Predictive mathematical modelling of drug impact in complex and dynamic cell populations

This is a three year BBSRC funded project in association with the Departments of Pathology and Medical Biochemistry at the University of Wales College of Medicine. Value to Warwick is £134K.

This project aims to develop integrated mathematical models for pharmacodynamics and pharmacokinetics that demand innovative biotechnological and mathematical solutions. The project addresses single drug responses in heterogeneous and dynamic cell populations. The work has widespread application in predictive biomedicine and in silico drug screening. It will focus on drug targeting and its link with perturbation of the mammalian cell cycle using novel live-cell behaviour and protein tracking methods together with mathematical models. The biotechnology will support the derivation and validation of non-linear models that present significant challenges for structural identifiability.

The biological driver is to gain real insight from the proposed modelling studies of how the dynamic and temporal interactions of a drug with it's molecular target can i) be effected by the delivery of the agent to the target and ii) impact upon cell proliferation and death.

A successful project will allow for the first time exploration and prediction of the effect of manipulating drug target expression through gene therapy and possible routes for cellular evasion of drug action. A further outcome of this project is to be able to predict the effect of response modifiers and to profile the appearance of resistant sub-populations with defined phenotypes. In essence, the strategy is to make the models capable of developing in silico cell response fingerprints for use in drug discovery.