Round the clock: circadian gene expression, growth and division in cyanobacteria

Circadian clocks generate autonomous daily rhythms of gene expression in anticipation of daily sunlight and temperature cycles in a variety of organisms. The simples and best characterised of all circadian clocks in nature is the cyanobacterial clock, the core of which consists of just 3 proteins – KaiA, KaiB and KaiC – locked in a 24-h phosphorylation-dephosphorylation loop. Substantial progress has been made in understanding how cells generate and sustain this rhythm, but important questions remain: how does the clock maintain resilience in the face of internal and external fluctuations, how is the clock coupled to other cellular processes and what dynamics arise from this coupling? We address these questions using an interdisciplinary approach combining time-lapse microscopy and modelling. In this talk, I will first characterise the clock’s free-running robustness and explore how the clock buffers environmental noise and genetic mutations. Our stochastic model predicts how the clock filters out such noise, including fast light fluctuations, to keep time while remaining responsive to environmental shifts, revealing also that the wild-type operates at a noise optimum. Next, I will focus on how the clock interacts with the other major cellular cycle, the cell division cycle. Our single-cell data shows that the clock couples to the division rate and expression of cell cycle-dependent factors using both frequency modulation and amplitude modulation strategies, with implications for cell growth and cell size control. Our findings illustrate how simple systems can exhibit complex dynamics, advancing our understanding of the interdependency between gene circuits and cellular physiology.