Exploring Circadian Cycles in Intestinal Firmicutes

地球上的大多数生命都遵循可预测的环境周期（光明和黑暗，温度变化等）指导的日常生活。日常生活的一些方面是由外部线索控制的，而另一些则是通过昼夜节律来维持的。这些内部的、自我维持的时钟周期约为24小时，使微生物、动物和植物能够预测和准备每天的波动。最近，由一种或几种蛋白质组成的自我调节时钟被发现，这表明一个强健的时钟的基因很容易获得。到目前为止，真正的细菌时钟只在光养菌（从阳光中获取能量）中被表征，但其他细菌可能会从内部时钟中受益。特别是肠道微生物，它们有一个时钟，可以让它们预测宿主活动的变化，比没有时钟的细菌更有优势。轮班工人经常会出现肠道不适和体重增加。与人类宿主不同步的肠道微生物可能会导致这些不必要的生理变化。揭示肠道微生物的生物钟将为有针对性的补救措施提供信息，以对抗伴随我们现代生活方式而来的不良生理变化。迄今为止，肠道微生物群落的复杂性和缺乏任何日常过程的读数阻碍了观察大多数肠道微生物正常功能的能力。为了避免这些问题，野生刺尾鱼及其肠道细菌将被用作描述日常代谢和发育周期的自然模型系统。厚壁菌门的一组，Epulopiscium spp.和相关的epulos，是天然存在的，丰富的肠道共生体，在一个可预测的过程中，每24小时产生一次明显的内部后代。这为自然共生种群的日常生理变化提供了一个尺度。肠道生态系统的日常物理化学变化将被表征，以揭示可能用于夹带的规律波动。共生振荡将通过分析它们的时间转录组和广泛分布的时钟蛋白的周期性氧化还原循环来确定。本项目为博士后、研究生和本科生科研人员提供培训机会。将制定一项本科生互惠交流计划，以建立一个合作学习小组，为研究项目做出贡献，同时为高级培训建立网络和技能。土著太平洋岛民和其他在科学领域代表性不足的群体将专门为这些机会招聘。项目结果将揭示肠道共生体与宿主协调活动的基本模式。

Most life on Earth follows a daily routine guided by predictable environmental cycles (light and dark, temperature changes etc.). Some aspects of the routine are controlled by external cues while some are maintained using circadian rhythms. These internal, self-sustained clocks with a periodicity of about 24 hours allow microbes, animals and plants to anticipate and prepare for daily fluctuations. Recently, self-regulated clocks composed of one or a few proteins have been discovered, suggesting that genes for a robust clock can be readily acquired. Thus far, true bacterial clockworks have been characterized only in phototrophs (that harvest energy from sunlight), but other bacteria would likely benefit from an internal clock. Specifically gut microbes, with a clock that allows them to anticipate changes in host activities, would have an advantage over bacteria without a clock. Shift workers often suffer intestinal discomfort and weight gain. Gut microbes out of sync with their human host may be contributing to these unwanted physiological changes. Uncovering a gut microbe circadian clock would inform targeted remedies to combat undesirable physiological changes that accompany our modern lifestyles.To date, the complexity of gut microbial communities and lack of any readout for daily processes have hampered the ability to observe regular functions in most gut microbes. To circumvent these issues, wild surgeonfish and their intestinal bacteria will be used as a natural model system to describe daily metabolic and developmental cycles. One group of Firmicutes, Epulopiscium spp. and related epulos, are naturally occurring, abundant intestinal symbionts that produce conspicuous internal offspring once every 24 hours in a predictable process. This provides a meter of everyday physiological changes in natural symbiont populations. Daily physicochemical changes in the intestinal ecosystem will be characterized to uncover regular fluctuations that may be used for entrainment. Symbiont oscillations will be determined by analyses of their temporal transcriptome and the cyclical redox cycle of a widely distributed clock protein. The project provides training opportunities for postdoctoral, graduate and undergraduate researchers. An undergraduate Reciprocal Exchange Program will be developed to build a cooperative learning group that will contribute to the research project while building networks and skills for advanced training. Native Pacific Islanders and other groups that are underrepresented in the sciences will be specifically recruited for these opportunities. Project results will uncover fundamental modes by which gut symbionts coordinate their activities with those of their host.