Thermally robust chemotaxis and thermotaxis in Escherichia coli

大肠杆菌的耐热趋化性和趋热性

• 批准号: 7523416
• 负责人: NED S WINGREEN
• 金额: $ 45.43万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7523416
• 关键词: Affect; Antibiotics; Bacteria; Cells; Chemicals; Chemotaxis; Collection; Computer Simulation; Coupled; Data; Dependence; Dependency; Depth; Development; Disease; Engineering; Ensure; Environment; Enzymes; Escherichia coli; Experimental Models; Fluorescence Resonance Energy Transfer; Food; Future; Growth; Health; Human; Individual; Life; Maintenance; Measurement; Measures; Modeling; Modification; Molecular; Motion; Motor; Nutrient; Pathway interactions; Property; Proteins; Public Health; Range; Research; Signal Pathway; Signal Transduction; Study models; Swimming; System; Temperature; Variant; base; data acquisition; mutant; novel; pathogen; receptor; research study; response; sensory stimulus; theories

DESCRIPTION (provided by applicant): In the bacterial environment, temperature variation and temperature gradients are as ubiquitous as chemical variation and gradients. For bacteria, locating the optimal combination of temperature and nutrients is crucial for maximizing growth. Indeed, bacteria perform chemotaxis over a large range of temperatures and perform directed motion in temperature gradients, i.e. perform thermotaxis. In Escherichia coli, chemotaxis and thermotaxis both exploit the same well-characterized signaling network. The specific aim of this research is to develop a predictive, quantitative understanding of the thermal properties of this network. Combining experiment with modeling will help answer several fundamental questions: What network features allow robust chemotaxis over a wide range of temperatures? How does the signaling network allow both chemotaxis and thermotaxis? How do multiple sensory stimuli such as attractants/repellants and temperature changes interact? Our preliminary results indicate that the individual steps of the chemotaxis pathway are temperature dependent, but that at the systems level, these dependencies compensate for one another. To quantify these observations, we will obtain temperature-dependent data on the individual steps of the E. coli chemotactic signaling pathway using single-tethered-cell measurements and multi-cell FRET studies. The existing theory for chemotaxis that we have helped develop will guide efficient data acquisition, and the same theory will be used as the basis for modeling. To determine the molecular mechanism(s) underlying E. coli thermotaxis, and to extend a preliminary thermotaxis model we have developed, the thermotactic response of E. coli will be systematically measured via tethered-cell and FRET studies. All experimental studies will exploit our large pre-existing collection of engineered mutant strains of E. coli. Our results are likely to have significance for many cellular signaling networks. Because temperature potentially affects all components of all signaling pathways, our results may reveal universal mechanisms used by cells to ensure faithful signaling over a range of temperatures. Also, since the chemotaxis network of bacteria has been implicated in infectivity, and is widespread and well conserved among bacteria but is not shared by humans, the pathway presents a potential target for the development of future antibiotics. PUBLIC HEALTH RELEVANCE: The aim of this research is to develop a deeper understanding of the network of proteins that allows bacteria to perform chemotaxis and thermotaxis, that is to sense and swim towards food or a preferred temperature, respectively. We propose to develop such an understanding through closely coupled experimental approaches and computational modeling. From a human health perspective, chemotaxis by bacterial pathogens has been implicated in infectivity and maintenance of disease, and thermotaxis may be implicated as well. Since the chemotaxis/thermotaxis network is widespread and well conserved among bacteria, but is not shared by humans, the pathway presents a potential target for the development of future antibiotics. In addition, as all signaling pathways within living cells must function in the context of fluctuating thermal environments, our efforts may reveal universal mechanisms by which cells ensure faithful signaling.

描述(申请人提供)：在细菌环境中，温度变化和温度梯度就像化学变化和梯度一样普遍存在。对于细菌来说，找到最佳的温度和营养组合对于最大限度地生长至关重要。事实上，细菌在很大的温度范围内执行趋化性，并在温度梯度中执行定向运动，即执行热趋化性。在大肠杆菌中，趋化性和趋热性都利用相同的特征良好的信号网络。这项研究的具体目的是对该网络的热性能进行预测性的、定量的了解。将实验与建模相结合将有助于回答几个基本问题：哪些网络特征允许在广泛的温度范围内进行强大的趋化性？信号网络如何同时允许趋化性和趋热性？多种感官刺激如引诱剂/驱避剂和温度变化是如何相互作用的？我们的初步结果表明，趋化途径的各个步骤与温度有关，但在系统水平上，这些依赖关系相互补偿。为了量化这些观察结果，我们将使用单细胞系留测量和多细胞FRET研究，获得关于大肠杆菌趋化信号通路各个步骤的温度依赖数据。我们帮助开发的现有趋化性理论将指导有效的数据获取，同样的理论将被用作建模的基础。为了确定大肠杆菌趋热的分子机制(S)，并扩展我们建立的初步趋热模型，我们将通过系留细胞和FRET研究系统地测量大肠杆菌的趋热反应。所有的实验研究都将利用我们现有的大量工程突变大肠杆菌菌株。我们的结果可能对许多蜂窝信令网络具有重要意义。由于温度可能影响所有信号通路的所有组成部分，我们的结果可能揭示细胞在一定温度范围内确保忠实信号的通用机制。此外，由于细菌的趋化性网络与感染性有关，并且在细菌中广泛存在且保存良好，但人类并不共享，因此该途径为未来抗生素的开发提供了一个潜在的靶点。公共卫生相关性：这项研究的目的是加深对蛋白质网络的理解，该网络允许细菌执行趋化性和趋热性，即分别感觉和游向食物或首选温度。我们建议通过紧密耦合的实验方法和计算模型来发展这种理解。从人类健康的角度来看，细菌病原体的趋化性与疾病的传染性和维持性有关，也可能与热趋性有关。由于趋化/趋热网络在细菌中广泛存在且保守，但在人类中并不共享，该途径为未来抗生素的开发提供了一个潜在的靶点。此外，由于活细胞内的所有信号通路都必须在波动的热环境中发挥作用，我们的努力可能会揭示细胞确保忠实信号的普遍机制。