How bacteria sense and respond to fluid flow

该项目旨在解决生命科学与工程交叉的一个基本问题：细菌如何感知和响应流体流动？在自然界中，如河流或动植物循环系统中，以及在我们的建筑环境中，如管道中，流动无处不在。我们知道液体流动可以显著影响细菌的生活方式，但细菌是如何知道它们在流体中存在的？它们是如何将这些信息转化为基因表达的变化的？这个项目将通过结合微生物学家（Gitai）和工程师（Stone）的专业知识来回答这个重要的问题。这些研究人员共同表明，一种特殊的细菌，铜绿假单胞菌，可以积极地感知水流的存在，并建立了系统，既可以将特定的水流应用于这些细菌，又可以读取细菌对这些水流的反应。目前的研究重点是应用微生物学和工程方法的结合来了解，在分子和生物物理水平上，这些细菌究竟是如何感知和响应周围的流动的。这项研究将建立一个新的科学领域，专注于细菌流量传感称为流变传感，因为rheo是希腊语的流动)。这项工作还将推动广泛的未来应用，以理解和操纵细菌在复杂环境中的行为，模仿它们在现实世界中遇到的行为。研究的广泛影响包括研究的内在性质，因为水生环境中细菌的行为对人类活动有许多影响。额外的活动将包括培养本科生和研究生，以及两名博士后。将开展针对K12学生和普通民众的各种外展活动。该项目将结合微生物学、工程学和物理学的专业知识来了解细菌如何感知和响应流体流动，这是细菌环境的一个重要但尚未充分研究的特征。流体流动是细菌环境的普遍特征，包括淡水生态系统、海洋、工业管道、动植物血管系统或胃肠道系统。Gitai和Stone最近的研究表明，铜绿假单胞菌（Pseudomonas aeruginosa）是一种普遍存在的环境细菌，也可以感染多种宿主，它能主动感知流体流动，并通过改变基因表达对流体流动做出反应。研究人员将这种新的感觉方式称为流变感应。此外，他们还发现，虽然以前认为流量传感是基于力传感的，但铜绿假单胞菌的流变传感是与力无关的。目前的研究将通过三个平行的方法来确定流变感应在铜绿假单胞菌和其他细菌中是如何工作的，这三个平行的方法描述了铜绿假单胞菌流变感应的途径，铜绿假单胞菌流变感应的生物物理机制，以及铜绿假单胞菌和其他细菌基因组中流变感应的普遍性。该项目将整合生物和工程方法，建立一个新的细菌流量传感领域，这将对理解细菌生理学和生态学产生重大影响，并建立一个新的系统来理解对机械线索的力无关反应。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 seeks to address a fundamental problem at the intersection of life science and engineering: how do bacteria sense and respond to fluid flow? Flows are everywhere in both nature, as in rivers or plant and animal circulatory systems, and in our built environments, as in plumbing. We know that fluid flows can significantly affect bacterial lifestyles, but how do bacteria know that they are in the presence of flow and how do they transduce that information into changes in gene expression? This project will answer this important question by combining the expertise of a microbiologist (Gitai) and an engineer (Stone). Together these investigators have shown that a specific bacterial species, Pseudomonas aeruginosa, can actively sense the presence of flow and have built systems to both apply specific flows to these bacteria and to read out how bacteria respond to these flows. The current research is focused on applying a combination of microbiology and engineering approaches to understand, at the molecular and biophysical levels, how exactly these bacteria sense and respond to the flow around them. This research will establish a new area of science focused on bacterial flow-sensing termed rheosensing, as rheo is Greek for flow). This work will also advance a wide range of future applications for understanding and manipulating bacterial behaviors in complex environments that mimic those that they encounter in the real world. The Broader Impact of the research include the intrinsic nature of the research, as the behavior of bacteria in aquatic environments have a host of implications to human activities. Additional activities will involve the training of undergraduate and graduate students, along with two post-docs. Various outreach programs targeting K12 students and the general public will be carried out.This project centers on combining expertise in microbiology, engineering, and physics to understand how bacteria sense and respond to fluid flow, which is an important yet largely understudied feature of bacterial environments. Fluid flow is a ubiquitous feature of bacterial environments, including freshwater ecosystems, oceans, industrial plumbing, and plant and animal vasculature or gastrointestinal systems. Gitai and Stone have recently shown that Pseudomonas aeruginosa, a ubiquitous environmental bacterium that can also infect a wide range of hosts, actively senses fluid flow and responds to flow by altering gene expression. The investigators termed this new sensory modality rheosensing. Furthermore, they found that whereas flow sensing was previously assumed to be based on force-sensing, P. aeruginosa rheosensing is force-independent. The current research will determine how rheosensing works in P. aeruginosa and in other bacteria through three parallel approaches that characterize the pathway responsible for P. aeruginosa rheosensing, the biophysical mechanism of P. aeruginosa rheosensing, and the generality of rheosensing across the genomes of P. aeruginosa and other bacteria. Together this project will integrate biological and engineering approaches to establish a new field of bacterial flow-sensing that will have significant impacts on both understanding bacterial physiology and ecology, and establish a new system for understanding force-independent responses to mechanical cues.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.