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Edinburgh, Scotland, United Kingdom - TAIR

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Unwinding the circadian clock with systems<br />

biology<br />

Systems biology approaches are helping us to understand the complexity of<br />

circadian clock mechanisms, as one of three pilot projects in CSBE. To develop<br />

mathematical models of the clock, we combine timeseries of molecular data and<br />

luciferase reporter imaging, with analysis of clock mutants, and computational<br />

parameter estimation. The models have predicted the properties of unidentified<br />

regulators in the clock and the photoperiod sensor.<br />

Models are now refined by direct comparison to data, and tested for their<br />

robustness to parameter variations. This prioritises our experiments, including<br />

measuring biochemical parameter values (Finkenstadt et al, Bioinformatics 2008;<br />

O’Neill, unpublished).<br />

Mathematical analysis helps us to understand the broad lessons from the<br />

models, and their detailed mechanisms. Single measures of global properties<br />

are useful to compare across species or mutants (flexibility dimension of Rand<br />

et al, Interface 2004, or the functional robustness of Kitano, Mol Syst Biol 2007).<br />

To unpick the biochemistry, we measure how one process, at one time, affects<br />

one specific output. I will illustrate: 1. how the flexibility of timing favours clocks<br />

with multiple feedback loops (Rand et al, J. Theor. Biol. 2006), 2. how complexity<br />

in both the clock and the light input pathways reconfigures the Arabidopsis clock<br />

under different photoperiods (Edwards, Akman and Troein, unpublished), and<br />

how this affects photoperiodism, 3. a new and simpler experimental organism<br />

that facilitates the testing of systems biology models, and that will be broadly<br />

applicable to plant systems biology at the cellular level.<br />

49<br />

L24<br />

Friday 12:00 - 12:30<br />

Systems Biology<br />

Andrew J Millar1<br />

Kieron D Edwards1<br />

Ozgur E Akman1<br />

John O’Neill1<br />

Carl Troein1<br />

Treenut Saithong1<br />

Kevin Stratford2<br />

Bärbel Finkenstadt3<br />

David A Rand3<br />

Francois-Yves Bouget4<br />

1Centre for Systems Biology<br />

at <strong>Edinburgh</strong><br />

University of <strong>Edinburgh</strong><br />

<strong>Edinburgh</strong><br />

EH9 3JR<br />

UK<br />

2<strong>Edinburgh</strong> Parallel<br />

Computing Centre<br />

University of <strong>Edinburgh</strong><br />

<strong>Edinburgh</strong><br />

3Warwick Systems Biology<br />

Centre<br />

University of Warwick<br />

Coventry<br />

CV4 7AL<br />

UK<br />

4CNRS<br />

Banyuls-sur-Mer<br />

France

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