Ozgur E. Akman, Maria Luisa Guerriero, Laurence Loewe, and Carl Troein
Complementary approaches to understanding the plant circadian clock
Proceedings of From Biology To Concurrency and back 2010 (FBTC'10)
EPTCS 19, 1–19 (2010)
Abstract:
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.