Coupling between Circadian Rhythms and Metaboilsm in Cyanobacteria

蓝藻昼夜节律与代谢之间的耦合

基本信息

批准号：
8560513
负责人：
Michael Rust
金额：
$ 29.36万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
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/8560513
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 Plastics Proteins Reaction Role Signal Transduction Synechococcus System Testing Tube Work analog biochemical model circadian pacemaker design fitness fly in vivo mathematical model mutant predictive modeling protein-histidine kinase public health relevance reconstitution reproductive research study response shift work tool

项目摘要

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）：昼夜节律是行为的每日振荡，其内部生物钟产生了近24小时。在许多生物体中，当昼夜节律时钟与外部环境中的每日周期没有适当同步时，健康和健身会受到损害。但是，这些健康成本的基础机制尚不清楚。我们追求的假设是，昼夜节律的关键功能是在预测环境变化的情况下优化新陈代谢。我们正在将生物物理和生化测量与实验驱动的细菌模型生物体中的数学建模相结合，以研究时钟，代谢和生物体适应性之间的互锁关系。在这种生物体中，时钟和代谢之间的关系非常直接，可以使用纯化的蛋白质将核心昼夜节律振荡器重构在试管中，这使得这是研究该假设的异常动力系统。在AIM 1中，我们将确定使用纯化蛋白质在代谢信号的情况下保持稳健节奏的分子机制。在AIM 2中，我们将确定体内时钟突变体的代谢作用它们在代谢反馈回路耦合时钟输出与输入中的作用。在AIM 3中，我们将确定时钟和代谢之间的未对准对单个细胞的生殖速率和能力的影响，以将这些发现与有机体适应性联系起来。