Grant: Project Grant

There is a rampant increase in the incidence of inflammatory bowel diseases, like Crohn's disease, in Canada. Due to its relapsing nature, the quality of life is severely compromised for patients affected by Crohn's disease. Additionally, the estimated economic cost imposed by inflammatory bowel diseases on the Canadian healthcare system is 2.6 billion dollars per year. The exact cause of Crohn's disease remains unknown. However, it is believed to be mediated by multiple factors, including environmental and microbial factors. Our gut hosts trillions of bacteria that are beneficial to our health. During Crohn's disease, there is an enrichment of harmful microbes that can colonize the gut for years. The latter group includes certain strains of Escherichia coli that are known to mediate inflammation, and are commonly isolated from Crohn's disease patients. This group of bacteria can form protective structures that are key to their ability to persist in the human gut, known as biofilms. These are matrices of sugars and proteins that surround the bacteria and protect them from the immune system. In the work proposed here, I will use animal models and patient samples to understand how Crohn's disease-associated Escherichia coli form biofilms in the gut environment. Using microscopy and biochemistry, we will uncover the molecular mechanisms employed by bacteria to form biofilms in the intestine. Importantly, we will investigate why biofilms allow bacteria to persist in the intestine for long periods. Together, the proposed work holds great potential to further our understanding of Crohn's disease and uncover new targets for drug discovery.