Objetivo Maintaining oxygen homeostasis is an essential requirement for all metazoa. Oxygen is required for efficient generation of energy, however, as oxygen levels decrease (hypoxia), cells mount a variety of adaptive responses. Each cell in the body can sense and respond to hypoxia, yet the molecular mechanisms that regulate these responses are only beginning to be delineated. Hypoxia plays crucial roles in the pathophysiology of cancer, neurological dysfunction, myocardial infarction and lung disease. Therefore, the goal of the proposed research is to better understand how cells sense and adapt to hypoxia. To this end, I am using the powerful genetic model of Caenorhabditis elegans to identify novel molecular mechanisms required for oxygen homeostatic responses.A critical regulator of hypoxic responses in all cell types is the conserved hypoxia-inducible factor (HIF-1). In response to a hypoxic insult, HIF-1 transcriptionally regulates a wide variety of target genes to facilitate adaptation. Recent studies indicate that in addition to the canonical HIF-1 pathway, microRNAs (miRNAs) play important roles in hypoxic response mechanisms. miRNAs are regulatory molecules that predominantly repress protein production of their target genes, however, their roles in hypoxic adaptation are poorly understood. I recently found that specific phylogenetically conserved miRNAs are regulated by hypoxia in C. elegans; and that the function of these miRNAs is required for survival of animals in low oxygen conditions. This is truly an emerging field of science and I expect to make groundbreaking discoveries in the regulation of hypoxic and metabolic responses by miRNAs, which will improve our understanding of many disease processes.The proposed research will 1) analyze the functional roles of specific miRNAs in hypoxic responses and 2) utilize immunoprecipitation, bioinformatics and genetic screening combined with state-of-the-art deep sequencing technology to identify novel miRNA targets required for adaptation to hypoxia. Ámbito científico medical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinephysiologyhomeostasis 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-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Convocatoria de propuestas ERC-2010-StG_20091118 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida KOBENHAVNS UNIVERSITET Aportación de la UE € 1 478 508,00 Dirección NORREGADE 10 1165 Kobenhavn Dinamarca Ver en el mapa Región Danmark Hovedstaden Byen København Tipo de actividad Higher or Secondary Education Establishments Investigador principal Roger David John Pocock (Dr.) Contacto administrativo Kirsten Lange (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 KOBENHAVNS UNIVERSITET Dinamarca Aportación de la UE € 1 478 508,00 Dirección NORREGADE 10 1165 Kobenhavn Ver en el mapa Región Danmark Hovedstaden Byen København Tipo de actividad Higher or Secondary Education Establishments Investigador principal Roger David John Pocock (Dr.) Contacto administrativo Kirsten Lange (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos