Many organisms have molecular clocks that synchronize their physiological processes into rhythms that coincide with the solar day, providing enhanced evolutionary fitness by optimizing energy utilization and coordinating timing of integrated biochemical processes.
Disruption of circadian rhythms in mouse models causes adverse effects by influencing the etiology of psychiatric disorders, diabetes, cardiovascular disease, and cancer. By developing a deeper mechanistic understanding of how clocks function at the molecular level, we hope to capitalize on the temporal regulation of physiology to develop new and innovative strategies to treat a broad spectrum of diseases.
We are pursuing high-resolution structures of mammalian clock protein complexes to understand how interactions between these dedicated 'clock proteins' establish 24-hour timing.
Proteins are not static entities––their dynamic behaviors and post-translational modifications play an important role in setting 24-hour timekeeping.
Cyanobacteria have a simple and elegant timekeeping system, built upon three Kai (cycle) proteins. We are interested in leveraging understanding of this protein-based nanomachine to learn more about the basic, biochemical principles of circadian cycling.