Analysis of a combined cholesterol and sonic hedgehog signalling pathway using mathematical modelling

In recent years the Mathematical Biology Group at the University of Reading, in collaboration with colleagues at Syngenta has been developing mathematical models of the mevalonate pathway - a key regulatory pathway in cholesterol biosynthesis. Cholesterol biosynthesis is vital for cell membrane integrity and overall well-being of the host and is universal across plant and animal cell systems. CYP51 is a key component of the pathway and its inhibition is thought to have adverse effects on it. In recent work the groups at Reading and Syngenta have demonstrated, using mathematical modelling, the robustness of the signalling cascade to variation in cholesterol and CYP51 inhibition.

This project will extend this work to consider what affects CYP51 has on cell development. This will involve integration of the sonic hedgehog pathway, a key pathway responsible for cell development, and the cross-talk between it and the mevalonate pathway. Our current nonlinear ordinary differential equation will be extended with a similar model of the hedgehog pathway. It will be parameterised using data from the literature and solved numerically using available numerical solvers (e.g. Matlab). Model analysis will include the use of model reduction, asymptotic perturbation and dynamical systems techniques.