Circadian rhythms in the animal intestine

旋转的地球表面受到24小时光照和黑暗的影响。在这种情况下，生物体进化出一种叫做生物钟的计时器来记录24小时的时间。生物钟几乎存在于动物身体的所有细胞中，它负责产生昼夜节律：每日睡眠/觉醒周期，进食/禁食周期，激素周期和免疫系统活动周期。生物钟被认为是根据24小时的时间来最大限度地提高动物的适应性，但它如何精确地对动物生物学做出贡献，还有许多悬而未决的问题。我们的实验室研究动物肠道的生物钟，肠道是一种经常受到消化、摄入病原体和化学物质压力的组织。在肠道中，肠道干细胞群体在整个生命过程中分裂，以取代经常因压力和损伤而丢失的细胞。我们已经证明，昼夜节律钟在肠道干细胞中的功能是以24小时为周期来计时它们的活动，并且这种时钟的破坏是有害的。这项工作是非常独特的，我们的实验室是世界上少数几个正在研究干细胞生物钟的实验室之一，我们的研究揭示了肠道中的生物计时。 该项目将建立在我们以前的NSERC项目基础上。我们将继续研究受生物钟控制的基因如何使果蝇肠道干细胞以24小时的节奏分裂。我们将确定果蝇肠道中生物钟的发育时间，并研究其在不同肠道细胞中的作用。最后，我们将探讨生物钟如何适应极端光周期的动物，北太平洋奇努克鲑鱼，那里的生物钟已经适应了恒定的光周期。 这项研究计划将开发有关地球上所有动物中存在的古老分子途径的基本知识。它将增加越来越多的工作，显示生物钟如何影响基本的组织生理学和干细胞生物学。在这一领域也有应用方面的进展。肠道时间的研究对生物工程和类器官培养物的使用具有重要意义，并将为水产养殖业和鱼类保护提供重要的见解。

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.