Objetivo Cardiac muscle death, unmatched by muscle cell creation, is the hallmark of acute myocardial infarction and chronic cardiomyopathies. The notion of heart failure as a muscle-cell deficiency disease has driven interest worldwide in ways to increase heart muscle cell number, by over-riding cell cycle constraints, suppressing cell death, or, most directly, cell grafting. Using stem cell antigen-1, we previously identified telomerase-expressing cells in adult mouse myocardium, which have salutary properties for bona fide cardiac regeneration. Here, we seek to address systematically the mechanisms for long-term self-renewal in Sca-1+ adult cardiac progenitor cells and in the smaller side population fraction, which is clonogenic and expresses telomerase at even higher levels. Specifically, we propose to study the roles of telomerase and of the telomere-capping protein, TRF2. Aim 1, Determine the properties of adult cardiac progenitor cells in mice that lack the RNA component of telomerase (TERC). Aim 2, Determine the properties of adult cardiac progenitor cells in mice that lack the catalytic component (TERT). To distinguish between effects of these two gene products themselves versus those that depend on cumulative telomere dysfunction, G2- and G5-null mice will be compared. Aim 3, Determine the properties of adult cardiac muscle and adult cardiac progenitor cells that lack the telomere-capping protein TRF2. Aim 4, Test the prediction that forced expression of TERT and TRF2 can augment cardiac muscle engraftment in vivo and enhance the clonal derivation of adult cardiac progenitor cells in vitro, without adversely affecting the cells differentiation potential. Work proposed in Aims 1-3 would provide indispensable fundamental information about the function of endogenous telomerase in adult cardiac progenitor cells. Conversely, work in Aim 4 would test potential therapeutic implications of telomerase and a telomere-capping protein with this auspicious population. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesclinical medicinecardiology Palabras clave cardiac heart heart failure myocardial infarction myocardium regeneration side population stem cell antigen-1 telomerase Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Convocatoria de propuestas ERC-2008-AdG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Aportación de la UE € 2 497 576,00 Dirección SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Reino Unido Ver en el mapa Región London Inner London — West Westminster Tipo de actividad Higher or Secondary Education Establishments Investigador principal Michael David Schneider (Prof.) Contacto administrativo Tatjana Palalic (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Reino Unido Aportación de la UE € 2 497 576,00 Dirección SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Ver en el mapa Región London Inner London — West Westminster Tipo de actividad Higher or Secondary Education Establishments Investigador principal Michael David Schneider (Prof.) Contacto administrativo Tatjana Palalic (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
