Noise, memory, and adaptation in the flagellum system in E.coli.

大肠杆菌鞭毛系统的噪音、记忆和适应。

• 批准号: 10004140
• 负责人: Philippe Cluzel
• 金额: $ 32.12万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004140
• 关键词: Affect; Automobile Driving; Bacteria; Biological Assay; Biological Models; Biology; Catheters; Cells; Data; Environment; Escherichia coli; Exhibits; Filament; Fluorescence Microscopy; Generations; Genes; Goals; Growth; Health Hazards; Individual; Knowledge; Masks; Medical; Medical Device; Memory; Microbial Biofilms; Microfluidics; Monitor; Noise; Nutrient; Organelles; Physiologic pulse; Population Study; Production; Proteins; Regulator Genes; Resolution; Sigma Factor; System; Techniques; Text; Time; cell growth; cell type; cost; design; fitness; response

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. The long-term goal of this project is to identify and predict the activity of gene regulatory networks (GRN) of highly expressed genes when bacteria need to grow in nutrient-limited environments. To quantitively tackle this problem, we will use as a model system the flagellum GRN in E. coli. While a lot is known about the flagellum GRN, most of our information comes from population studies that mask the regulatory dynamics taking place within uncoordinated single cells. Consequently, this project will make use of well-known fluorescence microscopy techniques and more recent advances in microfluidics to monitor at high-resolution growth and the activity of the flagellum GRN in single cells under different environmental conditions. We have organized this proposal around one of the most intriguing aspect of our preliminary data that demonstrates that the flagellum GRN exhibits pulsating dynamics. We found that the expression of flagellar genes in wild-type cells is either ‘off’ over several generations or is ‘on’ for a much shorter period of time. We propose to determine the growth cost of single pulses in individual cells. This aim will help us to identify how modulating the dynamics of the flagellum GRN activity can be a strategy to optimize both cellular growth and the synthesis of large organelles under nutrient limited conditions. At the completion of this proposal our current knowledge on the flagellum synthesis under nutrient limited conditions will be significantly advanced and we hope that some of the newly identified principles could be used in quantitative biology to optimize the designs of synthetic circuits in fluctuating nutrient-poor environments.

在此处输入文本，该文本是您的应用程序的新摘要信息。此部分的文本长度不得超过 30 行。 该项目的长期目标是当细菌需要在营养有限的环境中生长时，识别和预测高表达基因的基因调控网络（GRN）的活动。为了定量解决这个问题，我们将使用大肠杆菌中的鞭毛 GRN 作为模型系统。 虽然人们对鞭毛 GRN 了解很多，但我们的大部分信息都来自群体研究，这些研究掩盖了不协调的单细胞内发生的调控动态。因此，该项目将利用众所周知的荧光显微镜技术和微流体学的最新进展来监测不同环境条件下单细胞鞭毛 GRN 的高分辨率生长和活性。我们围绕初步数据中最有趣的方面之一组织了这项提案，该方面表明鞭毛 GRN 表现出脉动动力学。我们发现，野生型细胞中鞭毛基因的表达要么在几代内“关闭”，要么在更短的时间内“开启”。我们建议确定单个细胞中单个脉冲的生长成本。这一目标将帮助我们确定如何调节鞭毛 GRN 活性的动态成为在营养有限的条件下优化细胞生长和大型细胞器合成的策略。 该提案完成后，我们目前对营养有限条件下鞭毛合成的了解将得到显着提高，我们希望一些新确定的原理可以用于定量生物学，以优化波动营养贫乏环境中合成回路的设计。