MIRNABETAIDENTITY · microRNAs confer robustness to adult beta–cell identity

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.