Variation in chemotactic strategies within and across bacterial species

Active Project Grant Awarded Last action

Award ID
R35GM158058
Recipient
Awarding agency
Obligated
$1,171,578

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 30% complete
Place of performance
New Haven, CT 06520, USA

Award details come from USAspending.gov.

Description

Abstract
Bacteria use a conserved signaling pathway to direct their behavior in chemical gradients. This directed motion, called chemotaxis, is essential for clinically relevant phenomena like biofilm formation and host invasion. Extensive work has characterized the dynamics of chemical sensing, adaptation, and behavior in escherichia coli. However, a fully integrated picture of chemotaxis is currently lacking in other bacteria. Given the diversity of sensing and behavioral strategies across bacteria, to fully understand the role of chemotaxis in pathogenicity, IT is essential to characterize the interaction between signal transduction and behavior in other species. In this application, the PI proposes to extend two experimental lines of inquiry first explored in e. Coli, to pathogenic bacteria. One direction of the lab is to use single-cell fluorescence resonance energy transfer to characterize the dynamics of chemotactic signal processing to vibrio cholerae. While e. Coli navigate with 'run- and-tumble' cycles, alternating between straight 'runs', and stationary reorienting 'tumbles', v. Cholerae and other singly-flagellated bacteria navigate with 'run-reverse-flick' cycles, where after a run, cells backtrack along their run trajectory, and then 'flick' at a 90O angle. In a chemical gradient, different swimming behaviors will generate inputs to the chemosensory system with different statistics. Characterizing chemosensory responses in v. Cholerae will reveal how a common signaling architecture can be repurposed to process diverse signals and control diverse chemotaxis strategies. Another direction of the lab is to study the role of cell-to-cell variability in chemotactic behavior and its effect on the collective migration of populations. By consuming environmental attractants, groups of bacteria can establish moving attractant gradients to follow, which results into waves or bands of migrating bacteria that can travel over long distances. For e. Coli, our lab previously demonstrated that during collective migration individual phenotypes spontaneously sort themselves along the traveling gradient according to their chemotactic performance. Importantly, we found that the leader-follower organization that emerges enables traveling populations to, over time, adapt their phenotypic composition to the environments they traverse by culling the weakest phenotypes that end up at the back of the traveling group. Moving forward, we want to understand the dynamics of how new spatial configurations of chemotaxis phenotypes emerge when populations encounter new environments, and the consequences of spatial sorting in migrating populations on pathogenicity. As such, we will examine phenotypic diversity in traveling waves of e. Coli migrating through interfaces between liquid and agar, and of pseudomonas aeruginosa were virulence traits and chemotaxis are often coregulated.

Transactions

Action Obligated Date
Amendment $525,673
Original award $645,905

Quick answers

Who received award R35GM158058?

R35GM158058 was awarded to Yale Univ by National Institute of General Medical Sciences (National Institutes of Health) on May 1, 2025.

How much is award R35GM158058 worth?

$1,171,578 has been obligated on R35GM158058.

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