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Results

Interventions at the end of life - social, comparative and historical analysis to promote global improvement . 16 May 2017

Care for people at the end of life has become a pressing humanitarian issue for the 21st century. Yet it is also a contested space - the focus of divided opinion, conflicting professional standpoints, fragile clinical evidence and competing models of delivery. Population ageing, changing patterns of mortality and morbidity and the growing prevalence of chronic disease present growing challenges for the development of end of life care. Recent issues concerning the Liverpool Care Pathway indicate that palliative care may prove difficult to 'roll out' across health care systems and can generate unexpected reactions. This project will develop a comprehensive analysis of the emergent field of end of life care in order to understand how interventions are developed, implemented and assessed - and with what consequences. It will take a global perspective to examine approaches of varying types and characteristics, across differing resource settings - first to build a typology of interventions and then to conduct in-depth case studies of selected examples. The project will draw on comparative, methods and interdisciplinary approaches, making use of theoretical perspectives from the social sciences and humanities to open up new lines of innovation in policy and practice. It will have a strong focus on public engagement and the use of social media - both to capture new data and to disseminate project findings. This study will transform the field - generating new theoretical proposition s and empirical knowledge that will lead to more sustainable and appropriate end of life interventions, across cultures and settings.

Amount: £138,625
Funder: The Wellcome Trust
Recipient: University of Glasgow

Representations of Stigmatised Health Issues in Scottish Fiction 1979-present 02 May 2017

The Glasgow Effect is the phenomenon of poor health and high mortality in Scotland, even after accounting for socio-economic factors. Many associated health issues, such as obesity, drug abuse and mental ill-health, are stigmatised. This is especially significant in neoliberal contexts which position health as the individual’s responsibility – or failure. These health issues are also associated particularly with Scottishness in news and popular culture, a cultural imaginary generated by, yet also independent of, sociological fact. This project will examine representations of these stigmatised health issues in Scottish fiction (1979-present). I follow critics in disability (Couser), mad (LeFrançois) and fat studies (Rothblum) who recognise the counterdiscursive possibility in illness narratives and the role of socio-political factors in representations of health. Through close reading and comparative analysis of key literary texts, I will explore illness narrative structures, identity politics, and how Scottish authors engage with or challenge dominant health discourses. Key theories include Mitchell and Snyder’s concept of narrative prosthesis, which argues ‘deviant’ bodies illuminate bodily norms; theories on illness writing and reader response by Jurecic and Hunsaker Hawkins; and Frank’s illness narrative categorisations. To understand the fiction’s context, the research will also examine extra-literary representations in newspapers in Scotland (1979-present).

Amount: £82,457
Funder: The Wellcome Trust
Recipient: University of Glasgow

Humans and animals in refugee camps 10 Nov 2016

This project explores the question what roles have animals played in refugee camps, in the past and in the present, and to what effect? Refugee camps have been a durable part of the political landscape for a century. Animals—livestock, pack animals, companion animals, or pests—have been a constant and often vital presence in the lives of people who live in them. But cross-disciplinary and comparative research on their multi-faceted role in camp life is lacking. Our goals are to establish a cross-disciplinary academic/practitioner research network; to set out and disseminate a research agenda, and identify appropriate methodologies, to explore the present and past of this subject; and to develop a collaborative funding bid to pursue that research. We will hold three cross-disciplinary academic/practitioner workshops, plus six smaller meetings with a reference group of people who have lived in refugee camps as refugees. Outputs will include a 16-page feature in the leading practitioner/policymaker publication on forced migration, a working paper for UNHCR, blog posts, and applications for follow-on funding. Stimulating new research across a range of disciplines, the project will establish effective knowledge exchange partnerships to inform humanitarian practice and improve the lives of refugees and their animals.

Amount: £47,349
Funder: The Wellcome Trust
Recipient: University of Glasgow

A sticky situation: confronting the challenges of bacterial surface adhesion 31 May 2018

Certain bacterial species can colonise to form biofilms- large structures which protect bacteria from physical and chemical removal e.g. antibiotics. If adhered to biomedical implants, bacteria can cause repeated infections which couldn't be treated by antibiotics and therefore would lead to the removal of the implant. In some patients, this would result in repeated invasive surgery. Our interest is in crystalline biofilms which can block urinary catheters and cause catheter-associated urinary-tract-infections (CAUTI). The main bacterium causing CAUTI is E. Coli in which E. Niba et al. (2008) isolated 110 genes involved in the formation of biofilms. Mutations in key genes will be created using Lambda red recombination which is a highly efficient and well established method for creating precise gene deletions. Deletions will be confirmed using PCR and sequencing. The deletion mutants will be analysed for biofilm formation using a bioflux system which generates shear force by continuous flow of liquid. This is an open system ensuring nutrients are available and thereby favouring biofilm formation. Both pathotypes and their respective mutants will be tested for the capacity to form biofilms at a range of temperatures. Data from the above experiments will be quantified using ImageJ software.

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

Brain Rhythms in Altered Vision After Stroke (BRAVAS) 08 Nov 2017

Stroke affects 152,000 people in the UK each year, and up to 80% experience visual impairment as a result. Post-stroke disorders such as hemispatial neglect (a loss of visual attention to one side of space) are notoriously difficult to treat, and are associated with limited functional recovery and reduced quality of life. In healthy adults, visual processing is modulated by neural oscillations which help to promote or suppress incoming visual information. Specific oscillatory frequencies are known to be disrupted in stroke, yet at present it is unknown how these oscillations are related to hemispatial neglect. I aim to develop a new intervention for neglect via 3 interlinked and interdisciplinary clinical projects: 1) to identify, using electroencephalography (EEG), the oscillatory markers of a temporary, induced improvement in neglect during a phasic alerting protocol, 2) to identify longer-term oscillatory markers of improvement from neglect using magnetoencephalography (MEG) at 1-3 months vs 6-12 months post-stroke, and 3) to compare two targeted interventions to modulate pathological oscillatory activity, using a biofeedback protocol vs non-invasive brain stimulation. This translational programme will bring together knowledge and expertise from cognitive neuroscience and clinical stroke rehabilitation to develop a novel intervention to treat visual impairment after stroke.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Glasgow

The skin as a reservoir for trypanosomes: the key to understanding transmission and disease pathology 28 Nov 2017

Human African trypanosomiasis is a fatal disease caused by trypanosome parasites, transmitted between mammalian hosts by the bite of a tsetse fly. We recently discovered that trypanosomes sequester to mammalian skin during infection, forming an undiagnosed, untreated, reservoir of disease. I hypothesise that this reservoir presents a substantial barrier to current control programmes and that the detection and elimination of skin-dwelling parasites will be crucial for the elimination of trypanosomiasis. I also hypothesise that the molecular pathways involved in extravasation to the skin are shared with those allowing extravasation into other organs, leading to the main pathological consequences of infection (an evolutionary by product of the drive for transmission). I aim to test these hypotheses using a combination of field and laboratory work. The fieldwork is aimed at determining the extent and role of skin-dwelling trypanosomes in humans and livestock (reservoir hosts) and developing a Raman spectroscopy-based non-invasive diagnostic. The laboratory-based work will use transcriptomics and genetic analysis to identify the key genes involved in extravasation. Together these approaches will allow a greater understanding of extravasation that will be key for the development of new diagnostics, transmission and pathology blocking agents as well as identifying novel areas of host/parasite interaction.

Amount: £2,537,726
Funder: The Wellcome Trust
Recipient: University of Glasgow

Tuft Cell Activation and Intestinal Immunity 17 Jul 2018

Immunity to nematode parasites requires sequential activation of innate and adaptive immunity in a concerted Type 2 response dependent on the cytokines IL-4, IL-13 and IL-25. Our work, and that of others, has identified a novel epithelial cell type that is critical to initiation of this response, known as tuft (or brush) cells. Most significantly, tuft cells are a major source of IL-25 during gastro-intestinal nematode infection, which induces IL-13 production from innate lymphoid cell type 2 (ILC2s), to activate further innate and adaptive cell populations. They also express high levels of the enzymes that produce acetylcholine and lipid mediators implicated in immunity. Tuft cells are found in other mucosal locations, including the lungs, and are highly conserved across the Mammalia, including in ruminants where intestinal nematodes are a major problem. A fascinating aspect is their expression of taste receptors suggesting that they may chemically ‘sense’ the presence of nematodes. In this proposal we seek to (i) determine the immune effector functions of tuft cell mediators; (ii) identify molecules from parasites that may activate tuft cells; and (iii) establish whether tuft cell functions are conserved in ruminants and may lead to new strategies for control of nematode infection in sheep.

Amount: £1,203,739
Funder: The Wellcome Trust
Recipient: University of Glasgow

The Physician of the Soul: Medicine and Practical Ethics in Galen 17 Jul 2017

This project aims to shed light on Galen’s role as a moralist and soul-doctor, an aspect of his intellectual profile that has been little studied and poorly understood. To that end, it proposes to examine for the first time in a holistic manner his psychological and ethical works alongside a large number of technical tracts – both medical and philosophical – that have moral and/or moralising elements and connotations. The ultimate goal will be to give prominence to the dynamic interdependence between medicine and practical ethics in its historical, social, and cultural context. Key questions are: How does Galen adjust his moral agenda to the needs and requirements of contemporary elite life? How does he communicate his ethical teachings and whom is he addressing? What techniques does he employ in assigning himself moral authority and how successful are they on different occasions? The project will place Galen firmly in the tradition of philosophical writing on the therapy of emotions, therefore also helping us to properly reassess his influence on later Arab moralists-cum-physicians. On another level, the project will be the starting point for more in-depth research on the reception of Galenic (and not just Hippocratic) medical ethics in modern medicine.

Amount: £248,257
Funder: The Wellcome Trust
Recipient: University of Glasgow

Study of effects of surface bound, low-dose PDGF on cell motility – towards improved wound healing 27 Apr 2017

In vivo, GFs are secreted by cells and tether to the extracellular matrix (ECM), e.g. the heparin-binding domain of fibronectin. This ECM interaction allows cells to exploit low-dose GF signals in topical locations. In clinic, GFs are supplied in soluble format in supraphysiological dose to maintain concentration at the injury site, accepting that much of the GF will distribute around the body; this causes unwanted off-target side effects that can be serious (e.g. death). Materials are being designed to deliver GFs to specific targets and to control the release of the GFs, but still released at high dose and in unbound format allowing systemic distribution. The ideal is to use materials to mimic the human ECM. However, proteins such as FN bind to materials in globular conformation so that GFs do not efficiently bind/cannot be exploited by cells. We have discovered a polymer, polyethylacrylate (PEA) that causes spontaneous opening of FN in fibrilar conformation and this allows biomimetic GF tethering. In the project we will bind PDGF and study cell motility, key in wound healing, as cell recruitment will determine wound closure.

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

Nursing, Reproduction, and Writing: Naomi Mitchison’s Science Fiction as Activism 29 Feb 2016

This study will explore the ways in which the experiences of the Scottish writer Naomi Mitchison (1897-1999) as both a geneticist and a nurse shaped her science fiction, her political writing, and her activism in favour of women’s reproductive rights. Through archival research and literary analysis, informed by science fiction studies, this project will explore Mitchison’s importance to twentieth-century medical humanities. The outcomes of the project will be a conference presentation and a peer-reviewed journal article, with potential for future projects.

Amount: £1,534
Funder: The Wellcome Trust
Recipient: University of Glasgow

Mitochondrial tRNA import in T. gondii 01 Apr 2016

The protozoan phylum Apicomplexa encompasses approximately 5000 species of obligate intracellular parasites, including those responsible for malaria and toxoplasmosis. Unlike humans, the Apicomplexans posess a large single mitochondrion which fully relies on mitochondrial tRNA import (MITI) from the cytosol for translation to proceed. The Sheiner lab aims to euclidate Acomplexia-specific adaptations which allow for the import of all tRNA from the cytosol to the mitochondrion and to develop new methods for MITI study which may be employed in wider mitochondrial investigation. By identifying acomplexan apecific adaptations via analysis of the Toxoplasma MITI translocon, the Sheiner lab hopes to contribute another solved MITI system to the expanding list and to increase our understanding of mitochondrial evolution across the eukaryotic tree. The main goal of this project is to examine the role of a group of potential components of the import machinery in mitochondrial tRNA import in T. gondii by characterizing the subcellular localization and function of bioinformatically identified T. gondii MITI components. By understanding the molecular detail of this parasite specific mechanism we may identify and characterize new potential target for intervention, thus contributing to the process of drug development.

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

Natural Killer cells and oncolytic adenovirus therapy in ovarian cancer. 21 Nov 2013

Epithelial ovarian cancer is an immunogenic disease. Oncolytic viruses (OVs) are a new class of anti-cancer agent that generates potent innate and adaptive immune responses, which may influence clinical efficacy. NK cells are CD3- immune cells that play key roles in combating viral infection with the ability to lyse malignant cell and modulate adaptive immune responses. Further development of OVs will require understanding of their interactions with the host immune system. This research ai ms to assess the specific role of NK cells in the activity of oncolytic adenovirus in ovarian cancer. Hypothesis: NK cells within the peritoneal cavity attenuate the efficacy of OVs in ovarian cancer. Key goals: 1. To investigate the pattern of NK cell ligand and cytokine expression in human and murine ovarian cancer cells and these change following OV infection by flow cytometry, immunoblot, qRT-PCR and Luminex multiplex immunoassays. 2. To investigate NK cell composition in ovarian ca ncer ascites by flow cytometry and cytokine production by Luminex. 3. To investigate how NK cells influence the efficacy of oncolytic adenovirus through co-culture (NK cell lines and primary ascites cells with autologous NK cells) and in vivo xenograft experiments.

Amount: £206,925
Funder: The Wellcome Trust
Recipient: University of Glasgow

Institutional Strategic Support Fund 07 Sep 2016

Not available

Amount: £2,250,000
Funder: The Wellcome Trust
Recipient: University of Glasgow

Treatment effectiveness in multimorbidity: Combining efficacy estimates from clinical trials with the natural history obtained from large routine healthcare databases to determine net overall treatment benefits. 18 May 2016

This research will develop and validate a novel method for estimating net overall treatment benefits (effectiveness) for patients with multimorbidity, using Bayesian Evidence Synthesis (BES). Clinical guideline development routinely uses evidence synthesis, which combines estimates of relative treatment efficacy (RTE) from clinical trials with standard treatment comparator (natural history) event rates from observational data to estimate effectiveness in target populations. Bayesian approaches to evidence synthesis can accommodate more complex modelling, but methods to address the increased complexities of multimorbidity have not been developed. This research will address the clinical and methodological barriers to this use of BES. Key Research Goals: 1. Summarise parametrically the variation in RTE according the presence and severity of comorbid diseases for a range of drug-groupings, outcome-types and comorbidities 2. For an exemplar indication, combine these summaries (1) with published trial results of specific treatment comparisons to produce comorbidity-specific estimates of RTE, and validate this approach empirically 3. For the same exemplar, show how these comorbidity-specific efficacy estimates (2) can be combined with administrative-data derived natural history rates, via BES, in order to produce comorbidity-specific estimates of effectiveness 4. To encourage the adoption of this novel method via software tools and documentation

Amount: £709,217
Funder: The Wellcome Trust
Recipient: University of Glasgow

Analysis of a fragment of the endotoxin binding site of Factor C 01 Apr 2016

Horseshoe Crab blood has a unique ability to detect bacterial agents. This phenomenon has long been exploited by the pharmaceutical industry to create assays that ensure sterility of drugs or medical equipment. Although much is known about the signalling cascade eliciting the response following the exposure to LPS endotoxin, the specific molecular events underlying this process are still unknown. Factor C has been identified as the protein triggering the cascade of events leading to bacterial inactivation. The protein exists as a zymogen. The binding of endotoxin results in a conformational change that activates its serine protease causing autolysis. This triggers the cascade that causes blood coagulation and bacterial neutralisation. The high affinity of Factor C for the endotoxin is important when considering developing a highly sensitive detection system. As part of the Smith lab’s work to fully characterise the molecular mechanism of the conformational switch in Factor C, the aim of the project is to map the endotoxin binding site on the LPS-binding CCP1 domain from L. polyphemus Factor C, providing an answer to the question: How does lpFC recognise endotoxin?

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

Institutional Strategic Support Fund Phase2 FY2014/16 27 Oct 2014

The Wellcome Trust Institutional Strategic Support Fund (ISSF) helps to support research at the University of Glasgow related to the Trust’s research goals, particularly through the Glasgow Polyomics initiative. This award delivers benefits and impact in multiple areas by: Enabling quality research by providing access to specialist services in high-throughput omics data generation, and key resources such as data analysis software. Developing researchers across multiple disciplines through fellowships and other funding awards. Promoting science and technology through outreach in schools, community events, and public exhibitions. Achieving knowledge transfer across the scientific community via training courses, seminars and symposia

Amount: £1,500,000
Funder: The Wellcome Trust
Recipient: University of Glasgow

The Medical History of the Refugee Camp 10 May 2016

Last year, the number of refugees in our world passed the 20 million threshold for the first time since 1992 (UNHCR, 2015). The UN refugee agency may have adopted a policy of seeking alternatives to camps, but refugee camps have been the dominant model of managing refugee crises for a century. My proposed research offers a historiographical analysis of the medicalization of refugee camps. The research will investigate how refugee camps have developed as sites of professionalised medical interventions. It will analyse how camps have developed as sites of medical risk for those inhabiting them. It will investigate if refugee camps have become sites for managing risks to others; have camps developed as sites of disease control, for the benefit of host communities and the global community? The research will draw from archival documents to investigate the strategy and role of international bodies (NGOs and the UNHCR) in the medicalisation of refugee camps. The research goals are (i) to complete a challenging contribution to the body of knowledge (ii) to strengthen a multi-disciplinary field of study in medicine and the humanities (iii) to open-up avenues for new research also of value to policy-makers and strategic decision-makers in contemporary scenarios.

Amount: £83,593
Funder: The Wellcome Trust
Recipient: University of Glasgow

Elucidating the mechanisms by which mosquito-borne viruses disseminate in vivo and cause disease. 28 Apr 2015

This project will determine the cellular basis by which arthropod-borne viruses (arboviruses) disseminate in vivo; a process that is essential for their onwards transmission and to pathogenesis. This will provide novel, fundamental insights that will aid the design of innovative treatment strategies. Arboviruses are a large group of emerging, medically important pathogens for both humans and economically important livestock. Following infection by an arthropod-bite, arboviruses disseminate to t he blood (viraemia). Subsequently, arboviruses spread to distal sites where they can cause severe disease including encephalitis, arthritis or hemorrhagic fevers, the severity of which depends on the establishment of high viraemia. Importantly, little is known about which cell types fuel this viraemia and how arboviruses spread to distal sites. This project will determine the origin of viraemia using an innovative technique based on cell type specific inhibition of virus replication. By genetic ally engineering viruses to encode a microRNA target site in their genome, viral replication will be blocked specifically in cells expressing the corresponding microRNA. This will enable us to dissect in unprecedented detail the contribution of viral replication in defined cell compartments from the inoculation site to distal tissue, and so define the critical events that lead to systemic spread.

Amount: £96,848
Funder: The Wellcome Trust
Recipient: University of Glasgow

Regulation of stem cell function during tissue homeostasis and transformation. 29 Oct 2014

Stem cells maintain tissue homeostasis by adjusting their function to microenvironmental or niche signals. Deregulation of such signals results in either tissue loss or uncontrolled stem cell proliferation, the latter often associated with cancer. The intestinal epithelium is a paradigm for the study of stem cell biology. The Drosophila adult midgut has remarkable resemblances to the mouse small intestine, including the presence of dedicated stem cells. During my post-doctoral work I developed Drosophila models of intestinal hyperplasia and regeneration, which have uncovered novel mechanisms regulating stem cell proliferation and suggests that the fly midgut could be a useful paradigm to understand the biology of multiple adult self-renewing epithelia. The overall goal of my research is to combine Drosophila genetics with mammalian models systems to understand how cell autonomous and niche-derived signals regulate adult stem cell proliferation in response to damage as well as in tumo urigenesis. In this proposal I aim to: 1-Identify and characterize novel mediators of tissue hyperplasia and damage-induced regeneration in the adult Drosophila midgut. 2-Translate results from Drosophila into mammalian model systems. 3-Characterize the role of G-protein coupled receptor dLGR2/LGR4 as tumour suppressor.

Amount: £985,310
Funder: The Wellcome Trust
Recipient: University of Glasgow