Obiettivo 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. Campo scientifico medical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinephysiologyhomeostasis Programma(i) 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) Argomento(i) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Invito a presentare proposte ERC-2010-StG_20091118 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante KOBENHAVNS UNIVERSITET Contributo UE € 1 478 508,00 Indirizzo NORREGADE 10 1165 Kobenhavn Danimarca Mostra sulla mappa Regione Danmark Hovedstaden Byen København Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Roger David John Pocock (Dr.) Contatto amministrativo Kirsten Lange (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto KOBENHAVNS UNIVERSITET Danimarca Contributo UE € 1 478 508,00 Indirizzo NORREGADE 10 1165 Kobenhavn Mostra sulla mappa Regione Danmark Hovedstaden Byen København Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Roger David John Pocock (Dr.) Contatto amministrativo Kirsten Lange (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato