- 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.
Scottish Consortium TMaT Programme: 'Characterising the development of chemotherapy induced peripheral neuropathy (CIPN) and assessing a novel TRPM8 agonist treatment, using functional magnetic imaging resonance (fMRI)'. 21 May 2012
We propose a first-class training programme to create a cadre of clinical academics withoutstanding TMT capabilities [Glossary:Annex-A], building on an established collaboration among internationally competitive scientists within four Scottish clinical academic institutions and a leading global pharmaceutical company, Wyeth (TMRC, value ~£50million). STMTI will focus initially on translational approaches to disorders of high priority in which considerable unmet clinical need remains, and where there is compelling opportunity for ‘pathogenesis-to-clinic’ transition. Thus, cardiovascular/metabolic, inflammation, musculoskeletal, neuroscience and reproductive health themes are proposed [Annex-B]. STMTI builds on a well-established collaboration among academia, industry, NHS and government, combining complementary strengths in drug discovery and the various stages of drug development. Critically, all relevant enabling tools – bioinformatics, genetics, proteomics, imaging, biomarker development and high- quality phenotyping – are available. STMTI employs established, well-developed and nationally networked clinical research facilities, and an associated Scottish-wide research education programme. STMTI thereby creates an innovative interdisciplinary TMT training programme that will allow seamless academic career progression for outstanding clinicians: from MSc certification to clinical PhD training, and onwards to academically-protected clinical lectureships. STMTI will place its fellows in an enviable and highly competitive position for a career in TMT and ultimate appointment to senior academic positions.
Calprotectin is released in neutrophil extracellular traps in response to infection and is central to CF lung inflammation. 25 Nov 2010
This research will elucidate a central role for calprotectin, and its release on NETS in the exagerated inflammatory response to persisting infection in the CF lung. Calprotectin may have a fundamental role in the pathophysiology of CF lung disease based on my previous findings that calprotectin is: 1. highly abundant in CF BALF and sputum; 2. a major constituent of NETs, and correlates with the levels of NETs in sputum; and 3. pro-inflammatory to primary human macrophages. I will now ans wer questions leading to a better understanding of inflammation in CF following infection and offer new therapeutic insights by utilising both clinical samples and animal models. Key Research Goals: 1. Assess NET production and calprotectin release following neutrophil interaction with bacteria in both CF and non-CF donor neutrophils, and demonstrate the pro-inflammatory potential of NETs containing calprotectin in-vitro. 2. Evaluate the induction of NET production and calprotectin release in wild type and CF models of infection. 3. Elucidate a central role for calprotectin in the inflammatory response in wild type and CF models of infection. 4. Intervene therapeutically in CF models by neutralising calprotectin (monoclonal antibody therapy) or increasing NET clearance (nebulised DNAse) and evaluate similar in clinically relevant samples.
Ribosome maturation involves hundreds of ribosome assembly factors (AFs) that regulate the time-wise association of ribosomal proteins. Although the RNA is the catalytically active component in ribosomes, the ribosomal proteins play crucial roles in rRNA folding and maintenance of long-range rRNA interactions.Intriguingly, preliminary structure probing data from the lab revealed that AFs required for the formation of the 40S head domain dramatically alter the interactions of ribosomal proteins with rRNA, several of which appeared misplaced in the 40S assembly intermediates. This misplacement presumably has a major impact on the overall structure of the rRNA. We hypothesize that AFs function by preventing certain ribosomal proteins from adopting their final conformation in 40S intermediates until final rRNA processing and folding steps have been completed. The proposed work aims to understand the mechanism and functional importance behind this initial misplacement by addressing (i) how this affects the global structure of the 18S rRNA, (ii) how this is linkedto 18S rRNA maturation and (iii) by dissecting the ribosomal protein-rRNA interactions required for the 18S rRNA maturation. The outcomes should provide substantial novel insights into the function of AFs in ribosome remodelling and rRNA folding.
Deprotection of cohesion in meiosis II 12 Jul 2011
The faithful segregation of chromosomes requires the cohesion of sister chromatids, a function mediated by the cohesin complex. In mitosis, cohesin iscleaved in one step along the length of the chromosomes to allow sister chromatid segregation. In meiosis, however, cohesin is cleaved in a step-wise manner. Cohesin at chromosome arms is cleaved in meiosis I to allow homologue segregation but protected around the centromeres until meiosis II, when its cleavage triggers sister chromatid segregation. How centromeric cohesin is "deprotected" to allow its cleavage during meiosis II is unknown. The overall aim of my project is to determine how pericentromeric cohesin becomes susceptible to cleavage in meiosis II. To do this, I will first identify post-translational modifications of cohesin in meiosis II and their role in allowing cohesin cleavage. Secondly, I will investigate how the cohesin protector Sgo1/PP2ARts1 is inactivated in meiosis II. I will determinethe behaviour of the protector throughout meiosis and investigate why it is lost from the pericentromere at the end of meiosis II. Furthermore, I will interactors and post-translattional modifications of Sgo1 and study how these affect its function. Overall, I will gain insight into the mechanisms governing the cohesin deprotection in meiosis II.
Regulation of microtubule nucleation is important for spatiotemporal control of microtubule distribution in eukaryotic cells and for many aspects of cell division and differentiation. Nucleation from both the centrosome and non-centrosomal sites involves the gamma-tubulin complex, but regulation of the gamma-tubulin complex is not well-understood. We will investigate this using fission yeast as a model system. We discovered two proteins, Mto1 and Mto2, that form a complex (Mto1/2) that both l ocalizes the gamma-tubulin complex to multiple intracellular sites and activates the gamma-tubulin complex to make it a functional nucleator. We will determine the molecular mechanisms by which Mto1/2 regulates microtubule nucleation by the gamma-tubulin complex, using a combination of genetics, microscopy, biochemistry/proteomics, in vitro functional assays and structural analysis. As the localization of Mto1/2 dictates where cytoplasmic microtubule nucleation occurs, we will identify the p roteins and mechanisms targeting Mto1/2 to distinct sites in the cell. To understand how Mto1/2 activates the gamma-tubulin complex from a mechanistic perspective, we will study the complexes in vitro, using a variety of methods, including functional reconstitution with purified proteins, chemical cross-linking and mass-spectrometry, and single-particle electron microscopy. Finally, we will address how the organization and localization of Mto1/2 is regulated by the cell cycle.
microRNAs and viral pathogenesis. 23 Jun 2009
miRNAs are small single-stranded RNA species of approximately 20-24 bases in length that regulate gene expression through post transcriptional mechanisms. We have used a biochemical approach to identify targets of miRNAs encoded by human cytomegalovirus (HCMV). This approach has already proven effective with the identification of multiple targets of one HCMV miRNA. These targets showed a striking over representation of genes involved in cell cycle control with predicted miRNA binding sites fo und almost exclusively within the 5 UTR. The assay will be used to screen all 11 HCMV miRNAs to gain valuable information on the function of viral miRNAs and miRNAs in general. The discovery of RNA interference has also proven to be a powerful tool for specific knock down of genes. However, toxic effects, bioavailability and cost have hampered in vivo use of small interfering RNAs. We have developed a system that allows highly effective, tissue specific, knock down of any viral gene using cel lular miRNA target sites. I will use this system to investigate the role of haematopoietic cells in CMV. This should also be a powerful approach for investigating a broad range of pathogenesis questions.
The role of presynaptic NMDA receptors in sensory information processing and cerebellar synaptic plasticity in vivo. 09 Dec 2008
Presynaptic glutamate receptors play a pivotal role in regulating synaptic neurotransmission throughout the CNS. However, little is known about how these receptors regulate neuronal network activity or experience-dependent learning in the intact brain. To address these issues I will investigate the role of presynaptic NMDARs during information processing and synaptic plasticity in the cerebellar cortex in vivo. Specifically, I would like to know: Can presynaptic NMDARs modulate excita tory and/or inhibitory synaptic input to single molecular layer interneurons in vivo? What are the functional effects of presynaptic NMDAR activation on Purkinje cell spike output? Are presynaptic NMDARs involved in cerebellum-dependent motor learning in awake, behaving mice? What insights can be gained from exploring the functional consequences of presynaptic NMDAR activation at the single neuron and functional network level? To a ddress these specific questions I will use a combination of in vivo and in vitro whole-cell patch-clamp recording techniques, selective pharmacology, conditional NR1 knock-out mice and computational modelling. A key goal of this proposal will be to develop whole-cell patch-clamp recording in awake, behaving mice. This newly developed technique will undoubtedly provide a new vista on the mechanisms involved in experience-dependent learning.
Existing methods for allowing the statistical programming language R to use High Performance Computing (HPC) resources require specialist knowledge of parallel programming in order to handle common analytical tasks such as correlation between all variables in a dataset. The technology proposed here is a user-friendly software suite to enable biological researchers to more easily exploit supercomputers or even a cluster of personal computers to run computationally expensive R scripts. This will e nable researchers to use R/Bioconductor to perform extensive statistical and combinatorial analyses of high-dimensional biological data otherwise considered intractable. This intractability is in part due to the necessity for in-depth knowledge of HPC programming techniques which are rare to non-existent amongst biological researchers. This software will produce a step change in both the complexity and size of analysis that can be performed in a reasonable time as well as significantly reduce the execution time for existing analyses on current bioinformatics computational infrastructures. Development will proceed in tandem with research that will use the software to exploit HPC to conduct new combined analyses of previously studied datasets. This will ensure the resulting application contains the functionality immediately relevant to biological research groups and importantly, is easily usable by such researchers.
TGF-beta is a major pro-fibrogenic cytokine and therefore mechanisms that regulate TGFbeta signaling within the liver are likely to play a critical role in liver fibrogenesis. Integrins represent a major mode of communication between the matrix, inflammatory cells, fibroblasts and epithelia. The alphavbeta8 integrin has the potential to bind the RGD sequence in the latency associated peptide (LAP) of TGF-beta1 and -beta3 and activate latent TGF-beta. We hypothesise that the integrin alphavbeta8 is a major regulator of TGF-beta activation during hepatic fibrogenesis, and that inhibition of alphavbeta8-mediated TGF-beta activation will result in reduced activation of latent TGF-beta, decreased myofibroblast activation and liver fibrosis. Aims: 1) To determine which cell types express alphavbeta8 in normal and injured liver. 2) Using genetic approaches (inducible and tissue specific deletion of alphavbeta8) in liver fibrosis models to dissect which cell types are important regulators of h epatic alphavbeta8-mediated TGFbeta activation. 3) Measurement of alphavbeta8-mediated TGFbeta activation by HSC, and analysis of HSC phenotype following manipulation of alphavbeta8 expression. 4) To determine how alphavbeta8-mediated TGFbeta activation is regulated in hepatic stellate cells. These studies should facilitate the development of new anti-fibrotic therapies by clarifying the mechanisms that regulate TGFbeta activation in hepatic fibrogenesis.
The need for the immune system to maintain a broad T cell repertoire without developing an over-zealous reactivity to self antigens leading to autoimmunity is clear; this is broadly achieved through central and peripheral tolerogenic mechanisms with a huge amount of research being undertaken in recent years on the role of regulatory T cells in the maintenance of self tolerance. However, T cell adaptive tolerance, where a T cell senses antigenic cues from its environment and adjusts its threshold for full activation accordingly, has recently been shown to be an important tolerogenic mechanism yet has received little attention to date. The aim of this project is to more fully explore the mechanism of T cell adaptation. In particular, the longevity of the adapted T cell phenotype will be established and the role of CD5, which has been implicated as a potentially crucial molecule in adaptation, will be explored. In addition, how adapted T cells differ in their interactions with anitgen pre senting cells will be studied by multi-photon microscopy. Together, these studies will be valuable in clarifying the mechanism of T cell adaptation and the findings are likely to be highly relevant in our understanding of the maintenance of self tolerance.
Due to the link between metabolism and alternative activation in macrophages discussed below we seek to address the following questions: l What is the role of IL4/ IL13 signalling via the IL4R? chain in induction of alternatively activated macrophages (AAM?) by helminths in vivo? l Do helminthinduced AAM? upregulate a metabolic regime biased towards fatty acid oxidation (FAO)? l What transcriptional processes link the metabolic and immunological components of AAM?? l To what extent is PPAR? involved in the induction and maintenance of AAM? in vivo?
Alternative activation of dendnitic celis. 16 Jun 2008
To determine how dendritic cells (DCs) are alternatively activated and how pathogens influence this process. 2) To investigate the impact of alternative activation of DCs on their activation and function. 3) To compare the activation status and function of alternatively activated DCs with alternatively activated macrophages (AAMØ).