Coupling between Circadian Rhythms and Metaboilsm in Cyanobacteria

蓝藻昼夜节律与代谢之间的耦合

• 批准号: 9116893
• 负责人: Michael Rust
• 金额: $ 29.6万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9116893
• 关键词: Address; Animal Model; Architecture; Bacteria; Bacterial Model; Behavior; Behavioral; Beryllium; Biochemical; Biological Clocks; Cell division; Cells; Circadian Rhythms; Clock protein; Coupled; Coupling; Cyanobacterium; Data; Defect; Dissection; Environment; Enzymes; Feedback; Gene Expression; Genetic; Goals; Growth; Health; Health Care Costs; Hour; Human; Impaired health; In Vitro; Jet Lag Syndrome; Lead; Life; Light; Link; Longevity; Measurement; Measures; Metabolic; Metabolic Control; Metabolic Pathway; Metabolism; Microfluidic Microchips; Modeling; Molecular; Mutation; Nucleotides; Organism; Output; Phase; Physiological; Proteins; Reaction; Role; Signal Transduction; Synechococcus; System; Testing; Tube; Work; analog; biochemical model; biochemical tools; circadian pacemaker; design; fitness; fly; in vivo; mathematical model; mutant; predictive modeling; protein-histidine kinase; reconstitution; reproductive; research study; response; shift work; tool

DESCRIPTION (provided by applicant): Circadian rhythms are daily oscillations in behavior with a nearly 24-hour period that are generated by an internal biological clock. Across many organisms, health and fitness are impaired when the circadian clock does not appropriately synchronize with the daily cycles in the external environment. However, the mechanisms underlying these health costs are not clear. We are pursuing the hypothesis that a key function of the circadian clock is to optimize metabolism in anticipation of predicted changes in the environment. We are combining biophysical and biochemical measurements with experimentally-driven mathematically modeling in the bacterial model organism Synechococcus elongatus to study the interlocking relationships between clocks, metabolism, and organismal fitness. In this organism, the relationship between the clock and metabolism is very direct, and the core circadian oscillator can be reconstituted in a test tube using purified protein, making this an exceptionally power system to study this hypothesis. In Aim 1, we will determine the molecular mechanisms that maintain robust rhythms in the presence of metabolic signals in vitro using purified proteins. In Aim 2, we will determine the metabolic effects of clock mutants in vivo and their role in a metabolic feedback loop coupling clock output to input. In Aim 3, we will determine the impact of misalignment between the clock and metabolism on the reproductive rate and capacity of single cells in order to link these findings to organismal fitness.

描述（由申请人提供）：昼夜节律是由内部生物钟产生的近 24 小时周期的每日行为波动。在许多生物体中，当生物钟与外部环境中的日常周期不适当同步时，健康和健身就会受到损害。 然而，这些健康成本背后的机制尚不清楚。我们正在追求这样的假设：生物钟的一个关键功能是根据环境的预测变化来优化新陈代谢。我们将细菌模型生物细长聚球藻中的生物物理和生化测量与实验驱动的数学建模相结合，以研究生物钟、新陈代谢和生物体适应性之间的连锁关系。在这种生物体中，时钟和新陈代谢之间的关系非常直接，并且可以使用纯化的蛋白质在试管中重建核心昼夜节律振荡器，这使其成为研究这一假设的异常强大的系统。在目标 1 中，我们将使用纯化的蛋白质确定在体外存在代谢信号的情况下维持稳健节律的分子机制。在目标 2 中，我们将确定时钟突变体在体内的代谢效应 以及它们在将时钟输出耦合到输入的代谢反馈环路中的作用。在目标 3 中，我们将确定生物钟和新陈代谢之间的失调对单细胞的繁殖率和能力的影响，以便将这些发现与有机体健康联系起来。