Investigating the coupling between the circadian clock, metabolism and the environment in cyanobacteria

This project is available through the MIBTP programme on a competition basis. The successful applicant will join the MIBTP cohort and will take part in all of the training offered by the programme. For further details please visit the MIBTP website - https://warwick.ac.uk/fac/cross_fac/mibtp/

The circadian clock is a fundamental piece of the physiology of the cyanobacterium S. elongatus, an important model organism. Most of its genome exhibits circadian rhythms, i.e. regular 24-h oscillations in expression. The clock therefore regulates many other processes inside the cell, including metabolism, photosynthesis or the cell cycle. It anticipates environmental change, but at the same time it is influenced by a variety of signalling cues. Both light-dark and temperature transitions can reset the clock state, but the effect of these signals on clock proteins is relayed through more fundamental quantities, such as redox metabolites and ATP/ADP ratios. These cues can be said to characterise the global energy state of the cell, but on the other hand the clock controls expression of most photosynthetic and metabolic proteins. This dynamic and bi-directional coupling between the circadian clock and metabolism likely holds the key to understanding the evolutionary significance of clocks at the most fundamental level (1, 2).

General aim and methodology:
The aim of this project is to characterise the cross-talk between the circadian clock and metabolism and understand how this cross-talk coordinates cellular growth under different environmental scenarios. Using fluorescent reporters, the joint dynamics of the clock and metabolic enzymes will be measured at single-cell level through time-lapse microscopy (3). Cellular energetics will be monitored through, for example, ATP/ADP ratiometric reporters that the student will implement. These measurements will provide a comprehensive timeline of physiological and gene expression dynamics throughout the 24-h cycle, which will be tested through environmental perturbations. These results will allow us to understand why clocks offer a selective advantage for some organisms, and thus reveal a mechanistic ‘logic’ that can be applied to other systems.

BBSRC Strategic Research Priority: Understanding the rules of life: Microbiology

Techniques undertaken during the project:
• Single-cell time-lapse microscopy
• Computational work including quantitative image analysis, time-series analysis and writing short routines for automated microscopy acquisition
• Microbiology and molecular genetics