Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Extracellular vesicles (EVs) are microscopic particles released by all cell types. Intriguingly, they have the capacity to carry and protect specific molecular cargos (ie. RNA and proteins) outside of the cell. In animals, EVs can be carried through biological fluids, dock to distant cells of the organism and release their molecular cargos within the recipient cell. Importantly, solid tumors release a very high number of EVs, which play crucial roles in cancer formation and progression. Therefore, I hypothesize that the trafficking of molecular cargos to EVs involves transport pathways conserved through evolution and that these pathways contribute to cancer progression. In order to test these hypotheses, I rely on a large panel of cell lines derived from human tumors and fruit fly embryos as well as a mice model. Upon purification of EVs from cultured cell environment, preparations undergo extensive validation, based on electronic microscopy and protein identification. Next, I use the cutting-edge technologies of next-generation sequencing and mass spectrometry, which respectively allow identification of all EVs RNA and protein cargos. Upon bioinformatic analysis of these datasets, I will identify the molecular determinants of cargo targeting to EVs. These observations will then be confirmed in cells by transgenic removal of these molecular determinants and assessment of resulting changes in EVs cargos. Furthermore, I will use a mice model to extend my observations to living animals. In that respect, non-invasive cells, either exposed to tumor-shed EVs, exposed to transgenic tumor-shed EVs or left untreated will be injected in mice. Tumor formation and progression in these animals will then be monitored. My study will decipher the molecular determinants of EVs cargo assembly and shed light on its evolutionary conservation. Moreover, it will define its roles in cancer progression and identify promising drug targets for future cancer therapies.