Temperature and metabolic compensation mechanisms in a circadian clock system

生物钟系统中的温度和代谢补偿机制

• 批准号: 10797991
• 负责人: Andy LiWang
• 金额: $ 7.38万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797991
• 关键词: Administrative Supplement; Behavior; Biochemical; Biological; Biological Clocks; Clock protein; Communities; Compensation; Cues; Cyanobacterium; Enzymes; Health; In Vitro; Knowledge; Learning; Link; Measurement; Measures; Metabolic; Methodology; Modeling; Molecular Weight; Monitor; Organism; Outcome; Phenotype; Physiological; Positioning Attribute; Proteins; Radial; Sampling; System; Temperature; Time; Vision; Work; circadian pacemaker; in vivo; innovation; instrument; light scattering; predictive modeling; reconstitution; tool

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.

项目概要/摘要 昼夜节律钟是细胞内酶系统，提供可靠的生化 当地时间的表示对不同群体的健康产生深远影响 有机体。与大多数酶不同，生物钟对一系列因素不敏感 生理温度和细胞能量水平，以便生物体可以预测 黎明和黄昏可靠。生物钟的另一个标准是它们可以 通过环境线索夹带，从而与当地时间保持同步。 然而，这些定义标志的机制仍未完全解决 任何有机体，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打造 基于我们之前阐明温度和代谢机制的工作 蓝藻生物钟的补偿和夹带，这是一个广泛应用的系统 受到生物钟界的重视。因为蛋白质及其相互作用 无论生物体如何，都支持时钟机制，期望在这里吸取教训 为科学界致力于不同领域的研究提供重要参考 生物钟。在过去的20年里，我们在以下方面取得了许多有影响的发现： 蓝藻时钟的机制并开发了创新方法和 沿途的工具。我们的实验室最近在体外重建了完整的蓝藻时钟 这样每个组件都可以在几天内实时监控，并且我们的 完善的预测模型是我们关于以下方面的假设的框架 温度补偿、代谢补偿和夹带机制。 因此，我们完全有能力成功填补这些关键的知识空白。 这里提出的工作的一个主要预期成果是详细的因果关系 将时钟蛋白行为和相互作用与体内时钟表型联系起来的模型。