Theory of Living Matter Group

We are studying the mechanistic basis of epigenetic regulation in the Polycomb system, a vital epigenetic silencing pathway that is widely conserved from flies to plants to humans. We use the process of vernalization in plants in our experiments, which involves memory of winter cold to permit flowering only when winter has passed via quantitative epigenetic silencing of the floral repressor FLC. Utilising this system has numerous advantages, including slow dynamics and the ability to read out mitotic heritability of expression states through clonal cell files in the roots. Using mathematical modelling and experiments (including ChIP and fluorescent reporter imaging), we have shown that FLC cold-induced silencing is essentially an all-or-nothing (bistable) digital process. The quantitative nature of vernalization is generated by digital chromatin-mediated FLC silencing in a subpopulation of cells whose number increases with the duration of cold. We have further shown that Polycomb-based epigenetic memory is indeed stored locally in the chromatin (in cis) via a dual fluorescent labelling approach. I will also discuss how further predictions from the modelling, including opposing chromatin modification states and physical coupling of activators and de-repressors, have been verified. Finally, I will discuss how such digital control can be integrated with more conventional analogue transcriptional regulation to generate chromatin states that are either instructive or responsive depending on the strength of the analogue regulation.

The circadian clock orchestrates gene regulation across the day/night cycle in a wide range of organisms, from cyanobacteria to mammals. The core mechanism of the clock has been worked out, with one or more feedback loops generating the 24 h oscillation in gene expression. However, the clock can drive and receive input from diverse cellular processes, including the cell cycle, stress response, and metabolism. How does the clock integrate signals from these diverse inputs to produce a robust output? How is clock information coordinated between cells? To address these questions we are using the common tools of mathematical modelling, synthetic biology, and single cell time-lapse microscopy on two model organisms, the cyanobacterium Synechococcus elongatus, and the model plant Arabidopsis. I will present our work examining how and why clocks are coupled, both between cells and to other gene networks.