Project 451312

This project will study the circadian rhythms of Inflammatory Bowel Disease (IBD). Circadian rhythms are 24 hour processes driven by the circadian clock, a conserved molecular pacemaker present in all the cells of our body. Shift work, artificial lighting, weekend schedules, and travel between time zones disrupts the circadian clock. Its impact on health is an emerging field of worldwide importance. 1 in 150 Canadians currently suffers from IBD and Colorectal Cancer is the third most common and third most fatal type of cancer. Shift-workers have increased IBD, metabolic diseases, and higher rates of colorectal cancer. We will study causal relationships between circadian dysfunction and a common feature of these illnesses: the healing of the intestinal epithelium that is maintained through resident Intestinal Stem Cells. Our CIHR-funded research showed that the intestinal epithelium exhibits circadian clock-dependent rhythms in healing, and that circadian rhythm dysfunction increases colorectal cancer. We have determined that stem cells are regulated by circadian control of signaling pathways, activated during inflammation. In this new project, we will test how the circadian clock regulates inflammation and regeneration of the colon epithelium during IBD. Using laboratory mice, we will disrupt circadian rhythms to see how healing is affected during IBD. We will see how the daily timing of food can be used as a future treatment of IBD through its effect on circadian rhythms. We will use both laboratory mice, and human biopsy samples to grow artificial intestines to discover which genes in the colon are driven by circadian rhythms. The loss of circadian rhythms worsens IBD. Our study will explain how and why this occurs, and help improve diagnostics and new timed therapies to aid in this disease.