PhD in cellular and molecular biology

The Humbert's team offers a 3 years position for a PhD candidate.

NSCs in the adult Rodent subventricular zone (SVZ) generate neurons throughout life. Neurogenesis persists in the adult Human brain with new interneurons, probably born in the nearby SVZ, adding to the striatum. Interestingly, striatal neurogenesis decreases in Huntington’s disease (HD) patients. HD is a fatal neurodegenerative disorder with an adult onset. An autosomal dominant mutation of the huntingtin gene (Hdh) is responsible for the symptoms. The mutation is an abnormal expansion of a polymorphic CAG repeat present on the exon 1 sequence of the gene leading to an abnormal polyglutamine stretch at the N-terminus of the huntingtin protein (HTT) that is toxic for cortical and striatal neurons. We hypothesize that mutant HTT (mHTT) decreases neurogenesis in the SVZ by accelerating aging in NSCs. There is evidence of accelerated aging in HD with decreased neurogenesis in HD mouse models. We propose to test our hypothesis using SVZ cells cultures and adult SVZ whole-mounts from murine models of HD. Understanding the regulation of NSCs in the SVZ will help to design new therapies to sustain neurogenesis in the old and diseased brain.