Uncovering mechanisms of temperature compensation through generation and analysis of an ensemble of models consistent with experimental data

Faculty Mentor: Michael Rust (University of Chicago)

Circadian clocks maintain stable 24-hour rhythms despite temperature fluctuations, yet they must also remain sensitive enough to be synchronized by external environmental cues—a biological paradox that remains poorly understood. This project investigates the molecular mechanisms of this temperature compensation using the cyanobacterial circadian clock, a system that can be precisely reconstituted and studied in a test tube. By developing an advanced computational framework that uses constrained Langevin dynamics to efficiently fit complex models to experimental data, the researchers aim to quantify how specific temperature-sensitive protein interactions counteract one another. Ultimately, this work seeks to provide a definitive dynamical systems description of how biological clocks achieve reliable timekeeping across varying environmental conditions.