4 Year MRC PhD Programme: Mathematical modelling of tissue growth and patterning in the presomitic mesoderm: a two coupled oscillator approach.

During somitogenesis, a process that is fundamental to the development of the vertebrate body plan, the embryo sequentially forms pairs of somites at periodic intervals in time. Somites are epithelial spheres that later give rise to the ribs and vertebrae of the skeleton, associated skeletal muscle and some dermis. Cells in the presomitic mesoderm, the tissue from which somites form, have a molecular clock that oscillates on a time scale of the order of hours. Oscillations in individual cells are coupled via nearest neighbour signalling, yielding a tissue-scale, multi-cellular oscillator that regulates the timing with which somites form.

Recent data from the Dale lab show that the cell cycle, which oscillates with a period of the order of 10 hours, is coupled to somitogenesis oscillations. Cyclin dependent kinases, which regulate progression through the cell cycle, also regulate Notch signalling, the periodicity of somitogenesis clock oscillations and somite size [1,2]. These observations suggest a mechanism by which the growth of tissue can be communicated to pattern formation.

In another advance we have developed a suite of signal analysis tools that allow analysis of real-time reporters of clock gene expression [2], yielding large datasets describing spatio-temporal oscillations in PSM tissue explants, in which the effect of perturbations to oscillation dynamics can be quantified..

This project will develop mathematical/computational models that explore the coupling between somitogenesis oscillations and cell cycle oscillations in the context of the exciting new experimental results coming from the lab. We will use the models to test hypotheses regarding the biological role of coupling between the cell cycle and the somitogenesis clock. Models will be validated using data from the real-time reporter experiments.

The student will obtain training in stem cell biology, developmental biology, data analysis and mathematical modelling of the somitogenesis oscillator.