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Open Access Award.
Characterisation of S. pombe Dph1 and Rhp23 and their roles in targeting polyubiquitinylated substrates to the proteasome.
The ubiquitin (Ub)-mediated protein degradation pathway regulates many critical eukaryotic cellular functions that include cell cycle control, protein quality control and transcription regulation. Four K48-linked Ub molecules attached to the target protein has been shown to be the minimal signal for degradation. Although the molecular interactions that mediate the selective recognition of Lys48… more
Closing the loop: interactive dissemination and validation of empirical medical ethics research studies.
This is an application to fund a project to run workshops, in order to disseminate and validate the results of a set of three Wellcome Trust-funded medical ethics empirical research studies. These medical ethics studies centre on the issue of competence and treatment decision-making in anorexia nervosa. This issue is important because anorexia nervosa is a mental disorder with a high morbidity an… more
Structural studies of the paxillin interaction network and its role in focal adhesion dynamics and signalling.
We propose to extend our recent structural studies (Arold et al., 2002; Hoellerer et al., 2003) to generate a dynamic picture of the interactions of the focal adhesion (FA) proteins FAK, ILK and actopaxin with the adaptor protein paxillin. We will define the role these interactions play in recruitment and activation of proteins to FAs as well as their eventual exclusion during FA disassembly. Thi… more
Active dendritic membrane properties and the of developmental regulation of synaptic circuits.
Active dendritic membrane properties and the developmental regulation of synaptic circuits The overall aim is to generate novel data on the mechanisms that regulate the development of synaptic circuits in the brain. There are two specific experimental aims: Aim (i) To investigate the contribution of active dendritic membrane properties to synapse formation and maturation. Aim (ii) To investigate the contribution of active dendritic membrane properties to the morphological growth of dendrites.
Network activity in the rodent entorhinal cortex.
1. Network activity in the rodent entorhinal cortex The entorhinal cortex (EC) and hippocampus are closely interconnected structures involved in spatial navigation and memory. The superficial layers of the EC provide the main cortical input to the hippocampus, whereas the deep layers of the EC receive the main cortical output from the hippocampus. We aim to investigate the temporal relation b… more
Investigating the role of adult neurogenesis and theglutamate transmission in the pathophysiology and treatment of depression.
Investigating the role of adult neurogenesis and glutamate transmission in the pathophysiology and treatment of depression Recent evidence suggests that a deficit in adult hippocampal neurogenesis may be critically involved in the pathophysiology of depression and that neurogenic activation may underlie the therapeutic efficacy of a number of antidepressant treatments. The aim of this project is… more
A synthetic approach to breaking the immunotolerance of HIV-1 glycans.
A synthetic approach to breaking the immunotolerance of HIV-1 glycans Despite over 20 years of concerted effort, there is no effective vaccine capable of eliciting broadly neutralising antibodies against HIV. There are two primary reasons for this. Firstly, the virally encoded proteins at the surface of the virion (gp120 and gp41) are covered with a dense layer of carbohydrates. These are create… more
VALUE IN PEOPLE AWARD.
MSc course in the Social History of Medicine.
The role of cardiac stem cells in response to cardiac injury.
While the response to imposed cardiac stresses (e.g. afterload due to hypertension) have traditionally been understood in terms of the manifest morphological changes (e.g. hypertrophy and dilatation), the molecular determinants of these distinct morphological states are increasingly well understood the molecular level. Genomic analyses have yielded a number of potential key nodes that may determ… more
Art & Biomedical Science: A Biannual Artist's Residency.
Art and Biomedical Science: a biannual artist's residency and related exhibition and lecture series This is an application for funding to initiate a biannual artist's residency and related exhibition and lecture series, co-hosted by the Ruskin School of Drawing and Fine Art, University of Oxford and the University's Department of Physiology, Anatomy and Genetics. Through their own research and … more
Regulating international biobank networks.
The purpose of this research is to identify, evaluate and recommend appropriate regulatory solutions to the current legal obstacles which inhibit the sharing of biological samples and digital information in biobanks used for genomic research within Europe and at a global level. It will generate recommendations for policy-makers about the best options for the future regulation of biobanks. Thi… more
Connecting transcription of small nuclear RNA genes with RNA 3 end formation .
The 3 ends of human small nuclear (sn)RNAs synthesized by RNA polymerase II (pol II) are formed by RNA processing directed by the snRNA gene-specific 3 box. In living cells (in vivo), processing occurs efficiently only when transcription is initiated from an snRNA promoter. Our findings indicate that termination of transcription, in turn, requires recognition of the 3 box. However, the molecular … more
Comparative genomics on the vertebrate ParaHox gene cluster.
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, butin 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… more
The role of nicotinamide nucleotide hydrogenase in beta-cell metabolism, detoxification of reactive oxygen species and insulin secretion.
Our recent studies have identified a novel protein that is implicated in both insulin secretion and free radical detoxification: nicotinamide nucleotide transhydrogenase (Nnt). Mice lacking functional Nnt are glucose intolerant due to impaired insulin secretion. This is associated with a glucose-dependent increase in reactive oxygen species (ROS) in pancreatic beta-cells and lower ATP production.… more
Sub-second dopamine release during cost-benefit decision making.
The mesocorticolimbic dopamine system has been central to many accounts of outcome processing and response allocation. Its dysfunction is also implicated in numerous neuropsychiatric disorders from schizophrenia to addiction. To date, however, it remains unknown what precise role dopamine plays in directing optimal decision-making and what the temporal dynamics of its involvement are. To investig… more
Etiology of acute respiratory infection and shedding of influenza virus among Kenyan children.
Acute respiratory infection (ARI) is a leading cause of death among children in sub-Saharan Africa. Recent studies suggest that viruses make an important contribution to the burden of disease. Nevertheless, the precise contribution of viruses, including influenza, parainfluenzae, adenovirus, respiratory syncytial virus, human metapneumovirus and cytomegalovirus has not been quantified in tropical… more
Efficient 3'-end processing of intron-free G-protein coupled receptor genes.
The open reading frames of most eukaryotic protein encoding genes are interrupted by non-coding sequences. In order to produce a contiguous uninterrupted and translatable messenger RNA, these intervening sequences have to be precisely excised by the splicing apparatus. In recent years, it became evident that the removal of these introns not only results in an mRNA with an uninterrupted ORF but it… more
Role of the IL-23/IL-17 axis in Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC). Experimental and clinical studies suggest that IL-12 plays a role in CD via promotion of Th1 cells and increased IFN-g and TNF-a. IL-23 is a novel member of the IL-12 cytokine family. While IL-12 drives the classical Th1 response, IL-23 … more