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Volunteering Matters
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Results

Grant to Volunteering Matters 23 Mar 2015

The men go forth to Battle, the women wait and knit

Amount: £9,800
Funder: The National Lottery Heritage Fund
Recipient: Volunteering Matters
Region: North East
District: County Durham

Grant awarded to Community Service Volunteers (Training and Enterprise NE) (Tyne & Wear) 10 Mar 2009

To provide support and mentoring to people with mental health problems to help them volunteer in Newcastle.

Grant awarded to Community Service Volunteers (Training and Enterprise NE) (Tyne & Wear) 13 Jul 2004

To provide daycare services to older people living in high rise flats in Newcastle.

Positive Futures London 18 Nov 2015

This project, based on a established youth-led volunteering model is expanding as a result of self-referrals and is being delivered in Hackney, Haringey and Tower Hamlets. It will support young people aged 13 to 25 to deliver volunteering and social action projects which they have identified to be of benefit to the local community. The aim of project is that all of the young people who are participating in it will develop key skills and have positive experiences that will shape their personal development.

Amount: £387,576
Funder: The Big Lottery Fund
Recipient: Volunteering Matters
Region: London
District: Hackney London Boro

The role of interferon response genes in an experimental model of Alzheimer's Disease 31 May 2018

Emerging evidence suggest that systemic infection can accelerate the onset and/or progression of cognitive decline in Alzheimer’s disease, but the underlying biological mechanism remain unknown. Exposure of AD mouse models to a real systemic infection results in exaggerated neuroinflammation and AD-like pathology and preliminary microarray analysis suggest this may be due to increased levels of type I or II interferon and/or it’s down-stream signalling pathways. Interferons are produced in response to viral and bacterial infections and well known to be associated with mood changes and depression. In this project we will test if these pro-inflammatory cytokines also play a role in progressing AD-like pathology. Brain tissue from AD mice exposed to a systemic bacterial infection has already been collected, with a control group treated with saline. The expression levels of interferons and their signalling pathways will be explored in this archived tissue and in primary neuronal cultures expressing human Tau. The in vitro cultures will allow us to test if exposure to interferon promotes spreading of tau pathology and if inhibition of the signalling pathways prevents progression of AD-like pathology. This could later be applied to in vivo AD disease models, taking into consideration behavioural changes.

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

Uncovering the Molecular Mechanisms of Asymmetric Cell Divisions in Mammalian Adult Epithelia 04 Dec 2017

Loss of asymmetric cell divisions (ACDs) regulation in the normal self-renewing stem cells is entwined with the growth and progression of poorly differentiated cancers. Yet, the molecular mechanisms controlling the execution of symmetric versus asymmetric divisions in adult epithelia are still unfolding. We recently demonstrated that KIF5/kinesin-1 is essential for mammary epithelial cell divisions and cytoarchitecture by governing the trafficking of the spindle orientation and apical polarity components, respectively. Whether KIF5/kinesin-1 couples spindle orientation and polarity machineries during mitosis to promote ACDs; and whether other mechanisms are involved remain open questions. Here, we will address these questions in mammary 3D organoids. We will use CRISPR/Cas9 gene editing to generate cells expressing AID-tagged endogenous KIF5/kinesin-1 to allow inducible and rapid degradation of the microtubule motor specifically during mitosis, for a precise evaluation of the role it plays in ACDs. We generated cells expressing GFP-tagged LGN –a key player in the spindle orientation machinery–to purify and analyse the LGN-containing complex by LC-MS/MS mass spectrometry and identify novel factors that participate to ACDs. These studies will elucidate the molecular mechanisms of ACDs in the mammary epithelia and provide rational for subsequent detailed investigations in vivo of their precise roles in development and homeostasis.

Amount: £100,000
Funder: The Wellcome Trust
Recipient: University of Southampton

Investigating the mechanisms of Parkin-mediated mitophagy 29 Nov 2016

Determining how cells maintain homeostasis under times of stress is vital to understanding a wide-range of disorders, from neurodegenerative diseases to cardiomyopathies. Autophagy is a catabolic cytosolic pathway that functions to degrade damaged organelles and mis-folded proteins, while providing a protective mechanism under stress. Mitophagy, the selective autophagic pathway for mitochondria limits oxidative stress by degrading damaged mitochondria through a mechanism involving ubiquitylation and recruitment of autophagic machinery. One mechanism of mitophagy, which is dysregulated during Parkinson’s disease, is the PINK1-parkin pathway. In this proposal, we will identify and characterise regulators of parkin which facilitate its recruitment to mitochondria. We will focus on an adaptor protein complex Tollip-Tom1, which has been suggested to be linked to this process, and which functions to regulate trafficking along both the endolysosomal and autophagic pathways. We will utilise microscopic imaging and biochemical assays to dissect the spatiotemporal regulation of parkin-mediated mitophagy following targeted loss of function of Tom1 and Tollip. In addition, we will utilise CRISPR-Cas9 technology, coupled to cDNA reconstitution experiments, and primary patient-derived fibroblasts to understand mechanisms of parkin recruitment following mitochondrial damage. The outcomes will provide crucial mechanisms of how cells regulate PINK1-parkin mediated mitophagy in order to maintain their health.

Amount: £99,277
Funder: The Wellcome Trust
Recipient: University of Southampton

Use of a Drosophila model to study circadian control of metabolic health. 27 Apr 2017

Internal daily timekeeping systems known as circadian clocks are used by all types of organisms to regulate their metabolism. For example, the clock-controlled scheduling of food intake and use affects health and longevity in both mammals and insects. Time-restricted or nutrient-restricted feeding improves the health of both mice and fruit flies (Panda, Science 2016). The period gene, which plays a key role in the circadian clocks of animals, provides a link between daily timekeeping and metabolic health. Flies lacking the period gene store less glycogen and triglycerides in spite of ingesting more food and are, therefore, more sensitive to starvation. I propose to test where and how the period gene provides this metabolic function. In particular, I will ask whether its role in starvation resistance is due to its control of sleep/wake rhythms or its function in periperhal clocks of metabolic tissues such as the fat body. Moreover, Dr Wijnen's laboratory recently showed that the period gene is induced at colder temperatures (Goda et al., Proc Biosci 2014) and I will test whether period-mediated starvation resistance is found preferentially at colder temperatures.

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

Open Access Block Awards 2016/17 30 Sep 2016

Not available

Amount: £4,817
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

What are the molecular mechanisms regulating neuronal sensitivity to BDNF? 31 May 2018

Neurotrophins and their receptors play a key role in the maintenance and remodelling of the nervous system, and defects in trophic signalling are associated with mental illness as well as neurodegeneration. To date, the cellular mechanisms regulating neurotrophin receptor bioavailability are not fully understood. Here we focus on BDNF and its receptor, TrkB, which are widely expressed throughout the central nervous system. This project will investigate the role of two novel potential TrkB regulators that recently emerged from our screens. Candidates will be expressed in HEK-TrkB cells and primary cortical mouse neurons, and (i) TrkB receptor expression levels and (ii) downstream signalling events will be investigated using both Western blotting and immunofluorescence techniques. These experiments will address whether the candidates modulate TrkB availability and activity. A better understanding of the cellular mechanisms underlying TrkB regulation may highlight potential therapeutic targets to counteract TrkB degradation and restore sensitivity of vulnerable cells to the beneficial actions of BDNF.

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

Novel strategy to tackle multidrug-resistant Staphylococcus aureus. 28 Apr 2015

Our preliminary data suggested mannitol-1-phosphate-5-dehydrogenase, a key enzyme in the mannitol pathway in Streptococcus aureus, as a promising therapeutic target, which is not subject to the antibiotic-resistant mechanism of the bacterium. To develop this hypothesis into a major project, we propose a research project aimed at validating our concept also in multidrug-resistant Streptococcus aureus, and characterising mannitol-1-phosphate dehydrogenase biochemically and structurally. To fulfil this aim, we will achieve following specific objectives: 1. Validation of the mannitol-1-phosphate-5-dehydrogenase as a novel target in multidrug-resistant Streptococcus aureus; 2. Kinetic characterisation of mannitol-1-phosphate-5-dehydrogenase; 3. Determination of the X-ray crystal structure of the free enzyme and complex with substrates or inhibitors to provide a framework for the inhibitor development; 4. Preliminary screening of commercial and open access inhibitor libraries as a basis for further inhibitor development. At the end of the project, we will have sufficient data and strong rationale that will place us in positon to stage a main project directed at developing a general strategy that exploits the inhibition of mannitol-1-phosphate-5-dehydrogenase for treating multidrug-resistant pathogens.

Amount: £99,613
Funder: The Wellcome Trust
Recipient: University of Southampton

Biomedical Vacation Scholarship. 22 Jun 2015

Not available

Amount: £11,750
Funder: The Wellcome Trust
Recipient: University of Southampton

Mobile-ising for Sexual Health: Digital technologies and Sexual Health Advocacy 29 Feb 2016

This study builds on previous work done by Boyce (2011,2014) and Dasgupta (2012,2014) on the challenges facing HIV prevention and other sexual health advocacy with MSM's (Men having sex with men) in eastern India. This study will explore emerging digital platforms in India and examine the challenges and opportunities of using mobile and digital platforms for sexual health advocacy amongst gay, MSM and trans* communities (all highly stigmatised groups) in India. The primary goals of this project are: Identify NGO services in Eastern India that provide sexual health advocacy Identify and report on uses of social media and mobile platforms by MSM's in Eastern India Report on the experiences of NGO's using digital media platforms in developing advocacy and support campaigns Conduct discussions with stakeholders on how to leverage and use digital media for HIV prevention and sexual health advocacy Feed the information back to national bodies and Public Health officials through a report The outputs of this project will include a comprehensive report and a journal article. Building on these results a larger project will be developed. The research will be undertaken between the School of Global Studies, University of Sussex and Media Transformations Group at University of Southampton.

Amount: £3,740
Funder: The Wellcome Trust
Recipient: University of Southampton

Lifecourse trajectory of muscle strength and the relationship with physical activity: exploiting the HALCyon and FALCon Cohort Consortia. 21 Jun 2012

Muscle strength is central to the current and future health of older people. There is increasing recognition that muscle strength in later life depends not only on the rate of decline but the peak reached earlier in life, but the trajectory of muscle strength across the lifecourse and its determinants have been little studied. As no one cohort has repeated measures of strength for the same individuals from childhood to old age, it is necessary to combine repeated measures from several cohorts in order to construct a lifecourse trajectory of muscle strength. Customary physical activity appears to be an important modifiable factor related to muscle strength but the optimal time in life for beneficial intervention is unclear. Understanding when increased customary physical activity could have maximal effect would have major relevance for potential public health interventions to improve health in old age. Aims 1. To describe a lifecourse grip strength trajectory from childhood to old a ge, by combining data from several UK cohorts 2. To compare the influence of physical activity on grip strength at different ages across the lifecourse 3. To explore the relationship between physical activity and subsequent grip strength trajectory

Amount: £176,331
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

Value in People award. 18 Jul 2007

Not available

Amount: £150,000
Funder: The Wellcome Trust
Recipient: University of Southampton

Developmental programming of adiposity and insulin resistance in rural and urban Indian children, and pilot work to explore its reversibility during adolescent growth. 16 May 2006

This project comprises further work in two large well-characterised birth cohorts of Indian children, in Pune and Mysore, whose mothers were recruited prospectively and had detailed nutritional assessments (Pune) and/or biochemical measurements (Pune and Mysore) during pregnancy. The babies had detailed anthropometry at birth and post-natally. The project will investigateassociations of 1) maternal data and 2) newborn anthropometry with cardiovascular disease risk markers in the children at the age of 11-12 years (Pune) and 9-10 years (Mysore). Risk markers will include body composition (DXA and bio-impedance), blood pressure, insulin resistance (HOMA) and serum lipids. Earlier studies in these children at 5-6 years showed that those whosemothers had lower vitamin B12 status and higher folate status (Pune) and children of mothers with gestational diabetes (Mysore) were more adipose and hyperinsulinaemic. The project will also include pilot work in sub-samples of the children, in preparation for intervention studies in the full cohorts to determine the reversibility of adiposity and insulin resistance. Interventions

Amount: £391,289
Funder: The Wellcome Trust
Recipient: University of Southampton

The role of sarcolipin in thermogenesis. 15 Oct 2008

We have shown that, in vitro, sarcolipin, a small transmembrane peptide found in skeletal muscles of larger mammals (e.g. rabbits humans) but absent from the muscles of smaller animals such as mice, uncouples calcium transport by skeletal-muscle sarcoplasmic-reticulum calcium pumps, leading to a significant increase in thermogenesis. Thermogenesis plays a major role in maintaining body temperature as well as moderating the effects of excess dietary calories thereby reducing obesity. The contri bution to overall thermogenesis played by sarcolipin in vivo has not been assessed and is the subject of this proposal. We will produce a transgenic mouse, in which sarcolipin is over-expressed. These transgenic animals will be characterized in terms of their body weight, energy expenditure and responses to different dietary regimes and ambient temperatures to measure the outcomes of the thermogenic effects of sarcolipin in a whole animal. Sarcolipin and calcium pump levels will be measured in h uman skeletal muscle to estimate the level of thermogenesis resulting from the presence of sarcolipin in human skeletal muscle. In addition, we will examine the mechanism by which sarcolipin causes the uncoupling calcium transport, using mutagenesis to alter key residues thought to interact with the calcium pump.

Amount: £229,627
Funder: The Wellcome Trust
Recipient: University of Southampton

Replication of Noroviruses: determinants of tropism. 02 Oct 2008

Human noroviruses are amongst the few remaining non-cultivable human viruses. Numerous attempts in many laboratories over the past two decades have failed to establish a routine cell culture system for the propagation of these viruses. The aims of this programme are to determine the molecular basis of tissue tropism and elucidate the interactions between viral and host cell proteins. Initially we will use the cultivable murine norovirus to investigate the role of the unique caliciviral N-term protein and we also wish to focus on the viral 3C-like protease and its role in the replication process through interactions with viral proteins, host proteins and the viral RNA genome itself. We will use our recently published reverse genetic system for the recovery of modified noroviruses from cloned cDNA. To understand the specific requirement for the replication of human noroviruses we propose to construct chimaeric viruses by replacement of sections of MNV proteins with the human equival ent. Therefore, the major aims of the programme are: 1). To determine key intracellular factors that determine norovirus tropism. 2). To investigate the intracellular role of the N-term protein 3). To investigate the role of the 3C-like protease in norovirus replication.

Amount: £473,899
Funder: The Wellcome Trust
Recipient: University of Southampton