Cel This proposal aims to characterize the physiology and function of the long-TRP-channel LTRPC2 (TRPC7) in both normal physiological states and during neurodegeneration induced by metabolic stress. LTRPC2 is of particular interest because recent studies have demonstrated that the channel is permeable to calcium and activated by NAD^+, enabling the channel to sense the metabolic state of the cell and implicating this channel in mechanims of cell death. We will perform detailed investigations of channel physiology using recombinant cell lines expressing the human LTRPC2 channel. Electrophysiological characterization will be undertaken to study LTRPC2 channel properties with channel activation being confirmed using single cell imaging to enable direct measurement of intracellular free calcium levels to be made. Established 'array scan' cell death assays will be utilized to investigate the effects of LTRPC2 activation and potential modulators of this activity on cell signaling endpoints including MAP kinase and transcription factor activation states. This work will provide a fundamental insight into the functions of this important yet poorly characterized channel enabling us to test a novel hypothesis of cell death mechanism. The study of these channels may reveal exciting new therapeutic opportunities for neurodegenerative diseases such as Parkinson's and Alzheimer's disease. We aim to provide an extensive practical and theoretical neuroscience-training package to the research fellow. This will be enhanced by personal development plans offering a diverse range of excellent supplementary training courses covering general computing, communication skills and drug discovery. We will provide the fellows with a unique and exciting opportunity to undertake top quality research whilst gaining a comprehensive understanding of drug discovery in a top industrial environment. Dziedzina nauki medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesbasic medicineneurologydementiaalzheimernatural scienceschemical sciencesinorganic chemistryalkaline earth metalsmedical and health sciencesbasic medicinephysiologymedical and health sciencesbasic medicineneurologyparkinson Program(-y) FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002) Temat(-y) Data not available Zaproszenie do składania wniosków Data not available System finansowania BUR - Bursaries, grants, fellowships Koordynator GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LIMITED Wkład UE Brak danych Adres Gunnels Wood Road SG1 2NY STEVENAGE Zjednoczone Królestwo Zobacz na mapie Koszt całkowity Brak danych
