- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 25 Jan 2019
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Lipoxygenase (LOX) enzymes are expressed by infiltrating immune cells and are involved in innate immune and inflammatory response, all of which are fundamental processes in wound healing. The overarching aims of this larger body of work is to evaluate the role of 12/15-LOX in the cellular orchestration of wound healing using a murine model. We have induced full thickness (4mm) wounds in wildtype and 12/15-LOX knockout mice, then measured wound closure rates and harvested skin tissue at various time points post wounding and conducted histological evaluation of skin sections. Our initial data has found that in 12/15-LOX knockout skin there is enhanced fibroblast expansion, and a reduced infiltration of macrophages, both of which might be beneficial in chronic wound states where failure in fibroblast proliferation and an overt inflammatory state occur. However chronic wounds also displays deficits in wound re-epithelialisation and given that 12/15-LOX products can inhibit epidermal hyperplasia (by modulating cyclin/CDK signalling), we believe that KO mice might also display an enhanced re-epithelialisation phenotype. Therefore, to test this hypothesis we will explore the rate of re-epithelialisation and the cytokeratin profile of epithelial keratinocytes in KO and wildtype mice at various time points post wounding.
Communication between immune and stromal cells is key to immunological memory within pathogen infected tissues 10 Apr 2018
Pathogens trigger an accumulation of immune cells in the infected tissue. Incoming immune cells adapt to their new environment, communicating with infected stromal cells to ensure pathogen control. Tissues do not immediately return to homeostasis following pathogen clearance. Some pathogen-specific T cells remain, differentiating into Tissue Resident Memory cells (Trm). The tissues’ stromal cells also retain an imprint of the infection with prolonged expression of immune-related genes. Currently, we have only limited understanding of the cells and molecules involved in establishing and maintaining these infection-induced changes and how immune and stromal cell communication impacts on protective immunity. These are key question for vaccines that aim to induce immune protection within tissues to provide rapid protective immunity. This proposal is based on our findings that antigen-presentation and inflammatory cytokine production drives prolonged changes in lung CD4 Trm cells and epithelial cells and fibroblasts. Our key goals are to define the mechanistic basis for these changes by identifying the cells and molecules that influence the generation, maintenance and protective responses of infection-altered immune and lung stromal cells. This research will provide a conceptual breakthrough in our understanding of how cell commination influences protective memory and novel insights relevant to improved vaccine design.
In today’s world, it is most desirable to optimize cognitive capacities, such as learning, across the lifespan. One fundamental, yet poorly understood, method is via a person’s intrinsic curiosity. Despite the ubiquity and importance of curiosity in everyday life, we have a very limited appreciation of the exact neural mechanisms of curiosity-enhanced learning. Because initial curiosity studies have relied on the passive encoding of material, one fundamental aspect of curiosity – active exploration to acquire further knowledge – remains to be investigated. I, therefore, propose a new virtual reality paradigm to characterize the neural mechanisms of how active curiosity enhances memory. Across three principal approaches, I will ask how separate stages of memory (orientation vs. initial learning vs. different modes of consolidation) contribute to curiosity-related memory enhancements and why curiosity-based learning might vary between healthy individuals. I will uncover whole-brain mechanisms and ‘zoom in’ on specific curiosity- and memory-related brain structures using complementary state-of-the-art measures and analyses. Combining such approaches is vital if we are to understand how curiosity enhances memory, but may also aid crucial translation of laboratory-based findings on learning and memory to real-world issues (e.g., influence on educational policies and implications for cognitive resilience in the elderly).
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), affecting 2.5 million individuals worldwide. Treatments are available, but are complicated by side effects and variable response profiles. There is an urgent need to define the pathogenesis of MS and design novel therapeutics. There is evidence that CD8 T-cells play a major role in the pathogenesis of MS. Studies also suggest a role for herpes viruses in MS, however, it remains unclear what triggers di sease. My preliminary data demonstrates that CSF resident T-cells have an antigen-driven phenotype. T-cell receptor (TCR) usage in the CSF resident CD8 T-cell repertoire is highly skewed with a restricted number of dominant TCRs. I hypothesize that a viral infection, such as EBV, triggers CD8 T-cells, which subsequently target and damage host cells. Here, I intend to identify the pathogenic triggers of dominant CSF-resident T-cells, thereby elucidating the aetiology of this debilitating disease. Specific aims: 1. To perform an in-depth phenotypic analysis of T-cell populations in the CSF of MS patients. 2. To identify dominant CSF resident TCRs in MS patients. 3. To define the pathogenic triggers of dominant CSF-resident TCRs.
'Dissecting the Page' is the first conference on medical paratexts, to be held on 11 September 2015, University of Glasgow. Understanding paratext as the apparatus of graphic communication (titles, prefaces, illustrations, marginalia, etc.), the conference will combine periodic and disciplinary approaches to the paratextual study of medicine, from medieval medical manuscripts to contemporary graphic novels. It will draw together academics, archivists, and creative and medical practitioners inter ested in graphic representations of medicine. By focusing on medical paratexts across multiple periods, we hope to establish a multidisciplinary network of scholars, combining material, textual, and graphic approaches to medical history and practice. We have three keynote speakers: Professor Graham Caie, Professorial Research Fellow, University of Glasgow; Dr Deborah Thorpe, postdoctoral scholar, University of York; Dr Ian Williams, physician, artist and writer. All three speakers have expres sed interest in our conference. Prof. Caie will draw on his extensive knowledge of the Hunterian Collection. Dr Thorpe will speak on neurodegenerative disorders and medieval scribes. Finally, Dr Williams will discuss the creative and medical practices that influence his art, drawing on 'Graphic Medicine' and 'The Bad Doctor'. We will host fifty delegates, and intend to publish an edited collection from the conference proceedings.
Landscapes of Health: The Black Sea in the Socialist World is a workshop with two main objectives. First, it seeks to develop our understanding of the role of Black Sea health resorts in socialist medical theory, practice, and culture. It highlights the importance of the sea, rest, environmental health, and natural healing to socialist ideas and practices of health. The workshop develops the idea of the Black Sea coastline of socialist Bulgaria, Romania and the Soviet Union as a shared zone of h ealth in the geography of the socialist world. Second, the workshop develops the idea of health resorts as international meeting places. The workshop marks the 70th anniversary of the Yalta conference (February 4-11, 1945), and brings to light the role of medicine and socialist ideas of health in Cold War diplomacy. Health resorts were showcases of the socialist world, in a Cold War contest fought publicly over welfare and standards of living. This workshop brings together for the first time scholars studying the health resorts of the Black Sea, with contributions from specialists in the history of medicine, history, film, architecture and urban planning, and scholars of both the Soviet Union and the Eastern Bloc.
Infections of animals or humans by viruses can result in many different clinical outcomes. Studying natural models of infection and disease can help us gain a full understanding of the mechanisms of viral pathogenesis, in the knowledge that this is influenced by virus-host co-evolution. In this proposal, we will study bluetongue, a vector-borne disease caused by bluetongue virus (BTV). Bluetongue is one of the major viral diseases of livestock. Essentially all domestic and wild ruminant are susceptible to BTV infection but the resulting clinical symptoms vary considerably (from mild fever to lethal haemorrhagic fever). In this proposal, we will address how a pathogenic virus renders some infected hosts seriously ill, whilst causing only mild/no disease in others, despite abundant viral replication in both. We will use in vitro and in vivo experiments to address our overarching hypothesis that the clinical fate of BTV infection is determined by the complex balance between virus replication in the face of the host’s innate and adaptive immune responses. The outcomes of this proposal will inform appropriate control strategies for this veterinary disease and generate an intellectual framework of value in understanding disease susceptibility in many other arboviral diseases of humans and animals.
Enhancing the catalogue of the scientific papers of Professor Alexander Haddow, 1912-1978 31 Dec 2016
Objectives: This cataloguing and preservation project will open up the research possibilities of the papers of Alexander John Haddow (1912-1978), entomological epidemiologist and key member of the investigative team who originally discovered the Zika virus. Details of work: The Project Archivist will improve access to the collection by providing an item-level on-line catalogue. This will allow users to discover the collections full research potential, not only of Haddow’s Zika virus research data, but also the data relating to many other mosquito-borne viruses found within the collection, including the Chikungunya virus. Primarily this will involve enhancing descriptions of the research data by indexing the viruses, vectors and data collection techniques used by Haddow and his colleagues. This will make them easily discoverable online to inexperienced users of archive collections like many in the scientific research community. To promote the collection’s long-term preservation, it will be repackaged in acid-free folders and boxes, and ferrous clips and staples will be replaced with brass paperclips. A detailed condition assessment of each item will be undertaken during cataloguing, and a preservation plan will be agreed with the Preservation manager. Taken together these two strands of work will prepare the collection for a future digitisation project.
Normative female sexuality and abortion stigma: a feasibility study using qualitative secondary analysis 24 May 2017
This project examines the relationship between female sexuality and the stigmatisation of abortion, directly addressing femininity, marginalisation and sexual/health rights. Worldwide, abortion remains controversial, and highly stigmatised, as it challenges powerful social norms of feminine sexuality, particularly in socio-cultural contexts where women’s moral autonomy is contested. A growing body of US-focused scholarship demonstrates that stigma, underpinned by health inequalities, creates barriers for women seeking essential healthcare, and contributes to the medical and social marginalisation of abortion. However, little is known about processes through which narratives of ‘deviant’ female sexuality contribute towards abortion stigma in the UK. We will test the feasibility of using qualitative secondary analysis of existing datasets, to synthesise knowledge of manifestations of abortion stigma in different UK jurisdictions. This approach, undertaken by an interdisciplinary team with significant expertise in abortion research and provision, will explore the interface between feminine sexuality and abortion in the narratives of women, providers, educators, and wider society. The study is timely given the potential impact of ongoing political change on abortion provision. This preparatory/scoping work is essential in establishing the feasibility of a larger collaborative proposal that will incorporate additional datasets, and utilise this foundation to develop a stigma-reduction intervention.
The role of innate immune regulation in viral pathogenesis and the development of anti-viral T cell memory 11 Jul 2017
Immune mechanisms that regulate antiviral immune responses determine whether the host can control pathogen replication and virus-induced immunopathology. The pathogenic human cytomegalovirus (HCMV) establishes chronicity and induces inflammation-associated pathologies. Cytomegalovirus (CMV) also induces the largest known expansion of T cells, and thus represents an important tool for identifying mechanisms inducing robust T cell immunity. CMV may also be exploited as an attenuated vaccine vector. Using a CMV model of viral pathogenesis, I identified that immune regulation during initial infection determines the extent of virus-induced inflammation and development of long-lived virus-specific immunity. The key goals of this proposal are: Identify innate immune components that mediate viral pathogenesis and understand how they are controlled Test whether innate immune pathways can be a) safely targeted therapeutically to treat viral disease and/or b) used to predict genetic risk of CMV pathogenesis Identify the early immunological events that promote CMV-specific T cell memory development, and elucidate whether regulatory pathways controlling these factors can be harnessed to enhance virus-driven memory T cell formation induced by attenuated viral vectors This research will determine whether innate immune activation can be exploited to: 1) safely treat viral pathogenesis and/or 2) enhance virus-induced T cell memory responses.
Establishing objective measures for identifying children with Autism Spectrum Disorders using eye-tracking technology in the UK and India 09 Nov 2016
Autism Spectrum Disorders (ASD) contribute significantly to total years lived with disability globally. Most people with ASD in low-income countries are belatedly or never diagnosed, mainly due to the paucity of mental health specialists - hence critical years for treatment are missed. Objective measures for ASD detection are needed. Multiple cognitive markers of ASD have been identified using eye-tracking technology; testing these markers in combination holds promise for effective identification of children with ASD. This proposal aims to establish objective measures for identifying children with ASD using eye-tracking technology in high and low-income settings. Stage 1 will analyse existing eye-tracking data from the British Autism Study of Infant Siblings, to establish a combination of eye-tracking tasks that has the highest probability of identifying children with an ASD diagnosis. Stage 2 will be a case control pilot study to determine whether the same combination of markers identifies children with an ASD diagnosis in India. The feasibility and acceptability of these eye-tracking tasks will also be assessed in an Indian context. Establishing effective, acceptable and feasible methods for objectively identifying children with ASD will improve detection in these settings and translate into a greater number of children benefiting from early interventions worldwide.
Improving life chances & reducing child health inequalities: harnessing the potential of existing data 24 Jan 2017
I will address three questions crucial to tackling child health inequalities (HIs): What factors lie on the causal pathway between socio-economic circumstances and children’s health and parental health-related behaviours, and which are most likely to reduce HIs? Who: Can we better predict those most likely to develop poor health (and will this help to target interventions more fairly and efficiently)? How: To what extent can early years’ interventions, if rolled out at different scales (e.g. to everyone, those living in deprived areas, those at greatest risk), reduce HIs? Cutting-edge methods, and the novel application of traditional methods, will be applied in two complementary data sources: linked administrative data (in Greater Glasgow and Clyde – the UK’s largest health governing board and subject to the highest HIs in Western Europe) and three UK cohorts (Millennium Cohort Study, Growing Up in Scotland, Southampton Women’s Survey). Several aspects of child health (motor, social, cognitive and motor development; thinness, overweight and obesity; unintentional injuries) and parental health-related behaviours (immunisation; breastfeeding; smoking) will be examined. Maternal mental health, childcare and parenting will be investigated as mediating mechanisms that are amenable to intervention through early years’ services. Findings will inform local and national policy and practice.
The project will focus on understanding critical aspects involved in the biology of the apicomplexan parasite Toxoplasma gondii (T. gondii), an obligate intracellular parasite that can infect every warm-blooded animal including humans. T. gondii, the causative agent of toxoplasmosis, is of medical importance for human health as an infection can cause severe damage in the developing foetus and immunocompromised persons. In addition, T. gondii serves a model organism for Plasmodium falciparum, the aetiological agent of malaria. In order to invade the host cell apicomplexan parasites rely on their acto-myosin system. Furthermore, recent research highlights the importance of parasite actin during intracellular parasite development. It is thus important to identify and characterise factors involved in the regulation of actin dynamics. Here, cutting edge molecular tools including conditional CRIPSR/Cas9-systems will be applied to screen a subset of essential genes in T. gondii for novel factors involved in the regulation of actin dynamics. Investigating how the parasites regulate these filaments will give valuable insights into how apicomplexan parasites establish infections in their host.
gammadelta T cells are immune cells, which express a T cell receptor whilst behaving like innate immune cells. There are two main subsets of gammadelta T cells in mice. CD27+ (IFNg-producing) gammadelta T cells are anti-tumourigenic, whilst CD27— (IL-17-producing) gammadelta T cells are pro-tumourigenic. However, the function of the anti-tumourigenic properties of CD27+ gammadelta T cells are not entirely known. Previous studies have shown that CD27+ gammadelta T cells kill cancer cells using the NKG2D receptor that binds stress signals that are not normally present in healthy tissue. The key goal of this project is to determine whether CD27+ gammadelta T cells kill BRCA1-deficient cancer cells through the NKG2D receptor due to the expression of stress ligands on the cancer cells. BRCA1 is a protein involved in DNA damage repair. My host lab has found that BRCA1-deficient breast cancer cells upregulate NKG2D ligands, suggesting that increased DNA damage leads to expression of stress signals. To address this goal, we will use techniques including western blot and flow cytometry following co-culture of CD27+ gammadelta T cells with cancer cells. It is hoped that robust T cell therapy will become a reality once we better understand the mechanisms of gammadelta T cells.
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.
The G protein-coupled receptor GPR35 in cardiovascular disease: downstream signalling, functional selectivity and potential as a therapeutic target 17 Jan 2014
G protein-coupled receptors transduce extracellular signals to cytoplasmic G proteins and other adapters. G protein-coupled receptor 35 (GPR35) has been associated with various diseases, including cardiovascular disorders such as hypertension, coronary artery disease and heart failure; however GPR35 is still poorly characterised and its precise role in disease remains unclear. The project will investigate the role of GPR35 in cardiovascular disease by addressing four key goals: Develop tools for the study of GPR35 activation. GPR35 and phospho GPR35 antibodies and G protein and arrestin selective GPR35 mutants will be generated. Determine the pathophysiological effects of GPR35 on the cardiovascular system. In vitro models of various cellular cardiovascular components will be used to assess migration, proliferation and hypertrophy in response to GPR35 modulation. The pathophysiological consequences of GPR35 modulation will be studied in vivo in a rat model of hypertension. Characterise a GPR35 knockout mouse. Blood pressure, vascular resistance andend-organ damage will be assessed in GPR35-deficient mice under basal conditions and following challenge with a range of pathological stimuli. Assess the role of G protein and arrestin dependent signalling pathways. Signalling downstream of GPR35 activation will be studied in cells expressing wild type receptor or G protein and arrestin-selective mutants.