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Systems level analysis of platelet signalling


About This PhD Project

Project Description

We are interested in how intracellular signal transduction networks bring about complex biological behaviours in cells. We do this by combining computational biology with wet laboratory experimentation. We are currently using human platelets as our model system to study as they have been widely studied and characterised and are important in both normal haemostasis and in cardiovascular disease. Data about the signalling pathways is mined from the literature to build draft interaction networks. These are then used to build computational models using a range of tools including MatLab, COPASI and VCell. We then use a range of experimental techniques to capture tim- rich data on the evolution of signalling in resting and activated platelets including high-density Western blotting, the use of selective inhibitors, FACS, mass spectrometry, aggregation and secretion assays, and confocal and super resolution microscopy. The output from model simulations are compared with the experimental data to determine their match. Failure to fit leads to the generation of new hypotheses, model refinement and further experimentation to try to understand the complex signalling events and how they lead to both normal platelet signalling and to how this goes wrong in disease state.

References

Regulation of Early Steps of GPVI Signal Transduction by Phosphatases: A Systems Biology Approach. https://www.ncbi.nlm.nih.gov/pubmed/26584182; A high-density immunoblotting methodology for quantification of total protein levels and phosphorylation modifications. https://www.ncbi.nlm.nih.gov/pubmed/26592927

Web link: http://www.reading.ac.uk/biologicalsciences/about/staff/m-j-fry.aspx

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