Our laboratory is interested in understanding how cells process information and regulate their own behavior, a phenomenon critical to their survival and proliferation. Information processing and cellular-level regulation are rarely achieved by a single factor but instead require the coordinated action of multiple genes and proteins. How are multiple regulatory molecules orchestrated at a systems level? What are the design principles underlying regulatory circuits, and what are the constraints that shape them? How do regulatory systems evolve while continuing to fulfill their critical cellular roles?
To address these questions, our lab studies signal transduction and regulatory pathways in bacteria, focusing on four general areas: (1) We study the regulatory circuits that control cell cycle progression and cellular asymmetry in Caulobacter crescentus. We use genetics, biochemistry, and computational methods along with new fluorescence microscopy and deep-sequencing methods to dissect cell cycle control. (2) We examine the mechanisms through which bacterial cells evolve new signaling pathways. These studies include experimental investigations of protein evolution both in vitro and in vivo, ancestral protein reconstruction, directed evolution studies, and the design of synthetic signaling circuits. We focus in particular on two-component signaling systems. (3) We investigate toxin-antitoxin systems in bacteria, exploring their induction, mechanisms of action, specificity, and evolution. (4) We are probing the origins and consequences of chromosome structure and organization in bacteria, using microscopy, Hi-C, genetics, and computational/evolutionary analyses.
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