Inactivation of the Prolyl Endopeptidase-Like (PREPL) gene on chromosome 2p21 causes a recessive metabolic syndrome named Congenital Myasthenic Syndrome 22 (CMS22).
The syndrome is characterized by severe neonatal hypotonia, feeding problems and failure to thrive in early childhood followed by hyperphagia and excessive weight gain during the teenage years.
Furthermore, growth retardation is observed due to growth hormone (GH) deficiency. Prader-Willi syndrome (PWS) is caused by the lack of expression of multiple genes on the paternally inherited chromosome by imprinting defects on the chromosome 15q11-13 region, and has strikingly similar phenotypes.
This raises the possibility that overlapping pathways are affected. We have recently shown that the mitochondrial phenotype in fibroblasts derived from both PWS and CMS22 patients can be rescued by overexpressing PREPL, providing the first evidence for this hypothesis.
Specific tasks for the PhD position are:
Building on data obtained during previous PhD projects on the topic, you will use various molecular cell biological, biochemical, gene transfer, microscopical, and omics approaches in cell cultures and mouse models to identify affected pathways and substrates.
