Obiettivo Small RNA-mediated regulation of gene expression is a recent addition to fundamental gene regulatory mechanisms that directly or indirectly affect possibly every gene of a eukaryotic genome. The predominant sources of small RNA in somatic tissues are microRNA genes that encode short dsRNA hairpins of evolutionary conserved sequence. Disorders of metabolism, such as obesity and type 2 diabetes are poorly understood at a molecular level. In this application we propose to explore if miRNA regulatory networks play a role in these diseases. We will employ state of the art methods for identification of small RNAs and their regulated targets and use biochemical, cell and animal model systems to study the detailed molecular mechanisms of metabolic gene regulation by miRNAs. In addition, we will investigate the underlying principles of how RNAs are taken up by cells and develop methods that will improve delivery of miRNA mimetics or inhibitors through cell-specific uptake. The specific aims of this study are: Aim 1: To define the small regulatory miRNA content of liver, muscle and adipose tissue that are associated with abnormal glucose and lipid homeostasis and to dissect the underlying molecular pathways that govern their expression. Aim 2: To characterize the functions of miRNAs in insulin resistance, glucose uptake and production, fatty acid oxidation and lipogenesis. Aim 3: To identify factors and dissect the pathways that regulate RNA uptake by cells and to develop novel pharmacological treatment strategies to manipulate miRNA-expression. Together, this proposal will shed light on the function that miRNA regulatory networks play in metabolism and in the pathophysiology of obesity/type 2 diabetes. In addition, these studies will contribute to the development of new RNA delivery technologies that are urgently needed as experimental tools as well as for novel therapeutic strategies. Campo scientifico medical and health sciencesbasic medicinephysiologypathophysiologymedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesgeneticsRNAmedical and health scienceshealth sciencesnutritionobesity 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-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Invito a presentare proposte ERC-2009-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-AG - ERC Advanced Grant Istituzione ospitante EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Contributo UE € 2 021 235,00 Indirizzo Raemistrasse 101 8092 Zuerich Svizzera Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Zürich Zürich Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Markus Stoffel (Prof.) Ricercatore principale Markus Stoffel (Prof.) 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 EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Svizzera Contributo UE € 2 021 235,00 Indirizzo Raemistrasse 101 8092 Zuerich Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Zürich Zürich Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Markus Stoffel (Prof.) Ricercatore principale Markus Stoffel (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
