How bacteria sense and respond to fluid flow

这个项目试图解决生命科学和工程学交叉点上的一个基本问题：细菌如何感知和响应流体流动？水流在自然界中无处不在，比如在河流或动植物循环系统中，在我们的建筑环境中，比如在管道系统中。我们知道液体流动可以显著影响细菌的生活方式，但细菌如何知道他们处于流动的存在中，以及它们如何将这些信息转化为基因表达的变化？这个项目将结合微生物学家(Gitai)和工程师(Stone)的专业知识来回答这个重要的问题。这些研究人员一起证明，一种特定的细菌物种--铜绿假单胞菌--可以积极地感知流动的存在，并建立了系统，以对这些细菌应用特定的流动，并读出细菌对这些流动的反应。目前的研究重点是应用微生物学和工程方法相结合的方法，在分子和生物物理水平上了解这些细菌到底是如何感知和响应周围的流动的。这项研究将建立一个专注于细菌流动传感的新科学领域，称为流变传感，因为Rheo在希腊语中是流动的意思)。这项工作还将推动未来广泛的应用，以了解和操纵细菌在复杂环境中的行为，模拟它们在现实世界中遇到的行为。这项研究的更广泛影响包括研究的内在本质，因为细菌在水环境中的行为对人类活动有一系列影响。其他活动将包括本科生和研究生的培训，以及两名博士后的培训。这个项目将结合微生物学、工程学和物理学的专业知识，以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在很大程度上未被研究的特征。流体流动是细菌环境的普遍特征，包括淡水生态系统、海洋、工业管道和动植物血管或胃肠道系统。Gitai和Stone最近表明，铜绿假单胞菌是一种普遍存在的环境细菌，也可以感染广泛的宿主，它主动感知液体流动，并通过改变基因表达来对流动做出反应。研究人员将这种新的感觉模式称为流变学。此外，他们发现，虽然以前假设流量传感是基于力传感的，但铜绿假单胞菌的流变性传感是不依赖于力的。目前的研究将通过三种平行的方法来确定流变性在铜绿假单胞菌和其他细菌中的作用，这三种方法描述了铜绿假单胞菌流变性的途径，铜绿假单胞菌流变性的生物物理机制，以及铜绿假单胞菌和其他细菌基因组流变性的共性。这个项目将结合生物学和工程学的方法，建立一个新的细菌流动传感领域，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，用于理解对机械提示的力独立反应。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.