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.

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Princeton University
United States
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