Control of cell size and division driven through the circadian clock in cyanobacteria

OpenPlant postdoc Bruno Martins, in Dr James Locke’s lab in the Sainsbury Laboratory, Cambridge, has published and article in PNAS identifying the control that the circadian clock exerts on cell size and division. This could be a first step towards engineering the "rules” of size control in this single-celled organism.


When and at what size to divide are critical decisions, requiring cells to integrate internal and external cues. While it is known that the 24-h circadian clock and the environment modulate division timings across organisms, how these signals combine to set the size at which cells divide is not understood.

Iterating between modeling and experiments, the authors show that, in both constant and light−dark conditions, the cyanobacterial clock produces distinctly sized and timed subpopulations. These arise from continuous coupling of the clock to the cell cycle, which, in light−dark cycles, steers cell divisions away from dawn and dusk. Stochastic modeling allows them to predict how these effects emerge from the complex interactions between the environment, clock, and cell size control.


How cells maintain their size has been extensively studied under constant conditions. In the wild, however, cells rarely experience constant environments. Here, we examine how the 24-h circadian clock and environmental cycles modulate cell size control and division timings in the cyanobacterium Synechococcus elongatus using single-cell time-lapse microscopy. Under constant light, wild-type cells follow an apparent sizer-like principle. Closer inspection reveals that the clock generates two subpopulations, with cells born in the subjective day following different division rules from cells born in subjective night. A stochastic model explains how this behavior emerges from the interaction of cell size control with the clock. We demonstrate that the clock continuously modulates the probability of cell division throughout day and night, rather than solely applying an on−off gate to division, as previously proposed. Iterating between modeling and experiments, we go on to identify an effective coupling of the division rate to time of day through the combined effects of the environment and the clock on cell division. Under naturally graded light−dark cycles, this coupling narrows the time window of cell divisions and shifts divisions away from when light levels are low and cell growth is reduced. Our analysis allows us to disentangle, and predict the effects of, the complex interactions between the environment, clock, and cell size control.

Martins BMC, Tooke AK, Thomas P, Locke JCW. Cell size control driven by the circadian clock and environment in cyanobacteria. PNAS November 27, 2018 115 (48) E11415-E11424; published ahead of print November 8, 2018