An exciting four year interdisciplinary project at the forefront of developing mathematical modelling methodologies for informing toxicology studies in collaboration with industry!
The aim of the project is to provide a tool which can be confidently used in the early stages of projects to aid compound design and selection in respect of pesticide development, but which is considerably less resource intensive and faster to use than traditional ordinary differential equation (ODE) compartmental models which account for pharmacokinetic and pharmacodynamics (PKPD).
Traditionally compartmental pharmacokinetic pharmacodynamic (PKPD) and physiologically based pharmacokinetic (PBPK) models have been used to describe the absorption, distribution, metabolism and excretion of compounds within the body. PKPD models are gross descriptions of individual physiology (e.g. tissue, blood, gut) comprising a small number of compartments. The concentration of the substance in each compartment is typically described mathematically by a system of first order ODEs. PBPK models extend the physiological descriptions of PKPD models to include more organ specific descriptions (e.g. heart, liver).
Commonly such models are informed by the collection of experimental data from experimental or clinical trials. This project will focus on developing a methodology that utilises currently available data coupled with a parameter free approach which reduces the need for data to be available for informing all model parameters. Model simulations using Matlab will be tested against the outcomes of current known cases and examples, whilst utilising a combination of sensitivity analysis and analytical methods to inform model predictions.
This 4 year EPSRC/Syngenta funded studentship is a joint collaborative project between Dr Marcus Tindall as lead supervisor (Mathematical Biology Group, Department of Mathematics, University of Reading), Prof Philip Aston (Department of Mathematics, University of Surrey) and Dr Steven Webb (Product Safety, Syngenta, Jealott’s Hill). The student will primarily be based in the Mathematical Biology Group at Reading, but have the opportunity to undertake training and visits to both Surrey and Syngenta during the studentship.
This cross-disciplinary project will provide training in mathematical and computational modelling at the Universities of Reading and Surrey, generic research skills training (e.g. writing papers and presenting work at international research meetings) and experience in working at the Mathematical Life Science interface with industry. The successful candidate will learn to use Matlab in modelling the respective toxicological systems and develop a graphical user interface (GUI) to the combined qualitative-quantitative methodology developed during the project allowing non-mathematicians to access it.
The student will have the opportunity to participate in the Syngenta yearly Postgraduate Conference, attend relevant workshops on PKPD/PBPK modelling and parameter free methods, present their work at national and international conferences, interact with other industry members working in the pharmaceutical/toxicology sectors and partake in events organised by the UK Quantitative Systems Pharmacology Network (led by Dr Tindall).
In year three of the PhD the successful candidate will undertake a three-month placement with Syngenta. During this time they will work closely with members of the Syngenta Product Safety Research team and wider Crop Protection Research community to gain critical insight into the workings of product safety and agrochemical research and how their research can impact project decision making and company strategy.
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