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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 Men’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 £10,000 to make improvements to their venue so that it can be used for more classes and activities.

Grant to Royal British Legion Tipton Branch 19 May 2016

Remembering Tipton's World War One Heroes

Grant awarded to The Royal British Legion (Forest Hall) Branch And Club (Tyne & Wear) 20 Nov 1998

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.

Mechanisms of client protein activation and regulation by the Hsp90 molecular chaperone system. 10 May 2011

The Hsp90 molecular chaperone plays an essential role in the stabilisation andactivation of a wide range of client' proteins, including some of the most important proteins required for cell maintenance and regulation in eukaryotic organisms from yeast to humans. Hsp90 itself is regulated by a plethora of co-chaperone proteins that modulate its essential ATPase coupled conformational cycle, and/or act as adaptors facilitating recruitment of specific client proteins to the Hsp90 machinery. Involvement of Hsp90-dependent clients in the development and progression of cancer, has led to enormous interest in Hsp90 as a drug target, and an emerging realisation of Hsp90 involvement in viral and and parasitic infections, suggests that Hsp90 is important in many other diseases. Although much of the biochemistry of the Hsp90 system has been unravelled in recent years, central questions of Hsp90 biology remain unanswered. To address this, we propose to define at the structural level the molecular mechanisms by which the Hsp90 molecular chaperone system contributes to the activation, stabilization and regulation of its selected client' proteins in eukaryotic cells

Amount: £2,804,975
Funder: The Wellcome Trust
Recipient: University of Sussex

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

Roles of the supporting cells in the mechanical responses and neural excitation in the mammalian cochlea. 27 May 2009

Pillar and Deiters cells have conspicuous arrangements of parallel microtubules and microfilaments spanning the cell bodies and bundled up by cross-linking proteins. These cells differ from the hair cells, in that they extend from the reticular lamina to the basilar membrane, the vibrations of which determine the excitation of the mechano-sensitive hair cells. The rigidity of the reticular lamina depends on the apical junctions between the pillar, Deiters cells and the hair cells, and the cytosk eletal arrangements at their apices. Besides, pillar and Deiters cell bases sit on the basilar membrane and they should, therefore, contribute to its stiffness and help direct the amplifying forces generated by the motile outer hair cells. In this project I aim to examine the roles of the apical junction complexes and the microtubule bundles of pillar and Deiters cells in cochlear mechanical responses and neural excitation. To accomplish these aims I propose to: 1) generate mouse lines in which structural proteins are specifically deleted in the pillar and Deiters cells, 2) determine the effects of those changes on cochlear structure and development and 3) determine the effects of these genetic manipulations on cochlear mechanical and neural responses in vivo.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Sussex

Impact of DNA non homologous end joining on stem cell function in vivo. 30 Apr 2008

DNA double strand breaks (DSBs) arise from oxidative damage and following radiation treatment. Their impact on development and particularly on stem cells is unclear but is topical and important. As a result of basic research, an exquisitely sensitive technique to monitor DSB repair in vivo has been recently developed. Additionally, we recently characterised a mouse mutated in DNA ligase IV (LigIVY288C), a component of DNA non-homologous end-joining (NHEJ), the major DSB repair pathway. We showed that haematopoietic stem cell (HSC) numbers and function are diminished in LigIVY288C mice demonstrating that unrepaired DSBs impact on stem cells. Here, we will pursue our analysis by monitoring radiation-induced DSB repair in three stem cell compartments, the HSCs, the ventricular and sub-ventricular zone of the developing embryonic brain, and the intestinal crypt. For this we will use normal mice. We will also exploit LigIVY288C mice to examine the impact of impaired NHEJ in the embryonic br ain and intestinal crypt, where stem cells can be readily identified. Our major focus will be on embryonic neuronal development since microcephaly is a feature of LIG4 syndrome, a disorder caused by mutations in LigIV, and since our preliminary studies have shown abnormalities in the LigIVY288C embryonic brain.

Amount: £246,628
Funder: The Wellcome Trust
Recipient: University of Sussex

Student Elective Prize for Mr Christopher Ball 29 Aug 2008

A retrospective study into the management of Cervical Spine injuries over a 12 month period, with specific interest into the adherence to the Canadian CT Cervical Spine Rule over the NEXUS rule

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

Student Elective Prize for Mr Ian Densham 29 Aug 2008

'Maternal Outcome of Anaesthesia for Caesarean Delivery in an Ethiopia tertiary Referral Centre: A Retrospective Observational Study'

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

Student Elective Prize for Ms Stefanie Binzer 29 Aug 2008

The genetic component associated with the high incidence of Multiple Sclerosis in a family from the Faeroe Islands.

Amount: £1,300
Funder: The Wellcome Trust
Recipient: University of Sussex

Core costs 18 Jan 2019

To support the work of the charity r.

Amount: £1,000
Funder: County Durham Community Foundation
Recipient: Royal British Legion

The genetic basis of podoconiosis - a model for gene environment interactions. 09 May 2006

Podoconiosis (endemic non-filarial elephantiasis) is a common geochemical disease resulting in severe lower limb deformity, debilitation and economic loss for affected families. Our studies to date provide convincing evidence that the disease results from the interaction between a host gene (or possibly genes) and an environmental factor, probably silica, found in the red clay soils to which susceptible individuals are exposed. The aim of this study is to identify the gene(s) responsible for this condition using a robust affected sibling pair genetic linkage study design. The high familial aggregation of cases, the distinctive phenotype and lack of phenocopies, coupled with the evidence for a single major gene mode of inheritance in this population significantly enhance the likelihood of successful outcome. Identification of the gene(s) involved will lead to better understanding of the pathogenesis of this condition including mechanisms of fibrosis that are common to other disorders such as filiarial elephantiasis and causes of pulmonary fibrosis, including silicosis. Elucidation of the molecular mechanisms involved in podoconiosis could also broaden our understanding of gene-environment interactions in the development of complex disorders more generally where the genetic and environmental factors are less clearly defined.

Amount: £280,187
Funder: The Wellcome Trust
Recipient: University of Sussex

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

RBL Portstewart Branching Out 26 Apr 2018

The group, based in Portstewart, are using a grant of £6,500 to replace their hall’s heating system and improve its insulation, making it more usable for community events.

Grant to Royal British Legion, Greenhithe & Swanscombe 23 May 2014

The impact of WW1 on Dartford and its residents