PhD project areas for 2007

Molecular, mathematical and synthetic biology of clock gene networks

The biological clock drives 24-hour sleep rhythms in humans, but also controls 5-15% of genes in eukaryotic genomes. This pervasive rhythmicity affects processes ranging from photosynthesis (Dodd et al., Science 2005) and flowering in plants, to solar navigation in birds and butterflies, to cancer risk in mammals. A small network of ~20 genes in the model plant Arabidopsis thaliana generates the rhythms that ultimately control >3000 downstream genes in this species (Edwards et al., Plant Cell 2006). Our group recently used mathematical models of the plant clock to study unexplained data, which we generated using real time reporter gene imaging in intact plants. Simulations using these ODE models predicted the existence and properties of a new clock gene, which we then identified in molecular genetic experiments (Locke et al. Molecular Systems Biology 2005, 2006).

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Project 1 will build upon ongoing experiments, organising diverse data with new controlled vocabularies, extending the models to explain additional results and incorporate further clock components, predicting and then performing the most informative experiments.

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Project 2 will model other plant networks, using new software tools for intuitive and principled model construction. Many important pathways in plants are well-characterised and have proven significance for agriculture, but have never been formally modelled at the molecular level.

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Project 3 will quantify the advantage of correct circadian regulation for plant growth and identify which rhythmic processes are involved, following the earlier demonstration that mis-timing can reduce Arabidopsis growth by 50% (Dodd et al., Science 2005).

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Project 4 will use an artificial biological clock in yeast to create networks where the number of loops is experimentally controlled, allowing us to test theoretical predictions about the advantages of the unexplained complexity in all evolved clock circuits. Enthusiasm for combining experimental and theoretical work will be essential.

To be considered for funding, PhD candidates with EU or UK citizenship should email Prof. Millar (andrew.millar [ at ] ed.ac.uk). You should enclose a CV, names of referees and a 1-2 page statement indicating your interests in systems biology, which of our project(s) most interest you and how you can contribute to our interdisciplinary team. Overseas candidates should contact Prof. Millar only if they have an internationally excellent track record or access to external funding. For further detail on application procedures, please refer to the School's postgraduate pages.

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