Circadian rhythms in the animal intestine

动物肠道的昼夜节律

• 批准号: RGPIN-2020-04252
• 负责人: Karpowicz, Phillip
• 金额: $ 3.64万
• 依托单位: University of Windsor
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744770
• 关键词: Circadian; rhythms; animal; intestine

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.

自转地球的表面受到24小时光周期的影响。在这种情况下，生物进化出一种名为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体内的所有细胞中，负责产生昼夜节律：每日睡眠/清醒周期、进食/禁食周期、激素周期和免疫系统活动周期。生物钟被认为可以根据24小时的时间最大化动物的健康，但关于它如何准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，这是一种经常受到消化、摄入的病原体和化学物质影响的组织。在肠道中，一群肠道干细胞在一生中分裂，以取代经常因应激和损伤而丢失的细胞。我们已经证明，肠道干细胞的生物钟功能是以24小时为周期来计时它们的活动，而破坏这一时钟是有害的。这项工作相当独特，我们的实验室是世界上少数几个研究干细胞生物钟的实验室之一，我们的研究揭示了肠道的生物计时。这项建议将建立在我们之前的NSERC项目的基础上。我们将继续研究由生物钟控制的基因如何导致果蝇肠道干细胞以24小时的节奏分裂。我们将确定生物钟在果蝇肠道中发育的时间，并研究其在不同肠道细胞中的作用。我们最后将探索生物钟是如何适应极端光周期的动物的功能的，北太平洋奇努克鲑鱼，在那里生物钟已经适应了持续的光周期。这项研究计划将发展关于地球上所有动物都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，展示生物钟如何影响基础组织生理学和干细胞生物学。在这一领域也有应用上的进展。肠道时机的研究对生物工程和有机养殖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。