- 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.
We propose to establish a new facility for anaerobic protein crystallisation and single crystal micro-spectrophotometry at Leicester. This facility will be critical to developing new research strategies to enable us to explore protein mechanisms within three major biological areas of interest at Leicester (many of which are WT funded): (i) Regulation of gene expression (ii) Redox enzymology of important iron-dependent enzymes (iii) Key enzymes of pathogenic microorganisms. This integrated, multi disciplinary facility will be a significant advance; it will have multiple users within Leicester and will be made available to others, since such facilities are not accessible elsewhere. The technical expertise that is needed to support this new facility is already available on-site and the new facility will form part of the on-going, long-term investment in structural biology at Leicester.
The research will develop methods pioneered in the department to precisely analyse sequence variation between different copy number haplotypes of the FCGR3 gene, and to infer recurrent ectopic recombination breakpoints between the FCGR3A and FCGR3B repeats. This information will inform assays designed to assess the frequency of de novo deletion and the amount of somatic copy number variation at this locus. Key goals are: 1. A sequence-level catalogue of coding and non-coding sequence variatio n of the FCGR3A and FCGR3B repeat haplotypes using genome fractionation by pulsed-field gel electrophoresis followed by high-throughput sequencing, distinguishing differences between paralogues from allelic differences. 2. Identification of historical ectopic recombination breakpoints in 45 deletion copy number haplotypes from this sequence catalogue. 3. Development of an assay to specifically amplify de novo deletion haplotypes from genomic DNA. 4. Use this assay to determine frequency of d e novo deletion in sperm.
Investigation of the role of protein phosphorylation in the erythrocytic stage of the human malarial parasite Plasmodium falciparum. 01 Oct 2009
This project is divided into three objectives: 1. To determine the global phospho-proteome in the schizont stage of P. falciparum. 2. To establish the phosphorylation networks regulated by specific protein kinases that are essential for parasite viability. 3. To determine the role of phosphorylation in parasite growth and invasion into red blood cells. Meeting these objectives is centred on the integration of three core approaches. The first is the application of biochemical/mass spectro metry techniques that will define the phospho-proteome of P. falciparum. The second is the use of a novel chemical genetics approach in combination with pharmacological inhibitors to inhibit specific protein kinases and thereby probe the molecular mechanisms by which phosphorylation contributes to parasite viability. Thirdly, the phosphorylation events discovered in this project will be set in a functional context by studying progression of the parasite through the erythrocytic cycle and parasit e invasion into erythrocytes. By combining these three approaches we aim to both further our basic understanding of the role played by phosphorylation in P. falciparum but also to contribute to the protein kinase based drug discovery programme being conducted in the Doerig lab (co-applicant).
Protein-protein interactions, domain motion and electron transfer in the cytochrome P450 mono-oxygenase system. 20 Feb 2008
In the P450 mono-oxygenase system, cytochrome P450 reductase accepts electrons from NADPH, a 2-electron donor, and transfers them one at a time at the appropriate points in the catalytic cycle of cytochrome P450s, which are central to the metabolism of drugs in man. We will use a multidisciplinary approach involving mutagenesis, NMR, SAXS, kinetics and chemical cross-linking to study the structure and function of membrane-bound cytochrome P450 mono-oxygenase complexes, specifically complexes con taining P450 3A4. Studies of appropriately designed mutants of cytochrome P450 reductase will allow us to refine our models for domain movement in the enzyme understand its role in electron transfer to the P450. We shall develop a structural model for the functional reductase cytochrome P450 complex in the membrane and relate the kinetics of formation and dissociation of this complex to substrate turnover by the P450 and the role of cytochrome b5. The results will allow us to develop, for the first time, a structural model of the P450 mono-oxygenase complex in a membrane and to relate this to the physiological electron transfers in this important drug-metabolising system.
The biological oxidation of L-tryptophan. 31 Oct 2007
Oxidation of l-trptophan in all biological systems is catalysed by heme dioxygenases. The heme dioxygenases add a completely new dimension to the overall scope of reactivities known to be catalysed within the heme protein family. With heme proteins being used so ubiquitously across in biology, the dioxygenases therefore represent important targets. We have access to four different heme dioxygenases (bacterial and human tryptophan 2,3-dioxygenases (TDO) and indoleamine 2,3-dioxygenases (IDO)) . Recent breakthroughs, including new structures, provide us with a perfect opportunity to at last gain a detailed molecular insight. The objectives are: 1. To map the catalytic cycles of human and bacterial TDO/IDO. 2. To functionally characterise human TDO. 3. To use our unique structural framework to examine the factors affecting substrate binding across the family. 4. To examine the redox properties and to correlate this to functional work. 5. To determine new structures in cluding ternary complexes and mutant enzymes. 6. To generate a suite of site-directed variants to feed into our functional and structural analyses. The project builds on our preliminary published work and we have all the infrastructure and expertise needed to meet our goals. We expect the work to have major impact at the international level.
The role of mast cell and airway smooth muscle interactions in the pathophysiology of asthma. 31 May 2012
We hypothesise that airway hyperresponsiveness and persistent airflow obstruction in asthma result from a) intrinsic abnormalities in airway smooth muscle (ASM) from asthmatics and b) interactions between ASM-mast cells. We aim i) to examine the differences between ASM from asthmatics and non-asthmatics and to determine the mechanisms underlying these differences interms of calcium homeostasis using single cell and FLIPR analysis; contractility using collagen gel contraction assays and single c ell measurements of maximal contraction and velocity; synthetic capacity using a variety of approaches including ELISA, immunoblotting, proteomics, qPCR and gene array; migration using 2D assays; proliferation by MTS assay and thymidine incorporation; and survival by Annexin V and PI staining, ii) to investigate in vitro the effect of ASM-mast cell interactions on ASM and mast cell function respectively and to confirm effects, as appropriate, in tissue and iii) to confirm that localisation of ac tivated mast cells in the ASM-bundle is a feature of asthma across severity of disease and to determine whether this is affected by corticosteroids or experimental viral infection. For the in vitro experiments we shall use freshly isolated and primary ASM cultures from bronchial biopsies from asthmatics and controls and primary mastcells from lung resection material.
Characterisation of P2X1 receptor function, regulation and development of molecular models of drug action at ATP gated P2X receptors 09 Nov 2006
ATP gated P2X1 receptor channels play important roles in the cardiovascular system contributing to the control of arterial tone as well as blood clotting and may be novel targets for the development of anti-thrombotic drugs. The aim of this proposal is to study the neuronal role, regulation and molecular properties of P2X1 receptors. (i) To address the role of P2X1 receptors in the nervous system we will generate a fluorescent P2X1-EGFP knock-in reporter mouse to identify and characterise the receptor in live cells. (ii) P2X1 receptors are expressed in lipid rafts, phosphorylated and sensitive to the intracellular environment. We will determine the extent and mechanisms of P2X1 receptor regulation by other receptors, the contribution of the intracellular domains to channel function and identify the role of interactingproteins in modulating receptor properties. (iii) We have used a mutagenesis approach to identify conserved residues in the extracellular domain that are involved in ATP action, however the pharmacological differences between subunits suggest that variant amino acids are also important in drug binding. We aim to use cysteine scanning mutagensis and analysis of the site of binding of cross-linked ATP analogues to develop molecular models of agonist and antagonist action at P2X receptors.
Processes of human meiotic recombination. 01 Nov 2006
We are using single molecule methods to access recombinant DNA molecules directly in sperm, to characterise basic features of human meiotic recombination such as clustering of exchanges into hotspots, identification offactors that control hotspot activity and the role of hotspots in driving genome instability. However, these studies have sampled very few hotspots in the human genome and the potentially most informative sites for investigating recombination have yet to be characterised. Also, sperm analysis gives information on resolution sites in meiotic recombination, but not on recombination intermediates. This project will therefore identify the most active hotspots in the human genome and will use these as a resource not only to explore hotspot properties but also to directly access intermediates in therecombination process. Targets include the recovery of resection tracts extending from recombination-initiating double strand DNA breaks in testis andthe isolation of later intermediates in the recombination pathway. This will give direct information on DNA processing during human meiotic recombination, including the location of initiation sites, resection tract lengths and distributions, and the location of Holliday junctions. We will also use these and other hotspots to test directly whether recombination is base mutagenic.
Streptococcus pneumoniae causes a very high number of cases of pneumonia, meningitis and bacteraemia, worldwide. Despite using antibiotics that kill the bacterium, a large number of patients still die and in meningitis, many survivors have profound neurological handicap. This is because the bacterium produces a very damaging virulence factor that is not inhibited by antibiotics. This problem constitutes an unmet medical need that Professor Peter Andrew and colleagues from the University of Leicester are proposing to fulfill. They have identified that small molecules can inhibit this virulence factor and are effective in vivo. The team have been awarded funding through the Seeding Drug Discovery initiative to identify new small molecules and through a programme of medicinal chemistry, combined with in vitro and in vivo testing, to identify lead compounds with appropriate efficacy, pharmacokinetics and toxicology. The aim is that giving such molecules will reduce the number of patients that die or suffer handicap as a result.
The majority of the malignant tumours contain mutations in p53 resulting in the expression of a mutant p53 protein. This protein has not only lost its transcriptional tumour suppressive functions, but has also gained novel functions in driving metastasis and developing resistance to chemotherapy. To a certain extent these novel functions comprise mutant p53s ability to inhibit other transcription factors, including p63. The overall aim of my research program is to better understand the processes underlying mutant p53 gain-of-function in invasion and chemo-resistance. The key goals of my proposed research are: (1) To further characterise the inhibitory role of mutant p53 on p63. (2) To explore the role of mutant p53 in the regulation of Dicer (a target gene of p63) and microRNA biosynthesis. (3) To characterise the role of mutant p53 (and loss of p63) in chemo-resistance and to demonstrate a role for multidrug receptor recycling in chemo-resistance. (4) To assess the role of the mic roenvironment in the behaviour of mutant p53 cells to chemo-therapy.