Quantitative Studies of Bacterial Chemotaxis: Relationship to Cell Growth Optimization and Metabolic Preferences

细菌在自然栖息地是不断变化的环境条件。为了最大限度地提高它们的生长和生存，它们需要优化对这些变化条件的代谢反应。它们的主要行为反应是改变自身的新陈代谢，通过迁徙来改变自己的位置。对他们来说，迁移是最快的反应方式。趋化性，或细胞偏向于有利于其生存的化学梯度方向的运动，是一种在各种运动细菌中普遍存在的现象。在过去的二十年里，对趋化性背后的生化机制的基本科学理解有了极大的提高。然而，趋化性对生物技术重要性应用的影响在很大程度上被忽视了。pi提出了一套结合实验和理论的研究，旨在解决与生物和生物技术应用中微生物种群行为相关的两个主要问题。l。)随着细胞生长条件的变化，对营养引诱剂的趋化反应是如何变化的？这与非混合环境中细胞生长的优化有何关系？2)。什么是细胞对多种可能相互冲突的趋化刺激的净运动反应，这是如何依赖于细胞代谢偏好的？实验工作将包括使用pi自己设计的两种定量分析来测量细菌的运动。理论工作将包括分析实验观察到的趋化反应对种群增长的影响。从这些研究中获得的基本见解可能对许多重要领域产生影响，例如非混合系统中的微生物种群动态，细胞分离，生物传感器和细胞代谢状态监测。pi被认为非常有资格进行拟议的研究，我建议根据该提案提交的调整后的修订预算为该提案提供三年的资金。

Bacteria in natural habitats are continually changing environmental conditions. In order to maximize their growth and survival, they need to optimize the metabolic response to these varying conditions. Their primary behavioral responses are to modify their own metabolism and to change their location by migration. Migration is the quickest mode of response available to them. Chemotaxis, or the biased movement of cells in the direction of a chemical gradient favorable to their survival, is a phenomena found to be ubiquitous among a variety of motile bacteria. Basic scientific understanding of the biochemical mechanisms underlying chemotaxis has increased tremendously over the past two decades. However, the implications of chemotaxis for applications of biotechnological importance have largely been neglected. The PIs propose a set of combined experimental and theoretical studies intended to address two major questions relevant to microbial population behavior in biological and biotechnological applications. l.) How does the chemotactic response to nutrient attractants change as cell growth conditions are varied, and how is this related to optimization of cell growth in a non-mixed environment? 2.) What is the net cell movement response to multiple, perhaps conflicting, chemotactic stimuli, and how does this depend on cell metabolic preferences? The experimental work will include measurements of bacterial motility using two quantitative assays of the PIs' own design. The theoretical work will involve analysis of the effects of the experimentally observed chemotactic responses on population growth. Fundamental insights gained from these investigation may have implications on a number of important areas, such as microbial population dynamics in non-mixed systems, cell separations, biosensor and the monitoring of cell metabolic states. The PIs are considered to be extremely well qualified to carry out the proposed research and I recommend that this proposal be funded for three years in accordance with the adjusted revised budget submitted with this proposal.