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Mechanistic mathematical/computational modelling of the PAR polarity network

Institute of Integrative Biology

Dr N Savage , Applications accepted all year round Self-Funded PhD Students Only

About the Project

Cell function is dependent on cell shape. For example, dendritic spine morphology changes from filopodia, which are thought to be searching structures, to mushroom shaped once a potential synaptic connection is found, increasing the postsynaptic surface. Cell function often requires asymmetry, i.e. the demarcation of an anterior and posterior. This demarcation is termed polarity and is defined as localised concentrations of polarity proteins. The molecular mechanisms by which these proteins become polarised is of great interest as the breakdown of polarity establishment is observed in numerous diseases including cancer and Alzheimer’s disease.

In this project the student will generate and analyse mathematical/computational models of the PAR polarity network. The student will first model the simplistic interactions in order to become familiar with modelling techniques. They will then expand the simple model to include more complex published data. This will enable the student to further their modelling skills and become familiar with the biological literature. The student will work in close collaboration with the Rodriguez Lab, who will be performing the experiments within the project. The student will use modelling to help understand biological data, uncover biological mechanism, predict the outcome of experiments and aid experimental design.

Applicants should have a degree in mathematics, physics or computer science. Students with other degrees must have strong evidence of interest and achievement in mathematics and/or computation.

Funding Notes

The project is open to both European/UK and International students. It is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.

Assistance will be given to those who are applying to international funding schemes.

The successful applicant will be expected to provide the funding for tuition fees and living expenses.

A fee bursary may be available for well qualified and motivated applicants.

Details of costs can be found on the University website:
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Rodriguez J, Peglion F, Martin J, Hubatsch L, Reich J, Hirani N, Gascon Gubieda A, Roffey J, Fernandes AR, St Johnston D, Ahringer J, Goehring NW. aPKC cycles between functionally distinct PAR protein assemblies to drive cell polarity. Developmental Cell 2017, 42(4), 400-415.e9.

Inhibitory GEF Phosphorylation Provides Negative Feedback in the Yeast Polarity Circuit (Journal article)
Kuo, C. -C., Savage, N. S., Chen, H., Wu, C. -F., Zyla, T. R., & Lew, D. J. (2014). Inhibitory GEF Phosphorylation Provides Negative Feedback in the Yeast Polarity Circuit. CURRENT BIOLOGY, 24(7), 753-759. doi:10.1016/j.cub.2014.02.024

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