Using systematic computational approaches to elucidate the molecular and network dynamics underlying a circadian clock

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Circadian clocks govern the daily rhythms of organisms across the kingdoms of life, and clock defects can impact the health of both individuals and ecosystems. This project uses computational models tied closely to biochemical experiments to better understand how circadian clocks work at the molecular level. Pursuit of this research objective will contribute to interdisciplinary training of graduate and undergraduate students. This, in turn, will enable efforts to expose younger students to STEM topics: continuation of a highly successful program that places high school juniors in laboratories at the University of Chicago for summer research and the update of a course for Illinois public school teachers that presents inexpensive, hands-on ways of engaging their students and helping them understand the physical laws underlying biology.Remarkably, the core circadian clock of cyanobacteria can be reconstituted in a test tube. This permits well-controlled studies that can be used to tease apart complex behaviors and connect clock function with specific molecular events. By leveraging this system and recent advances in computational methods, major outstanding questions about the clock will be addressed: Does the slow switch of a participating protein’s fold set the timing of the clock? How is information communicated between the part of the clock that encodes the time of day and the motor that keeps it advancing steadily forward? How does the clock maintain a near-24-hour period across conditions that can lead to dramatic changes in elementary reaction rates (i.e., what makes the clock so robust)?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.