Reference : PhD Gérard Gradwohl
Mutations in single genes can lead to rare, early-onset, forms of diabetes defined as monogenic diabetes which include Neonatal Diabetes Mellitus. These rare forms of diabetes result from mutations in genes controlling pancreatic beta cell (producing insulin) development and/or function. Recently, mutations in the winged helix transcription factor RFX6 have been identified in patients diagnosed with Mitchell-Riley syndrome characterized by neonatal diabetes and gastro-intestinal defects (Smith et al, Nature 2010).
Our Studies in mice revealed that Rfx6 is essential for islet cell maturation in the embryo (Soyer et al, Development 2010) and beta cell function in the adult (Piccand et al. Cell Reports 2014). However, the mechanisms leading to the lack of glucagon and insulin hormones in alpha and beta cell at birth, as well as to intestinal deficiencies in patients and mice lacking Rfx6 are not understood.
Therefore, the goal of this project is to decipher the pathogenesis of Mitchell-Riley syndrome by disease modeling in mice and human culture systems using engineered induced pluripotent stem cells (hiPSC) derived pancreatic islet cells and intestinal organoids.
Application Deadline : Nov. 1, 2018