Complementary approaches to understanding the plant circadian clock
Electronic Proceedings in Theoretical Computer Science (EPTCS)
Open Publishing Association
Open access. !c Akman, Guerriero, Loewe and Troein. This work is licensed under the Creative Commons Attribution License.
Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock.
The authors thank Gerben van Ooijen for TopCount data and Jane Hillston and Andrew Millar for their helpful comments. The Centre for Systems Biology at Edinburgh is a Centre for Integrative Systems Biology (CISB) funded by BBSRC and EPSRC, ref. BB/D019621/1. CT is supported by The International Human Frontier Science Program Organization.
This is the final version of the article. Available from the Open Publishing Association via the DOI in this record.
Proceedings - Third Workshop 'From Biology To Concurrency and back', Paphos, Cyprus, 27 March 2010
Vol. 19, pp. 1-19