Objective Normal physiology depends on defined functional output of differentiated cells. A century of Developmental–Biology studies revealed diverse mechanisms for differentiation, however once ‘terminally’ differentiated, cells are thought to naïvely stay put. However differentiated cells are surprisingly fragile, for example, phenotypic collapse and de–differentiation of β–cells was recently discovered in pathogenesis of type 2 diabetes. These discoveries necessitate investigations of key questions: How is cell–type identity robustly maintained for decades in the adult organism? What are the genetic mechanisms for continuous maintenance of differentiation and identity? microRNAs, are known to impart robustness to differentiation. Do they play important roles in maintenance of adult β–cell identity?Our overarching objective is to explore the exciting hypotheses that(i) Networks of microRNA and protein–coding genes are required to maintain adult cell identity.(ii) microRNAs confer robustness to adult β–cell identity by repressing disallowed genes that are deleterious to β–cells.(iii) Dysregulated microRNA disrupt cell identity and is a likely vector of pathology.Our planned research has the potential of producing conceptual breakthroughs including:(1) Revolutionary view of microRNAs as agents of adult cell identity and discoveries of specific microRNAs that are crucial for maintaining β–cell identity(2) Experimental discovery of targets and networks involved in adult β–cell de-differentiation.(3) In–vivo evidence for combinatorial action of multiple microRNAs in control of β–cell identity.(4) Uncovering new links from de–differentiation and into metabolic diseases that may drive future medical innovation through usage of small RNAs to reinforce β–cell differentiation. Fields of science natural sciencesbiological sciencesdevelopmental biologymedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologynatural sciencesbiological sciencesgeneticsRNA 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-CG-2013-LS4 - ERC Consolidator Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2013-CoG See other projects for this call Funding Scheme ERC-CG - ERC Consolidator Grants Host institution WEIZMANN INSTITUTE OF SCIENCE EU contribution € 2 000 000,00 Address HERZL STREET 234 7610001 Rehovot Israel See on map Activity type Higher or Secondary Education Establishments Principal investigator Eran Hornstein (Dr.) Administrative Contact Gabi Bernstein (Ms.) 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 WEIZMANN INSTITUTE OF SCIENCE Israel EU contribution € 2 000 000,00 Address HERZL STREET 234 7610001 Rehovot See on map Activity type Higher or Secondary Education Establishments Principal investigator Eran Hornstein (Dr.) Administrative Contact Gabi Bernstein (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data