Self versus group-sensing in bacteria

本项目研究群体感应，这是与自然生态系统、农业和医学相关的微生物中广泛存在的细胞间通信过程。群体感应控制微生物的集体行为，如与植物和动物的相互作用、表面生长和抗生素的生产。本文提出的研究将探讨细菌群体中的协调行为如何从单细胞中不同的群体感应机制中产生。这些调查将揭示控制个体之间沟通和合作的一般原则，并将提供在各种生物技术应用中设计或操纵群体感应途径的知识。该项目将在结合生物学和数学方法的跨学科环境中培养多样化的研究生、本科生和高中生。它将进一步为研究生提供科学传播培训和拓展机会，以拓宽他们的技能。群体感应是微生物中普遍存在的一种机制，它通过自我产生的化学信号来协调集体行为。虽然在这一领域取得了重大进展，但我们对群体感应功能的理解仍然存在很大差距。群体感应通常被认为是一种细胞密度依赖/关闭开关，在一个群体中同步基因表达，尽管最近的实验研究表明在细胞尺度上存在很大的反应异质性。该项目将全面表征，在广泛研究的细菌铜绿假单胞菌管理这一群体反应光谱的机制。目的是测试一个区分两种群体感知模式的模型：由细胞外信号反馈介导的群体感知和由细胞内信号反馈介导的自我感知。研究的核心假设是，遗传网络结构和环境因素决定了铜绿假单胞菌的群体感应模式，而群体感应模式反过来又决定了细胞和群体尺度上的反应模式。一系列的实验方法和数学建模将被用来调查这一假设。从这个项目中获得的结果将提供对控制细菌种群决策的原则的系统级理解。它们将在合成生物学的多细胞信号电路的设计、分析和控制中得到应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project investigates quorum sensing, a widespread cell-cell communication process in microbes relevant to natural ecosystems, agriculture, and medicine. Quorum sensing controls collective microbial behaviors such as interactions with plants and animals, growth on surfaces, and production of antibiotics. The studies proposed here will explore how coordinated behaviors in bacterial populations emerge from distinct quorum sensing mechanisms in single cells. These investigations will reveal general principles that govern communication and cooperation between individuals, and will provide the knowledge to engineer or manipulate quorum sensing pathways in a variety of biotechnological applications. The project will train a diverse group of graduate, undergraduate, and high school students in a cross-disciplinary environment that combines biological and mathematical approaches. It will further provide graduate students with science communication training and outreach opportunities to broaden their skill set.Quorum sensing is a ubiquitous mechanism in microbes that coordinates collective behaviors through self-produced chemical signals. Although major advances have been made in this field, there are still large gaps in our understanding of the functional capacity of quorum sensing. Quorum sensing is generally perceived as a cell density-dependent on/off switch that synchronizes gene expression in a population, although recent experimental studies show great response heterogeneity on a cellular scale. This project will holistically characterize the mechanisms that govern this spectrum of quorum responses in the widely studied bacterium Pseudomonas aeruginosa. The objective is to test a model that distinguishes between two quorum-sensing modes: group-sensing mediated by extracellular signal feedback, and self-sensing mediated by intracellular signal feedback. The central hypothesis is that genetic network architecture and environmental factors determine the quorum-sensing mode in P. aeruginosa, which in turn shapes response patterns at cellular and population scales. A range of experimental approaches and mathematical modeling will be employed to investigate this hypothesis. The results attained from this project will provide a systems-level understanding of the principles that govern decision-making in bacterial populations. They will find application in the design, analysis, and control of multicellular signaling circuits in synthetic biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.