Endosomal regulation of autophagy
Early endosomes represent important sorting stations of internalized material. Misrouting of multiple cargos are associated with a large array of diseases. This project focuses on understanding molecularly how RAB21 and its GEF MTMR13 regulate the endolysosomal sorting of VAMP8, a SNARE protein required for autophagosome-lysosome fusion. We want to identify what regulates MTMR13 activation upon starvation, what machinery is governed by RAB21 to mediate VAMP8 sorting and what are the implications of VAMP8 mis-sorting in colorectal cancer. We use imaging, biochemistry, proteomic and genetic approaches to answer these questions and we perform experiments in mammalian cell culture models and Drosophila.
Regulation of RAB GTPases upon various stimuli
RAB GTPases govern trafficking events. They are under the dynamic regulation of GEFs and GAPs, which shape their membrane recruitment. Single RABs can be activated by various stimuli and regulate trafficking differently. However, how RAB GTPases integrate these various stimuli to generate a different response is not well understood. We use proximity-ligation techniques coupled to genetic approaches to molecularly understand these regulatory events.
Impact of autophagy on intestinal homeostasis
Autophagy dysfunctions have been implicated in inflammatory bowel diseases (IBD). GWAS studies have identified numerous variants in membrane trafficking or autophagic regulators. How are genetic predispositions inter-twinned with environmental factors, the microbiota and innate immune responses is still poorly understood. Using Drosophila as a simple genetic model and human enteroids to understand how autophagy impairment affects intestinal homeostasis, we hope to be able to better define the importance of genetic factors in IBD.