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Dr. Michael Rust CPCB Seminar

When:
November 14, 2014 @ 11:00 am – 12:00 pm
2014-11-14T11:00:00-05:00
2014-11-14T12:00:00-05:00
Where:
6014 BST3

Host: James Faeder

“Input Processing by a Three-Protein Circadian Clock”

The circadian clock from photosynthetic cyanobacteria presents a remarkable opportunity to understand the origin of systems behavior from underlying biochemical reactions. The ability to reconstitute self-organized stable ~24 hour oscillations in protein phosphorylation using the purified KaiABC proteins makes it possible to directly connect experimental measurements with mathematical models. Multisite phosphorylation of the central protein KaiC serves to regulate feedback loops through complex formation with the effector proteins KaiA and KaiB, resulting in stable limit cycle oscillations. In a physiological context, however, the function of this system is not to produce free-running oscillations, but rather to process a stream of information from the external environment to make predictions about future conditions. I will describe our efforts to biochemically reconstitute these input processing mechanisms and to mathematical modeling the observed dynamics. We have found that the Kai proteins are directly sensitive to metabolites, and that the clock is embedded in a metabolic feedback loop which serves to prepare the physiology of the cell for the rhythmic availability of light. We further show that the response of the system to perturbation can be understood as implementing a Bayesian estimator for the most probable time of day. This estimator generically has a discontinuity near mid-day. KaiC appears to implement this discontinuity biochemically using relaxation oscillator-like dynamics with activating and repressive phosphorylation sites that respond on different timescales.

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