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Results

The future of A level science - a series of stakeholder conferences aimed at informing practice and policy. 30 Aug 2006

We intend to set up a programme of stakeholder conferences to inform the new Physics, Chemistry, Biology and Psychology A level courses due to be introduced in 2008. The National Science Learning Centre will host four events leading to the publication of a report informing practice and policy, and implementation of the new courses. We anticipate that 240 key education, science and other stakeholders will be involved in the programme directly, and that the outcomes and outputs will affect many thousands over the subsequent years. This systematic approach is long overdue and would help to ensure that the content and approach at A Level better meets the needs of science, the FE and schools sector, young people and industry. The Qualifications and Curriculum Authority has expressed enthusiastic interest in this model and were it to be successful, we would expect it to be adopted more widely as mechanism for informing curriculum development in science and beyond. The Stakeholder Conference Programme will achieve the following objectives: To identify priorities, themes, core issues and contexts for each of the four science A levels, amongst each of the stakeholder groups; To develop a methodology to inform curriculum development that could be replicated and extended; To act as a forum where research scientists can work with science educationalists to illustrate curriculum content with contemporary examples; To professionalise and make more transparent the curriculum development process. Main audience: 1. Conference attendees and the organisations they represent. 2. Post-16 lecturers and teachers. 3. Policymakers.

Amount: £30,000
Funder: The Wellcome Trust
Recipient: University of York

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.

Amount: £254,448
Funder: The Wellcome Trust
Recipient: University of Sussex

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

Amount: £231,619
Funder: The Wellcome Trust
Recipient: University of Sussex

Molecular mechanism of bacteriocin import into bacterial cells. 16 May 2007

Our proposal brings together expertise in biochemistry/structural biology (York), microbiology (Nottingham) and spectroscopy (Norwich) to determine how nuclease colicins penetrate the cell defences of bacteria. The programme has four key goals: (1) To establish the mechanism by which nuclease colicins translocate acrossthe E. coli outer membrane, centred on a structural dissection of the multiprotein, membrane-bound complex that assembles prior to import. (2) To determine the function of the periplasmic Tol-Pal complex in conjunction with how and why it is parasitised by translocating colicins, using microscopy to determine whether colicins target the bacterial septation machinery, biochemical analysis of the overexpressed membrane-bound TolQRA complex, along with functional dissection of TolB through spectroscopic and biophysical analysis. (3) To establish the mechanism by which colicin nucleases retro-translocate across the bacterial inner membrane using a range of mutants, cell-based assays and crosslinking that will probe the role of electrostatics and the AAA+ATPase FtsH in membrane trafficking. (4) To use NMR to define the conformational ensemble of the natively disordered N-terminal domains of Ton- and Tol-dependent colicins that recruit protein partners for import and examine TolB binding mechanism using pre-steady state methods.

Amount: £350,713
Funder: The Wellcome Trust
Recipient: University of York

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.

Amount: £126,654
Funder: The Wellcome Trust
Recipient: University of Sussex

Comparative genomics of the vertebrate ParaHox gene cluster. 01 Nov 2006

The clustered Hox genes comprise only 39 of the >200 homeobox genes in the human genome. The non-Hox homeobox genes are usually studied in isolation, but in fact some are in gene clusters. We found that three (Gsx, Xlox/Pdx, Cdx) form the ParaHox cluster in amphioxus, human, mouse, Xenopus and basal ray-finned fish, but not in zebrafish and pufferfish (where the constituent genes have dispersed). We will use a combination of comparative genomics and experimental assays to ask: (1) How conserved is the ParaHox gene cluster? To test, we will analyse two species chosen for their positions in vertebrate diversity. (2) When, how and why did the ParaHox cluster disintegrate in teleost fish evolution? We hypothesize that whole genome duplication (WGD) at the base of the teleosts allowed interdigitated ParaHox genes to be dissociated. We will test by comparison between fish branching before and after the WGD, including zebrafish and some non-traditional models. (3) What is the functional reason for the cluster? We hypothesize the genes are trapped by shared enhancers and overlapping gene organisation; we will test this by determining the activity of conserved non-coding regions using Xenopus transgenics. (4) What are the implications for zebrafish as a model?

Amount: £18,349
Funder: The Wellcome Trust
Recipient: University of York

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

Amount: £1,600,995
Funder: The Wellcome Trust
Recipient: University of Sussex

Biomedical vacation scholarship. 29 May 2009

Not available

Amount: £3,960
Funder: The Wellcome Trust
Recipient: University of York

Open Access Awards. 16 Sep 2008

Not available

Amount: £20,000
Funder: The Wellcome Trust
Recipient: University of York

Regiospecific glycosylation of immune potentiators: a novel platform for modifying adjuvant activity. 01 Jul 2008

Adjuvants represent blunt tools to manipulate immunogenicity, with few molecular approaches available to selectively tune activity profiles. We have developed a unique biocatalysis system, based on glycosyltransferases from arabidopsis, that can regioselectively glycosylate small molecule immune potentiators. We have shown that for two polyphenols, regiospecific glucosylation alters bioactivity on dendritic cells (measured by differential regulation of CD40, CD80 and IL-6). We propose to exte nd these observations, using scalable in vitro assays to measure additional parameters of dendritic cell activation (including high content screening of cytoskeletal morphology), and adoptive transfer and immunization experiments. These studies will provide data to validate the concept that regiospecific glycosylation can optimize the functionality of small molecule immune potentiators. Over two-years, we will synthesize 20 regioselective mono- and di-glycosides based on 4 scaffolds. For each new glycoside, we will be able to interrogate an expanding database and determine whether our assays, alone or in combination, constitute a predictive algorithm for in vivo activity and the effects of glycosylation. This Project will provide the foundation for evaluating a broader range of scaffolds and an extended platform of GTs, as well as a basis for future studies on the mechanism(s) underlying these regioselective effects on scaffold activity.

Amount: £219,242
Funder: The Wellcome Trust
Recipient: University of York

Investigating the dynamics of vesicle pool traffic in hippocampal synapses. 11 Feb 2008

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.

Amount: £271,228
Funder: The Wellcome Trust
Recipient: University of Sussex

The Loop - Living Well 07 Jun 2018

To help 50 people improve their mental and physical wellbeing by undertaking various activities.

Amount: £2,000
Funder: Suffolk Community Foundation
Recipient: Volunteering Matters

The Loop - Living Well 06 Jun 2018

To help 50 people improve their mental and physical wellbeing by undertaking various activities.

Amount: £2,500
Funder: Suffolk Community Foundation
Recipient: Volunteering Matters

Grant to Volunteering Matters 20 Dec 2013

Great War pop-up exhibition

Amount: £9,700
Funder: The National Lottery Heritage Fund
Recipient: Volunteering Matters
Region: North East
District: County Durham

Grant to Royal British Legion Camelford 07 May 2014

Camelford and Advent during the First World War

Grant to Royal British Legion 19 Sep 2013

Events to commemorate the Centenary of the First World War in 2014

Grant to Royal British Legion Newbiggin & North Seaton Branch 27 Aug 2014

Provide Walls of Honour for the fallen in the Town Memorial Park

Grant to Volunteering Matters 25 Jul 2016

Visions of volunteering (then and now )

Amount: £9,600
Funder: The National Lottery Heritage Fund
Recipient: Volunteering Matters
Region: North East
District: County Durham