Keeping Growing Clocks in Sync

Abstract: The circadian clock, an endogenous near-24 h rhythm that can be entrained to environmental time cues, is a ubiquitous feature of life on Earth. An ancient mechanism for circadian oscillation is found in cyanobacteria, photosynthetic microbes found across the globe. Oscillations are based on cyclic phosphorylation of KaiC molecules, which are coupled together to create coherent bulk oscillations, a phenomenon which can be reconstituted using purified proteins (KaiA, KaiB, KaiC). However, in some cyanobacteria, the growth rate can be as much as 10x the oscillator frequency. In such a situation, the vast majority of protein at the end of a circadian cycle will be new protein that was not present at the beginning of the cycle. We will answer fundamental questions in this system using a combination of theoretical approaches and in vivo and in vitro measurements: How are new KaiC molecules “brought up to speed” without disturbing the frequency? Is this achievable by Kai proteins in isolation or does it require in vivo mechanisms? Is there a fundamental upper limit to the growth rate that is still compatible with oscillation? In addition to studying specific chemical reaction models of the Kai system, we will study the generic effects of growth on coupled oscillator systems by introducing a birth-death process into Kuramoto-like models of coupled phase oscillators to study the transition between phase-locked rhythms and desynchrony.”