Molecular mechanisms of physical interactions between bacteria and their surroundings

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Project Summary To survive in diverse environments, bacteria must dynamically interact with their physical surroundings to sense and incorporate stimuli into physiological responses. Bacteria often achieve this interplay between extracellular cues and intracellular signaling by using surface-exposed nanomachines that connect the intracellular space to the cell surface. The most broadly distributed surface-exposed nanomachines are appendages called type IV pili (T4P) and evolutionarily related structures that are believed to have diverged from an ancient nanomachine found in the last universal common ancestor. T4P are highly dynamic, employing multiple molecular motors to power cycles of extension and retraction that are essential for many behaviors, making them an ideal system for understanding the dynamic exchange between cells and their physical environments. Despite their broad distribution and importance in many biological processes, little is known about the fundamental biology behind T4P dynamics, regulation, and structure. We will use a combination of genetics, cell biology, biophysics, and biochemical techniques to dissect the fundamental biology of T4P. We will employ multiple model organisms including Caulobacter crescentus, Vibrio cholerae, and Acinetobacter species that all produce T4P for a comparative biology approach across different T4P. Our prior experience and expertise working in these systems will enable us to interrogate how T4P regulatory mechanisms evolve to respond to environmental stimuli and how these regulatory differences influence behavioral outputs. Our five-year goals include understanding the basic mechanisms driving T4P dynamics, how dynamics are regulated, and the consequences of different regulatory mechanisms on bacterial behavior and physiology. This work will address several key questions, including: 1) what are the main factors influencing dynamics? 2) what mechanisms control subcellular localization and patterning? And 3) how do structural subunits of T4P determine their functional and mechanical properties to influence diverse behavioral outputs? This work will provide critical insight into T4P regulation and dynamics that will result in better understanding of the physical interactions between cells and their environments and enable the development of tools to hinder or control T4P function in the broad bacterial behaviors they elicit. The fundamental discoveries made through our study of T4P will also reveal general aspects of biology including insight into the underlying mechanics of molecular motors, the mechanisms controlling intracellular spatial organization, and the relationship between protein structure and function.