Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Michael Rust, PhD
Associate Professor of Molecular Genetics and Cell Biology and Physics
The University of Chicago

Circadian rhythms are a ubiquitous phenomenon in biology where organisms generate internal, near-24 hour rhythms that anticipate the daily cycling of the environment. Health and fitness defects often occur when this internal rhythm is not synchronized to the external world. To achieve this, circadian clocks are able to maintain a similar oscillator period at different temperatures and growth rates, though the underlying mechanisms are poorly understood. The simplest known circadian clock is found in cyanobacteria where the core ~24 hour oscillator can be reconstituted using purified proteins. I will introduce this system and summarize what is known about the interactions that generate oscillations. I will then argue that the observed behavior of circadian clocks in fluctuating environments can be conceptualized as statements about how phosphorylation trajectories change in this purified system. Using a combination of biochemical measurements and mathematical modeling, I will argue that this system achieves physiological clock behavior through a special architecture where all of the kinetic constants are nearly insensitive to temperature and metabolic changes except for a special control point that allows entrainment while having a minimal effect on timing fates in lung and pancreas cancers.