- 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
Dissecting and disrupting Epstein-Barr virus transcription initiation and elongation during latent infection. 09 Feb 2006
This research will test the hypothesis that the switch from W to C promoter usage during initial EBV infection represents a switch from non-processive transcription to EBNA 2-activated CDK9-dependent processive transcription necessary for the efficient production of the long primary transcript and the establishment of latency. We will also investigate whether the requirement for CDK9 for the efficient activation of transcription by EBNA 2 makes the anti-cancer drug and CDK9 inhibitor, Flavopiridol, an effective anti-EBV agent. Additional studies will further dissect the way in which pol II phosphorylation is regulated by EBNA 2. Key goals 1. Determine whether EBNA 2 stimulates transcriptional elongation in addition to initiation. 2. Determine whether EBNA 2 activated transcription can be blocked using Flavopiridol. 3. Dissect how pol II phosphorylation is regulated by EBNA 2.
The Imp2 mRNA binding protein: Roles in morphogenesis and differentiation of the mammalian inner ear. 20 Oct 2005
The inner ear develops from the otic placode, a specialised patch of neuroectoderm adjacent to the developing hindbrain. A major goal is to understand the molecular mechanisms that convert this patch of cells into the complex adult structure. IGF signalling is associated with inner ear development, but how inner ear IGF activity is controlled is not known. Previously we isolated the Igf2 mRNA binding protein, Imp2, and have shown it is expressed in different sensory epithelia during development, including the inner ear. In this project we will use gain and loss of function approaches in transgenic mice to determine the function of Imp2 in inner ear development. We will test the hypothesis that Imp2 is a key regulator of IGF activity, controlling morphogenesis and differentiation in the developing inner ear. Key Goals: Determine whether Imp2 regulates localised differential growth of cells in the otic epithelium Determine whether Imp2 affects hair cell differentiation Determine the effects of Imp2 on IGF1 & IGF2 expression Determine whether Imp2 regulates otic neuroblast proliferation and/or migration Determine the fate of Imp2 expressing cells in the mature inner ear Investigate the association of Imp2 with hair cell repair/regeneration
Computational and psychophysical studies of polarity effects in human visual motion processing. 28 Jun 2007
There is currently one widely accepted computational model of the earliest stages of visual motion processing in the brain, known as the motion energy model. Recent psychophysical and physiological results are inconsistent with the model, particularly with regard to responses dependent on the sign of luminance polarity. The proposal aims to develop and test a revised computational model of motion analysis. There are three key goals: 1) The first goal is to develop the revised model and establis h whether it can account for the basic capabilities of human motion perception. 2) Some perceptual effects are consistent with motion processes that respond to both signs of contrast polarity, others are consistent with processes that respond to only one sign of contrast polarity. The second goal is to determine whether the revised model can accommodate both kinds of effect. Predictions will be generated and tested in a series of psychophysical experiments. 3) Perceptual adaptation is a promin ent feature of motion processing, but previous models do not incorporate adaptation. The third goal is to establish whether the revised model provides an adequate explanation of perceptual adaptation.
At the current time, only a small proportion of the genetic risk of Wilms tumor is explained by known factors. It is likely that much of the residual risk is mediated by common variants that each confers a modest increase in risk. Our key goal is to conduct a genome-wide association scan to identify such Wilms tumor susceptibility alleles. In the GWAS, 2000 Wilms tumor cases will be genotyped for 660000 SNPs and genotypes will be compared with existing data on 6500 geographically-matched con trols. Any loci showing strong evidence of association after the GWAS will be fast-tracked for immediate verification by Taqman. Additionally, we will test 1536 SNPs from the ~1000 regions showing the strongest associations in 2000 additional cases using a custom assay. These genotypes will be compared to data available on an additional 6500 geographically-matched controls. Power calculations indicate we have at least 80% power to identify any locus conferring a per-allele risk of 1.25, pro viding the allele frequency is at least 20%. By additionally genotyping DNA from both parents of 1000 cases, we will investigate parent-of-origin effects for all confirmed loci and the 150kb critical region involved in control of IGF2 imprinting.
Inhibitors of Lysyl Oxidase for the Prevention and Treatment of Invasive and Metastatic Cancer 30 Mar 2009
Inhibitors of Lysyl Oxidase for the Prevention and Treatment of Invasive and Metastatic CancerThe enzyme lysyl oxidase (LOX) regulates cross-linking of structural proteins in the extracellular matrix.LOX also plays a role in stimulating the metastatic spread of cancer through the body. Its expression is increased in hypoxic cancers and is correlated with tumour metastasis and decreased patient survival. In model systems its inhibition significantly decreases cancer metastasis and increases survival. Since metastasis is responsible for over 90 per cent of cancer deaths these data validate LOX as an important therapeutic target in cancer. Professor Caroline Springer and Professor Richard Marais from the Institute of Cancer Research have been awarded Seeding Drug Discovery funding to develop drugs that target LOX. They are applying a medicinal chemistry drug discovery approach underpinned by a strong programme in LOX biology with the aim of producing orally available, small molecular weight drugs that inhibit LOX activity for cancer treatment.See our video: BRAF and cancer: collaborative drug discovery
A new class of genes containing small Open Reading Frames: cellular and molecular function of the encoded peptides. 06 Apr 2009
We have characterised a non-canonical gene, tarsal-less (tal). Tal is polycistronic and only contains small Open Reading Frames (smORFs) producing peptides as small as 11 amino-acids. These peptides function as a cell signal controlling gene expression and actin-mediated cell shape changes. I plan to ascertain the mechanisms for diffusion of these peptides and transmission of their signal by: A1) Investigating the mechanism of tal uptake in a cell culture assay; A2) Organising the proteins t hat bind tal (identified candidates and new ones to be searched for) in a pathway for the transmission of the signal; A3) Clarify the mechanism for tal-dependent transcriptional control; A3) Finding out how tal affects actin cytoskeleton. I also plan to search for more genes containing only smORFs in flies and other species, and to characterise a sample that will prove their existence as a class, and their general features, by: B1) searching for homologues of tal in distant species B2) characterising putative smORF genes we have already identified, to corroborate that their function is mediated by the small peptides they encode, and to obtain further information on their general structure and sequence signatures B3) searching for further smORF genes in flies, and finally in vertebrates
Prmtl has emerged as a critical factor for both transcriptIonal regulation and leukemogenesis, the objective of this project is to characterize the roles of Prmtl in hematopoietlc development. I reason that comprehensive analysis of the loss of function of Prmtl in hematopoietic stem cells (HSCs) and/or progenitors during different developmental stages will give important Insights into the normal functions of Prmtl, which will also provide crucial Information for development of strategies targeting Prmtl in human diseases.
Hippocampal synapses are now known to trade vesicles constitutively via an extrasynaptic mobile vesicle pool. This proposal will examine the regulation of this process in supporting the maintenance of synaptic structures, and examine whether vesicle trading can be utilized in a dynamic, activity-dependent manner to modulate synaptic efficacy. Vesicles will be labelled using GFP-based, photoswitchable, and activity-dependent fluorescent probes, and import/export dynamics examined using localized photobleaching/photoswitching techniques. Experiments will characterize cellular/molecular factors contributing to constitutive vesicle sharing under steady-state conditions. Activity-dependence of vesicle exchange will be tested by combining imaging with global or localized synapse-specific stimulation. These approaches will also be used to evoke forms of LTP-like long-term plasticity to test whether presynaptic vesicle pools locally recruit vesicles to undergo long-term remodelling, or build n ew functional release sites. The detailed changes associated with activity-dependent remodelling will also be examined by correlative fluorescence-ultrastructural analysis. Experiments will be performed in culture, but also in acute slices to establish the functional relevance of this process in native tissue. With these direct indices of presynaptic function, targeted at individual synapses and visualized down to their participating vesicle pools, this study should reveal important new insights into vesicle dynamics associated with presynaptic regulation and modulation.
Hadleigh Great War Centenary Project
Provide Walls of Honour for the fallen in the Town Memorial Park
Weekend D-Day celebration event 25 Jun 2004
The Gateshead branch of the Royal British Legion has been awarded a grant towards their weekend of celebrations in commemoration of the D-Day landings. This will involve a church service as well as entertainments and refreshments. The event is open to all residents in the Gateshead area.
The Legion's hall is used for a variety of clubs and individuals. As part of an ongoing refurbishment project they will extend and develop the front hall to include disabled toilets and baby-changing facilities.