Emergent metabolic coordination and cell-to-cell signaling in bacterial biofilms

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PROJECT SUMMARY Understanding communication among bacteria is a fundamental biological problem with critical implications for public health, especially in the context of bacterial communities known as biofilms. While bacteria are single-celled organisms, biofilms can exhibit many multicellular behaviors through emergent coordination and dynamic cell-to-cell signaling. Such collective behaviors unique to biofilms contribute to their ability to tolerate antibiotics and thrive in nearly any environment. While the advent of next-generation sequencing has ushered in a new appreciation for the broad and ubiquitous roles of bacteria in nature, our understanding of their molecular mechanisms of community coordination remains in its infancy. My overarching goal is to understand how coordinated group behaviors arise in bacterial biofilm communities through previously unexplored cell-to-cell signaling mechanisms, and how these emergent behaviors impart functional community-level benefits. Specifically, over the next five years, my group will use multiscale microscopy, high-throughput approaches, and quantitative genetics to decipher how gene regulation, metabolic adaptation, and microenvironmental feedback give rise to emergent coordination and multicellular behaviors in bacterial biofilms. With this MIRA award, my group will explore these questions by focusing on model Bacillus subtilis biofilms, where we recently used a multiscale microfluidic platform to discover that biofilm bacteria can engage in ion channel-mediated electrochemical cell-to-cell signaling. This discovery, along with other unpublished phenomena discovered by my group, make B. subtilis a powerful system for investigating how emergent behaviors arise in bacterial biofilms from single-cell-level properties such as gene regulatory networks and metabolic adaptation. Our data will inform quantitative models of multicellular phenomena, which will give us a system-level understanding of multicellular behaviors in microbes, as well as suggesting new ways to control biofilms.