Temperature and metabolic compensation mechanisms in a circadian clock system

项目总结/摘要 生物钟是细胞内的酶系统，其提供可靠的生物化学反应。 当地时间的代表性，对不同国家的健康产生深远影响 有机体与大多数酶不同，生物钟对一系列的酶不敏感。 生理温度和细胞能量水平，使生物体能够预测 黎明和黄昏可靠。生物钟的另一个标准是它们可以 通过环境线索携带，从而与本地时间保持同步。 然而，这些定义性标志的机制仍然没有完全解决， 任何生物体，因此代表了整个领域的知识差距， 生物计时因此，未来五年的总体愿景是， 在我们先前的工作，阐明温度和代谢的机制， 补偿和夹带在蓝藻的生物钟，一个系统广泛 被生物钟社区所重视。因为蛋白质及其相互作用 无论生物体如何，都是生物钟机制的基础， 作为科学界从事各种研究的重要参考点， 生物钟在过去的20年里，我们已经取得了许多有影响力的发现 蓝藻时钟的机制，并开发了创新的方法， 沿着的工具。我们的实验室最近在体外重建了完整的蓝藻时钟 使得每个组件可以在几天内被真实的实时监控， 精细和预测模型是我们假设的框架， 温度补偿、代谢补偿和夹带的机制。 因此，我们完全有能力成功地填补这些关键的知识空白。 这里所提议的工作的一个主要预期成果是详细的因果关系 将生物钟蛋白行为和相互作用与生物钟表型联系起来的模型。

Project Summary/Abstract Circadian clocks are intracellular enzymatic systems that provide a reliable biochemical representation of local time with profound consequences to health across diverse organisms. Unlike most enzymes, biological clocks are insensitive to a range of physiological temperatures and cellular energy levels so that organisms can anticipate dawn and dusk reliably. Another criterion of circadian clocks is that they can be entrained through environmental cues and thereby stay synchronized to local time. However, the mechanisms of these defining hallmarks remain incompletely resolved in any organism, and thus represent outstanding gaps in knowledge across the field of biological timekeeping. Therefore, the overall vision for the next five years is to build upon our prior work to elucidate the mechanisms of temperature and metabolic compensation and entrainment in the circadian clock of cyanobacteria, a system widely valued by the circadian clocks community. Because proteins and their interactions underpin clock mechanisms regardless of organism, lessons learned here are expected to serve as important points of reference for the scientific community working on diverse circadian clocks. Over the past 20 years, we have made many impactful discoveries on mechanism of the cyanobacterial clock and developed innovative methodologies and tools along the way. Our lab recently reconstituted the intact cyanobacterial clock in vitro such that each component can be monitored in real time over several days, and our refined and predictive model is the framework for our hypotheses regarding mechanisms of temperature compensation, metabolic compensation, and entrainment. Thus, we are very well positioned to succeed at filling these critical gaps in knowledge. A major expected outcome of the work proposed here is a detailed cause-and-effect model linking clock protein behavior and interactions to clock phenotypes in vivo.