SCCs are typically surrounded by an immune infiltrate, but persistence of the cancer suggests this immune response is inadequate. Preliminary data showed that CD8+T-cells accumulate in skin SCCs in higher numbers, and have greater expression of the inhibitory receptor PD-1, than CD8+T-cells from blood, and phytoh aemagluttinin-stimulated peritumoral CD8+T-cells proliferated less than those from blood. Therefore we hypothesise that T-cell exhaustion is responsible for defective anti-tumour immunity in SCC. This project will characterise CD8+T-cells from human primary SCCs, examining for phenotypic markers of exhaustion, including PD-1, Tim-3 and BTLA, as well as assessing whether they have impaired effector functions e.g. loss of IL-2, TNF-alpha and IFN-gamma production, and reduced ability to proliferate and degranulate upon stimulation. Factors in the tumour microenvironment that promote T-cell exhaustion (including inhibitory receptor ligand expression, presence of immunosuppressive cytokines and interactions with tumour-associated macrophages) will be studied. In addition, reversibility of T-cell exhaustion will be assessed using pharmacological inhibitors (e.g. anti-PD-1, anti-Tim-3, anti-LAG-3). Ultimately this project will determine whether targeting T-cell exhaustion offers potential for development of immunopharmacologically-based treatments for SCC.

Amount: £200,443
Funder: The Wellcome Trust
Recipient: University of Southampton

Collagen assembly and accumulation in idiopathic pulmonary fibrosis. 20 Feb 2013

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with significant unmet clinical needs. No therapy has been shown to improve a median survival of only 35 months. IPF is characterised by excessive proliferation of fibroblasts and their differentiation into myofibroblasts that produce large amounts of extracellular matrix (ECM) proteins including interstitial collagens. Although altered ECM cross-linking and stiffness at the cellular-scale are proposed to play a key role in t he mediation of IPF by promoting divergent myofibroblast behaviour, it is incompletely understood if, and at what scale, collagen assembly, accumulation, and biomechanical properties are altered in IPF. I hypothesise that aberrant collagen assembly and accumulation in IPF causes altered extracellular matrix physical properties and dynamics. This may promote the disease persistence and progression. Using cross-disciplinary collaboration, I propose to compare the ex vivo assembly and biome chanical properties of collagen in healthy and fibrotic lung tissue. I will then utilise a novel in vitro 3D primary human lung fibroblast culture model, and in vivo models, to examine the kinetics of collagen production and assembly in pulmonary fibrosis. Ultimately this work will increase understanding of ECM regulation in pulmonary fibrosis, and may aid in the identification of therapeutic targets.

Amount: £219,753
Funder: The Wellcome Trust
Recipient: University of Southampton

Synthesis and characterisation of a cyclic peptide protein-protein interaction inhibitor. 01 Apr 2016

The student will synthesize analogues of a cyclic peptide protein-protein interaction inhibitor, that selectively disrupts dimerization of C-terminal binding protein (CtBP), a transcriptional co-repressor that plays a key role in tumour development. The synthesized molecule is expected to have improved potency based on a crystal structure of the peptide/protein complex.They will express the target protein and assess the binding affinity by ITC and MST. This will provide experience in a range of multidisicplinary techniques.

Amount: £2,000
Funder: The Wellcome Trust
Recipient: University of Southampton

Development of micro-computed tomography (ìCT) for enhanced diagnosis and prognosis in interstitial lung diseases (ILD) 25 Aug 2015

This project addresses long-term debilitating lung diseases, in particular Idiopathic Pulmonary Fibrosis (IPF). The project builds on pioneering work carried out by the University of Southampton and University Hospital Southampton. Nikon Metrology's microfocus CT technology (designed and built in Tring, UK) w;Jf be used to examine samples of human lung. Traditionally, very thin sections are sliced and examined under a microscope, looking for changes in the lung structure caused by disease. These sections provide only a very limited idea of how far disease has degraded the vitally important 3D structure of the lung. This pioneering work overcomes those limitations, producing a new and exciting diagnostic capability. The microfocus CT technology delivers digital scans with resolution that is hundreds of times more detailed than conventional medical CT. Results will be validated against lung samples of known diagnosis. Advanced digital analysis allows the airways, blood vessels and areas for gas-exchange to be separately identified in 3D. This technique will ultimately enable the NHS to deliver earlier and more accurate diagnosis, improving patient outcomes and accurately target medication and surgery.

Amount: £103,406
Funder: The Wellcome Trust
Recipient: University of Southampton

Open access award 2011/12. 20 Sep 2011

Not available

Amount: £30,000
Funder: The Wellcome Trust
Recipient: University of Southampton

Defining the immune response to nasopharyngeal colonisation by the commensal Neisseria lactamica 29 Jun 2016

Upper respiratory tract colonisation by the commensal Neisseria lactamica (Nlac) protects against meningococcal disease. The ability to harness this natural effect could simplify our strategy for disease prevention, however the associated mechanism is currently unknown. There is no evidence to suggest that this effect is due to bacterial competition, and the production of cross-reactive meningococcal serum bactericidal antibody does not occur. I therefore postulate that an alternative adaptive cross-reactive immune mechanism may be responsible for protection against meningococcal disease. My strategy is to firstly compare the effects that Nlac and N. meningitidis (Nmen) have on naïve T-cell priming. I will subsequently utilise a human challenge model to characterise the T-cell/B-cell memory responses induced by Nlac colonisation. If a T-cell memory response is detectable in Nlac colonised participants, I will characterise it. If not, I will identify the mechanism of immune tolerance in vitro. Finally, I will determine whether specific mucosal immunological signatures are associated with Nlac/Nmen/non-Neisseria spp. carriage. The results will improve our understanding of host-commensal interactions and inform future vaccine design, particularly in cases where commensal species are utilised as immunogen vectors, or where the elimination of mucosal carriage is paramount.

Amount: £298,900
Funder: The Wellcome Trust
Recipient: University of Southampton

Targeting human Langerhans cells to induce long-lasting tolerance in allergy. 21 Oct 2015

Langerhans cells (LCs) orchestrate cutaneous immune responses, inducing immune activation or tolerance to epicutaneously encountered antigens. Here I hypothesise that identification and targeting of the molecular switches controlling antigen presentation in human LCs will enable the induction of efficient and long lasting tolerance in allergy. Applying the systems immunology approach I developed, I aim to compare whole transcriptomes of LCs isolated from clinical samples from paediatric and adul t patients, exposed or not to an allergen, and ex vivo culture of epidermal sheets subjected to contrasting treatments. Computational analysis of molecular networks, paired with silencing of identified candidate targets, and functional validation of immunological outcomes will allow me to dissect the mechanisms of tolerance induction in human skin. I aim to address the following questions: 1) Is LC ability to induce tolerance impaired in atopic skin? 2) How is the allergen presentation re gulated in human LCs during allergen exposure? 3) How can we target the transcriptional networks in human LCs in order to induce long-lasting allergen tolerance? The outlined investigations will lead to a comprehensive understanding of allergen presentation by human LCs, and to the identification of novel therapeutic targets for induction of long-lasting tolerance in allergy.

Amount: £820,382
Funder: The Wellcome Trust
Recipient: University of Southampton

Genetic manipulation of Chlamydia trachomatis. 19 Oct 2006

The field of chlamydia research has been hampered by the inability to take a direct genetic approach to study the function and regulation of genes. The development of a system by which modified genes can be introduced will provide a significant boost to studies on this important human pathogen. Preliminary data generated in collaboration with Dr. Kahane and Prof Friedmann, presented in this application, provides 'proof of principle' that this much sought after technological goal has been reached. However, the protocol developed is time consuming, requires an experienced chlamydiologist and high level cell culture skills.Using this successful approach as a starting point we now plan to develop an efficient gene transfer system for Chlamydia trachomatis. Our key goal is to improve the protocol making it possible to establish this technology as a routine procedure for the study of chlamydial molecular biology. This will be achieved by improving the efficiency of the method, producing improved vectors for selection of transformants and using plasmid free chlamydial host strains for transformation studies.

Amount: £284,679
Funder: The Wellcome Trust
Recipient: University of Southampton

Negotiating 'Science' In 'Traditional' Indian Medicine In The Twentieth Century: The Case Of Bengali Ayurbed. 14 Jun 2006

The aim of this project is to understand the modalities of Ayurbed's engagement with 'modern' medicine in the twentieth century. By focussing principally, though not exclusively, on the pedagogical reforms instituted in the past century, not only does this project seek to bring the historiography on Ayurbed into the twentieth century, but also to deepen its analytical scope.Whereas most histories of this interaction are based in the colonial period and are concerned principally with issues of structural change towards professionalisation and commercialisation, I intend to study the epistemic changes that accompanied these structural changes. By bridging the gap between the colonial and the post-colonial contexts, I also seek to understand the varieties of ways in which the notion of 'being scientific' has been negotiated beyond the rhetorical posturing. By studying the debates and difficulties in arriving at a clear cut consensus on 'scientificity,' in the post-colonial context, its complexity may be realised in greater relief. In studying the colonial context alone there is a serious possibility of flattening out many of these complexities into antinomies of 'revival' and 'reform.' Bengal, with its four contending colleges, is an ideal site for such comparison.

Amount: £108,841
Funder: The Wellcome Trust
Recipient: University of Southampton

Functional organization, regulation and cellular roles of elongation factor (eEF) 2 kinase. 10 Nov 2008

This proposal concerns the unusual protein kinase that regulates the activity of elongation factor eEF2, i.e., eEF2 kinase (eEF2K). It builds upon recent advances in this area in the applicants laboratories. The main goals of this Programme are: 1. to establish how signalling through mTOR complex 1 (mTORC1) regulates the activity of eEF2K; in particular to identify the kinase that acts at Ser78 in eEF2K; 2. to determine how (auto)phosphorylation controls eEF2K activity and to identify add itional regulatory phosphorylation sites within eEF2K; 3. to elucidate how other regulatory inputs, such as pH, control eEF2K and their importance for the control of eEF2 and protein synthesis; 4. (i) to study the structures and functions of different domains within eEF2K and (ii) to investigate the interactions and interplay between them in the function of eEF2K and its control; 5. to explore the roles of eEF2K and the phosphorylation of eEF2 in regulating protein synthesis in response to hormones and growth factors or under conditions of cellular stress such as ATP depletion. This exploits the availability of cells, tissues and animals that lack eEF2K activity; 6. to determine whether eEF2K plays additional physiological roles and identify new substrates for this kinase.

Amount: £1,334,655
Funder: The Wellcome Trust
Recipient: University of Southampton

THe COHORTS - Consortium of health Outcome research in Transitional Socities - Brazil, Guatemala, India, Philipines, South Africa - Phase 3 06 May 2009

There is widespread interest in the early origins of adult health and capacity. However, findings supporting the notion that risks for diseases are programmed in early life come largely from high-income countries, where environmental conditions are generally good and where there is less environmental variation than is generally found in low- and middle-income countries. The five studies in COHORTS - Pelotas, Guatemala, New Delhi, Cebu, Soweto-Johannesburg are among the largest and longest runn ing prospective birth cohorts outside the rich industrialized world. A comprehensive review of the long-term consequences of maternal and child undernutrition and pooled data from the studies was published in The Lancet 2007 Nutrition Series. In 2007, the Trust funded COHORTS to undertake further analysis of early growth and feeding with the following markers for chronic diseases: systolic and diastolic blood pressure, glucose levels, and body mass index and body composition (Phase 2). The goal of the proposed research (Phase 3) is to extend the analyses already conducted to examine the role of environmental factors, particularly those related to socioeconomic status, in determining and influencing early growth patterns, later outcomes, and relationships between early growth patterns and adult health and capacity.

Amount: £108,675
Funder: The Wellcome Trust
Recipient: University of Southampton