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

Lead Research Organisation: University of Reading
Department Name: Mathematics and Statistics


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.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/N504117/1 30/09/2015 29/09/2019
1641920 Studentship BB/N504117/1 30/09/2015 29/09/2019 Daniel Derrick
Description - Furthered the understanding of the way in which a (Shh, Sonic Hedgehog) protein acts in a signalling role. Described and evaluated how it will form "aggregates" (clusters of proteins) which enhance its delivery of signals. The growth of the aggregates is described over time and how size and other clustering properties will impact its travel as it delivers signals.
- Greatly improved the known rates at which events happen when the signalling protein(s) reaches its destination, and a modelled with detail the sequence of events that follows. Significant changes occur as a result of different amounts of signalling protein reaching its destination within a short time. The production of certain proteins, for instance, react to this signal delivery.
- Recently found in research experiments, it is known that unusual levels of cholesterol within cells (both too much and too small) will impact the way Shh signalling protein will influence certain events when delivered. I produce a model of this reaction and show in detail how this is likely to happen, and give a significant insight into which proteins are most impacted, and which are least.
Exploitation Route The outcome of this research is being written into academic papers, which are soon to be delivered to journals. We may publish as many as 4 papers from this work.
The outcomes provide tools and a considerable insight into some very interesting, and in some parts, recent areas of academic research. I fully expect the outcomes of this research to not only interest those looking into the Shh protein, but also developmental biologists, oncologists, mathematical researchers, and various other fields. This is because Shh is a very interesting and popular area, and my research looked directly at very interesting and important aspects of its roles and properties.
Sectors Agriculture

Food and Drink


Pharmaceuticals and Medical Biotechnology