Circadian rhythms in the animal intestine

点击翻译按钮获取中文摘要

The surface of the rotating Earth is subject to a 24 hour photoperiod of light and darkness. In these conditions, living organisms have evolved a timekeeper called the circadian clock to keep track of 24 hour time. The clock is present in nearly all the cells of the animal body, where it is responsible for producing circadian rhythms: daily sleep/wake cycles, feeding/fasting cycles, hormone cycles, and cycles in immune system activity. The circadian clock is thought to maximize animal fitness according to 24 hour time, yet there are many outstanding questions of how it precisely contributes to animal biology. Our lab studies the circadian clock in the animal intestine, a tissue subject to frequent stresses from digestion, ingested pathogens, and chemicals. In the intestine a population of intestinal stem cells divides throughout life to replace cells that are often lost to stress and injury. We have shown that the circadian clock functions in intestinal stem cells to time their activity with 24 hour cycles, and that disruption of this clock is detrimental. This work is quite unique, our lab is among a handful worldwide that is studying the circadian clock in stem cells, and our research sheds light biological timing in the intestine. This proposal will build on our previous NSERC project. We will continue our work studying how genes, that are controlled by the circadian clock, cause Drosophila intestinal stem cells to divide with a 24 hour rhythm. We will determine when the circadian clock develops in the Drosophila intestine, and study its role in the different intestinal cells present. We will finally explore how the circadian clock has adapted to function in animals that are subject to extreme photoperiod, North Pacific Chinook salmon, where the circadian clock has adapted to periods of constant light. This research program will develop basic knowledge about an ancient molecular pathway that is present in all animals on Earth. It will add to a growing body of work that shows how the circadian clock affects fundamental tissue physiology and stem cell biology. There are applied advances in this area as well. The study of intestinal timing is of great importance to bioengineering and the use of organoid cultures, and will provide critical insight for the aquaculture industry and fish conservation.