Grant: Project Grant

The digestive system is complex, and it interacts directly with a large number of microbes. Consequently, small problems can lead to various types of digestive diseases. Crohn's disease and ulcerative colitis, collectively named inflammatory bowel diseases (IBD) affect 1 in 150 Canadians. Although these two diseases are etiologically different, they both are linked to a cellular mechanism called autophagy. Autophagy is the process by which cells degrade and recycle their own constituents. Autophagy can thus be compared to a recycling factory, where non-essential or damaged constituents can be destroyed and reused for other purposes. Autophagy is induced by different signals. In the intestine, autophagy (the recycling factory) also helps to destroy bad microbes and help to maintain the good ones. In an effort to understand how differences in our genes predispose individuals to develop IBD, differences in genes of affected and unaffected individuals were compared to identify mutations linked to an increasing susceptibility to develop IBD. These approaches have identified a large number of genes linked to IBD, and importantly a good proportion of those genes are regulators of autophagy. However, due to the lack of affordable and time-efficient systems to study the role of these genes in digestive health, their roles in the development or progression of IBD are for the most part unexplored. In this proposal, we will characterize, using Drosophila melanogaster (fruit flies) as an innovative in vivo model of gut health, the role of autophagy on gut function and gut/microbes interaction. Moreover, we will also quantify using a powerful new approach how autophagy is regulated in vivo under stress, and finally we will identify novel potential targets that could eventually help IBD patients with impaired autophagy. The identification of new regulators of intestinal health will generate new basic and translational research avenues and identify new targets for therapies.