Project Reference: TRG27-SLB-JL2

Project title: Single-cell dynamics of the cyanobacterial circadian clock

Project outline

Circadian clocks allow organisms to anticipate daily environmental change. In cyanobacteria, the core 24 hour clock is exceptionally well understood, but in living cells it operates within a wider network of metabolic, stress response and growth pathways that are dynamic and noisy. How the clock coordinates these downstream processes while maintaining reliable behaviour in individual cells remains unclear.

This project will investigate how the circadian clock couples to downstream gene circuits at the single-cell level in Synechococcus. Building on our Green Mother Machine microfluidic platform and recent work showing that the clock can filter environmental fluctuations and modulate pulsatile downstream responses, the student will use long term time-lapse fluorescence imaging to follow clock state, downstream regulators, growth and division in individual cells under precisely controlled environments.

The student will combine dual reporter experiments, quantitative image and time-series analysis, genetic and environmental perturbations, and dynamical and stochastic modelling. They will determine how clock state shapes the timing, amplitude and variability of downstream responses, and when this coupling benefits cellular fitness.

The project sits at the interface of microbiology, microfluidics, single-cell imaging and quantitative biology. It will train the student to move iteratively between experiment and mathematical modelling to uncover general principles by which biological clocks coordinate noisy cellular processes in fluctuating environments.

Principal Supervisor

Professor James Locke

Email address: james.locke@slcu.cam.ac.uk

Department / Partner Institute: Sainsbury Laboratory

Website: https://www.slcu.cam.ac.uk/people/james-locke

BBSRC strategic theme

Understanding the rules of life