CSBE Circadian Rhythms

Professor Andrew Millar, Chair of Systems Biology in the School of Biological Sciences and Director of the Centre for Systems Biology at Edinburgh, combines molecular, physiological, and mathematical approaches in his research on the circadian clock in Arabidopsis thaliana.

The circadian clock lends itself ideally to systems-level research, and is becoming a paradigm for systems biology. The 24h rhythms in model vertebrate, invertebrate, fungal and plant species emerge from the interactions of a tractable number (10-20) of clock genes and proteins. These form a network of interlocking, positive- and negative-feedback loops. Light- and temperature-signalling pathways also regulate some clock genes or proteins, on a timescale of minutes, in order to synchronise the molecular rhythms with the external, day/night cycle. The interaction of environmental and endogenous rhythms, fast and slow timescales creates complex dynamics.

Professor Andrew Millar’s group was the first to model the plant clock mechanism based on data from reporter genes, microarrays, RNA and protein expression profiles, from multiply-mutant plants and environmental perturbations. This analysis invalidated a single-loop network proposed earlier, led to the prediction of hypothetical components in a multi-loop structure, and allowed us to identify one of the new components in experiments. CSBE is refining these mechanistic models using a range of dynamic perturbations and direct measurements of kinetic parameters.

Comparative analysis of clock models from several species suggests the principles that underlie their shared properties, for example giving multiple-loop clock circuits an evolutionary advantage. The circadian system has major effects on the whole organism, because it drives the rhythmic expression of over 10% of all genes in most eukaryotes, thereby controlling pervasive rhythms in metabolism, physiology and behaviour. Correct circadian timing substantially increases plant growth rates, with potential applications in crop improvement, and can affect human health by increasing the effectiveness of cancer chemotherapy, or contributing to relieve jet lag, for example.

CSBE Circadian Rhythms