ESR 10: Modelling of collagen receptor clustering and signalling

Host: University of Reading, UK

Supervisory team: Jon Gibbins and Marcus Tindall (University of Reading, UK), Bodo Lange and Christoph Wierling (Alacris Theranostics GmbH, Berlin, Germany), Johan Heemskerk and Marijke Kuijpers, (Maastricht University, Netherlands).

Project locations: University of Reading, UK (Year 1), Alacris Theranostics, Berlin, Germany (Year 2), Maastricht University, Netherlands (Year 3).

Joint PhD Degree: University of Reading and Maastricht University

Project details: In this project mathematical and computational modelling approaches will be used to study the clustering of the platelet collagen receptor.  The goal is to discover new mechanisms and targets for the development of new anti-thrombotic drugs.  Models will be used to understand how clustering occurs, how it is controlled, and the consequences for signal transduction pathways that determine platelet activation.  The goal is to discover new processes, mechanisms or targets for the development of new anti-thrombotic drugs.  Data from multiple sources within the complete programme will be used, making this project a central hub in TAPAS. At the University of Reading, computational and statistical techniques will be used alongside the development of data-driven mathematical models (in the form of ODEs and PDEs) that capture the mechanisms that underlie receptor clustering.  Predictions for new targets to control GPVI clustering will be tested by biological experiments at Maastricht University to validate model predictions. This project will incorporate one year of study at Alacris Theranostics, a leading company in the use of modelling and systems biology platforms to translate the fundamentals of biology into patient benefit.

Relevant references: Dunster, J.L., F.M. Mazet, M.J. Fry, J.M. Gibbins, and M. Tindall. (2015) Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach. PLoS Comp Biol, 11, e1004589.

Mischnik, M., Gambaryan, S., Subramanian, H., Geiger, J., Schütz, C., Timmer, J., and Dandekar, T. (2014) A comparative analysis of the bistability switch for platelet aggregation by logic ODE based dynamical modelling.  Mol Biosyst., 10, 2082-9.

Desirable student skills: Mathematical or computational science, Python programming skills or Matlab experience, basic knowledge of molecular biology.

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