- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 18 Jan 2019
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
LifeLines 20 Apr 2016
This is the expansion of a project supporting volunteers aged 50 plus to run activities for vulnerable older people to improve health and well-being. These have previously included art classes, creative writing, yoga and computer club. The group will expand across the city, recruiting more volunteers, supporting more than 800 new people and establishing a Menâ€™s Network to encourage older men to socialise regularly. It will also extend its HealthLink scheme to help older people get to medical appointments.
Kilkeel RBL - Saving Our Community Venue 22 Oct 2015
The group is a community and voluntary based organisation providing a range of services and activities to the local community. They received a grant of Â£10,000 to make improvements to their venue so that it can be used for more classes and activities.
Towards improving access and facilities for disabled people at the Forest Hall Ex-Servicemen's Institute.
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.
CMV accounts for 40% of CD8 and 10% of CD4 T cells in healthy seropositive individuals. The ubiquitous nature of CMV gives a lifetime infectivity of 70%. CLL is associated with immune suppression, enhanced further by chemotherapy treatment. CMV specific CD4 and 8 T cells are increased in CLL compared to healthy individuals and even more pronounced following chemotherapy, hypothesised to be secondary to subclinical viral reactivation. This further impacts on the general immunosuppressive state of CLL seropositive patients, leaving a reduced polyclonal T cell repertoire to provide immunity. Associated with this finding is a significant increase in morbidity in those seropostive with CLL compared to those CMV negative and a hypothesis that the virus also impacts on overall survival. This project will investigate if the increase in CMV specific CD4 T cells is corresponding with subclincal viral reactivation (PCR of lytic and latent viral antigens) and using HLA class I and II tetramers the specificity of the CD4 and 8 T-cell response seen. These T cell subsets will also be analysed for their membrane phenotypes and functional properties using multiparametric flow cytometry to determine cytokine production and compare to healthy controls. The study will also investigate the role of natural killer cells and gamma delta T cells to improve knowledge of CMV- specific immunity. Correlation of serostatus and survival will take place and if significant an antiviral clinical trial will be instigated. Ultimately this PhD project will correlate these immune findings with clinical findings.
Synovial fibroblasts (RA SFb) drive disease persistence and joint destruction in RA. They are characterised by a persistent in vitro invasive phenotype. It is not known how or when this phenotype is generated during the evolution of RA, but preliminary work suggests that epigenetic modifications play an important role. Increasing evidence for a therapeutic early window in the first few months of RA implies that such modifications may not be fully established early in disease. We will test the hypothesis that the persistent RA SFb phenotype is determined by epigenetic regulation of gene transcription and that epigenetic marks will differ in fibroblasts from patients in different outcome groups in the very early stages of inflammatory arthritis. Objectives: To compare transcriptional profiles of SFb from patients in four different clinical outcome groups (very early arthritis that becomes RA, very early arthritis that resolves, established RA, normal) To determine the genome wide presence of histone marks of stable gene activation (H3K4me3) and repression (H2K27me3) in SFb from patients in those four groups To correlate the presence of activating and repressing histone marks with gene expression To explore the functional significance of these findings using gene ontology and pathway analyses, and in vivo functional assays
Structure and function in desmosomal junctions. 15 Mar 2011
Our overall goal is to elucidate the structural mechanisms of the desmosomal proteins in sufficient molecular detail to understand their specific roles in skin and heart disease and wound healing at a level which informs rational diagnostic and therapeutic design. The project will build on our previously published work on the structural biology of the desmoglein cytoplasmic domain and will address three novel areas of desmosome biology. First, it will highlight the role of intrinsically disord ered regions and inducible structures in the interactions of proteins and conserved elements within the desmosome using circular dichroism and nuclear magnetic resonance (NMR) spectroscopy. Second, it will show that desmosomal proteins exhibit differential interactions with each other by mapping the binding specificities and stochiometries of complexes within tissue-specific systems by surface plasmon resonance detection and analytical ultracentrifugation experiments. Finally, we will solve th e solution structure of the plakin domain of desmoplakin, and show for the first time the effects of human ARVC mutations at the molecular level using NMR and small angle X-ray scattering alongside quantitative binding studies. Together this will provide a more comprehensive, structural biological view of the cytoskeletal machinery that dictates cell adhesion and signaling within the desmosome.
Neurotrophin, Toll and Trk-like functional relationships in the Drosophila central nervous system. 09 Mar 2011
Building on our discovery of Drosophila neurotrophins (DNTs), we aim here to identify the DNT receptor repertoire. Our preliminary data have revealed that DNT1 and DNT2 most probably bind Toll6 and Toll7 receptors, and might also bind p75-like and divergent Trk-like receptors whose evolution may have involved the separation of receptor modules. Drosophila Toll and mammalian Toll-like receptors (TLRs) are involved in innate immunity, while mammalian NTs link nervous system structure and function from development to cognition. There are potential functional overlaps between NTs and TLRs, since mammalian NTs are also involved in immunity, and TLRs have functions in the central nervous system (CNS). It is compelling to find out to what extent the NT and Toll protein families functionally interact, and what the full receptor repertoire is available to NTs in fruit-flies. This is essential in order to continue using Drosophila to understand the brain and to model human brain diseases. The key goals are: Objective 1 To investigate with genetic in vivo analyses the functions of Toll6 and Toll7 in the Drosophila CNS. Objective 2 To test biochemically if Toll6 and Toll7 function as DNT receptors. Objective 3 To test p75-like and Trk-like receptors as candidate DNT receptors.
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) whose pathogenesis is widely accepted to be T cell-mediated, one possibility being that exposure to infectious agent(s) in certain individuals induces T cell responses that cross-react with epitopes derived from self-proteins expressed in the CNS. One prime candidate in this regard is Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis (IM), a T cell-mediated immunopathologic disease which itself predisposes to MS. Recent reports suggest that T cell responses to one EBV antigen, EBNA1, differ in their fine specificity between MS patients and healthy controls, and include T cells that cross-recognise myelin-derived epitopes. Using our experience in EBV immunology, we plan to address these issues in more detail: (1) analysing the frequency, epitope range and autoreactive potential of EBV-specific CD4+ and CD8+ T cells in the blood of MS patients versus healthy controls with and without a history of IM, (2) determining the autoreactive potential of recently-identified CD4+ T cell responses against cellular antigens up-regulated in EBV-infected cells, (3) cloning T cells specific for central nervous system (CNS) protein epitopes from the cerebrospinal fluid (CSF) of selected MS patients and examining their potential for EBV-crossreactivity.
Selection mechanisms in the thymus fail to remove all T cells that recognize tissue-expressed self proteins. Self-reactive T cells capable of autoimmune damage are therefore present in the periphery. Continual recirculation of such cells through blood and lymphatics poses no danger to the host. However, if such cells gain access to the self-antigen bearing tissue, immune-mediated damage becomes a possibility. Our laboratory has developed a transgenic model in which the factors that control th e entry of self-reactive T cells into the target tissue can be dissected. We have mice bearing T cells specific for a pancreatic antigen that fail to enter the pancreas. We have found that we can trigger T cell infiltration of the pancreas by a single injection of B1 cells. This proposal seeks to identify the mechanism by which B1 cells trigger tissue infiltration. We will test whether B1 cells act directly on T cells, whether they modify vessels within the tissue to allow T cell access, and whether they have an intrinsic capacity to initiate the formation of ectopic lymphoid tissue. We will also identify the timeframe in which B cell depletion is beneficial during the onset and progression of autoimmunity.
Artworks, inspired by Darwin's iconic description of the development of the eye, will be produced and form the centrepiece for public engagement activities in the Year of Darwin 2009 and beyond. The proposed series of paintings draws on novel biomimetic materials and methods that mirror the process of evolution. Latest iridescent nano-particles and innovative casting techniques are employed to arrive at successively 'modified' variations of the 'same' painting. The complex interrelationships between the evolution of colour, display, camouflage and perception in nature and art are explored. Evolutionary theory, molecular genetics and the emerging field of Evolutionary Development Biology ('Evo Devo') link the artistic and scientific concepts.
A SkyScan 1172 microcomputer tomographer. 08 Jul 2008
The School of Dentistry wishes to obtain a SkyScan 1172 microComputer Tomographer (microCT) to enable non-destructive 3D imaging and densitometric analysis of hard and soft tissues. This is a combined proposal from applicants in Dental Tissue Injury & Repair, Biomaterials, Oral Pathology and Dental Ultrasonics. Cutting edge research projects are on-going in all these areas and between disciplines. Preliminary data, generated using equipment at a distant site, has demonstrated the utility of micr oCT for the School s research portfolio. In-house equipment would therefore enhance on-going projects, specifically addressing issues in areas of dental and bone mineralization, novel dental material development, mechanisms of oral pathogenesis and the clinical application of dental devices. Notably, technical advances mean that the microCT model requested supersedes the one previously utilized enhancing its analytical ability. In addition, if this application was successful, microCT instruction would become embedded in our postgraduate and staff research training programmes. This application addresses several aims of the Wellcome Trust by making key contributions to the creation, development and maintenance of major dental research resources. Ultimately we anticipate that the potential outcomes from its use would lead to translational benefits for oral and dental healthcare.
'Regulation and dysregulation of immune cell signalling in the hypoxic inflammatory environment'. 21 Apr 2009
The oxygen tension in inflammatory sites, such as the synovium in rheumatoid arthritis, is very low. Our hypothesis is that this hypoxia perpetuates inflammation by promoting the production of reactive oxygen species (ROS) which damage proximal signalling molecules particularly protein tyrosine phosphatases (PTP), resulting in altered signalling and differentiation. Additionally, we will investigate how this process interacts with more established hypoxic pathways such as stabilisation of HIF-1?, to regulate the signalling and responses of immune cells in chronic inflammation. We will: 1. Investigate how hypoxia alters CD4 T lymphocyte signalling and differentiation with a particular emphasis on proximal signalling regulation by phosphatases. 2. Determine the effects of hypoxia on the differentiation and function of macrophages and dendritic cells and their ability to polarise T cell responses. 3. Determine the effects of hypoxia on the production and function of regulatory T cells. 4. Establish whether the function of the autoimmune-associated R620W variant of the PTP Lyp is affected by hypoxia-induced damage thus promoting dysfunction and loss of immune tolerance.
Ocular Mucous Membrane Pemphigoid (ocMMP) is a type II autoimmune disease affecting multiple mucous membranes including the eyes and the mouth. It is a blinding acquired immunobullous condition, characterised by targeting of mucosal basement membrane zones (mucBMZ) by autoantibodies, resulting in inflammation, blistering and scarring (fibrosis). Although ocular inflammation can be controlled with systemic immunosuppression, 50% of patient's disease will progress and 1 in 8 will become legally blind. The project aims to test the hypothesis that progressive fibrosis in mucous membrane pemphigoid, occurring in the apparent absence of clinical inflammation, is driven by underlying inflammatory processes. A prospective study of patients with MMP with a minimum follow-up of 12 months (60 existing MMP patients and 10 new patients per year) will be undertaken. This will be in collaboration with Mr. John Hamburger (Senior Lecturer/Consultant in Oral Medicine) at the University of Birmingham School of Dentistry. There will be three monthly longitudinal clinical assessments of inflammation and cicatrisation (fibrosis). Characterisation and & comparison of the local microenvironment of the eye & the mouth in MMP (tears and saliva) will take place. This will include analysis of anti-mucBMZ antibodies, inflammatory cellular infiltrate and cytokine profiles. Comparison of differences between local microenvironment and peripheral blood, correlation of clinical & local microenvironment parameters and comparison of differences with other cicatricial diseases will be undertaken. We hope to demonstrate that progressive fibrosis in mucous membrane pemphigoid, occurring in the apparent absence of clinical inflammation, is driven by underlying inflammatory processes. The results could provide diagnostic, prognostic and potentially therapeutic information for patients with MMP.
This application aims to establish (i) the very early events that underlie signalling by the three platelet ITAM receptors, GPVI, CLEC-2 and FcgammaRIIA, and (ii) the physiological and pathological roles of CLEC-2. ITAM receptors signal through sequential activation of Src and Syk tyrosine kinases, initiating a signalling cascade that leads to cell activation. The major goals of this proposal are (a) to identify the Src kinases in human and mouse platelets that mediate phosphorylation of pl atelet ITAM receptors; (b) to compare the regulation of Syk by platelet ITAM receptors; (c) to determine the molecular basis of activation of Syk by a single YxxL sequence; (d) to study the spatial and temporal nature of the protein-protein and protein-lipid interactions that underlie the very early signalling events by platelet ITAM receptors using FRET and TIRF microscopy, and (e) to determine the functional role of CLEC-2 using CLEC-2 knockout mice or mice which express a non-signalli ng mutant of CLEC-2 that retains the ability to bind to its endogenous ligand, podoplanin. These studies will focus on tissues that express CLEC-2 and podoplanin, and on a possible role of the interaction of podoplanin to CLEC-2 in cancer metastasis.
DHEA is the major precursor of androgen synthesis via the classic pathway unless inactivated to DHEAS by DHEA sulfotransferase, which requires the universal sulfate donor PAPS for catalytic activity. We have identified inactivating mutations in PAPSS2 encoding PAPS synthase 2 in a girl presenting with premature pubarche followed by development of PCOS. These findings have established PAPSS2 deficiency as a novel monogenic cause of androgen excess, revealing DHEA sulfation as a gatekeeper to huma n androgen synthesis. In this project we will aim to identify and characterise further PAPSS2 mutations in patients with premature pubarche and PCOS, also exploring the possibility of novel mutations in other elements of the DHEA sulfation system. Taking a cell-based in vitro approach we will seek to identify novel pre-receptor mechanisms involved in the regulation of DHEA sulfation, including enzymes and transporters. Finally, we will examine whether common genetic variation in PAPSS2 contribut es to PCOS susceptibility by performing dense tagSNP genotyping in large PCOS and control cohorts. Taken together, this research project will investigate the physiological and clinical significance of a crucial metabolic pathway, with its impact extending beyond steroidogenesis and androgen excess to impaired sulfation in liver, bone and steroid-dependent tumours.