ENDASYM · Asymmetric endosomes in asymmetric cell division and tumorigenesis

Recent Drosophila reports show that directional Notch signalling during asymmetric cell division is mediated by asymmetric endocytic trafficking. Unpublished data from the host lab showed that directional Notch signalling is initiated by the directed targeting towards the signal-receiving cell of specific endocytic compartments, the Sara endosomes, which carry the receptor Notch and its ligand Delta. I will combine automated quantitative analysis of the movement of these endosomes with an RNAi screen to identify cytoskeletal elements controlling Sara/Notch/Delta endosome dynamics. In vitro reconstitution of endosomal trafficking and biophysical micro-manipulation of these endosomes will unravel the fine molecular role of the machineries discovered in the screen. I will then study asymmetric endosomal dynamics in the stem cells of the fly brain in wild-type and tumorigenic conditions. The ultimate goal is to uncover the relation between endosomal dynamics, stem cell self-renewal and brain tumorigenesis.