Objective 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. Fields of science medical and health sciencesbasic medicinephysiologypathophysiologymedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesgeneticsRNAmedical and health scienceshealth sciencesnutritionobesity Programme(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) Topic(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2009-AdG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH EU contribution € 2 021 235,00 Address Raemistrasse 101 8092 Zuerich Switzerland See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Administrative Contact Markus Stoffel (Prof.) Principal investigator Markus Stoffel (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Switzerland EU contribution € 2 021 235,00 Address Raemistrasse 101 8092 Zuerich See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Administrative Contact Markus Stoffel (Prof.) Principal investigator Markus Stoffel (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
