Locke, James C. W. (2006) A systems biology approach to the Arabidopsis circadian clock. PhD thesis, University of Warwick.

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Abstract

Circadian clocks involve feedback loops that generate rhythmic expression of key
genes. Molecular genetic studies in the higher plant Arabidopsis theliene have revealed
a complex clock network. We begin by modelling the first part of the Arabidopsis clock
network to be identified, a transcriptional feedback loop comprising TIMING OF CAB
EXPRESSION 1 (TOCl), LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN
CLOCK ASSOCIATED 1 (CCA1). As for many biological systems, there are no experimental
values for the parameters in our model, and the data available for parameter
fitting is noisy and varied. To tackle this we construct a cost function, which quantifies
the agreement between our model and various key experimental features. We then
undertake a global search of parameter space, to test whether the proposed circuit can
fit the experimental data. Our optimized solution for the Arabidopsis clock model is
unable to account for significant experimental data. Thanks to our search of parameter
space, we are able to interpret this as a failure of the network architecture.
We develop an extended clock model that is based upon a wider range of data
and accurately predicts additional experimental results. The model comprises two interlocking
feedback loops comparable to those identified experimentally in other circadian
systems. We propose that each loop receives input signals from light, and that each
loop includes a hypothetical component that had not been explicitly identified. Analysis
of the model predicts the properties of these components, including an acute light
induction at dawn that is rapidly repressed by LHY and CCAL We find this unexpected
regulation in RNA levels of the evening-expressed gene GIGANTEA (GI), supporting our
proposed network and making GI a strong candidate for this component.
We go on to develop reduced models of the Arabidopsis clock to aid conceptual
understanding, and add a further proposed feedback loop to develop a 3-loop model of
the circadian clock. This 3-loop model is able to reproduce further key experimental
data.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QK Botany Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Circadian rhythms -- Mathematical models, Systems biology, Arabidopsis thaliana, Molecular genetics
Official Date:	March 2006
Institution:	University of Warwick
Theses Department:	Department of Physics
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Turner, Matthew S.; Milllar, A. J. (Andrew J.)
Extent:	xiii, 139 leaves
Language:	eng

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