Dynamical biocontrol systems: insights through mechanistic modelling

Abstract

Dynamical biological systems can be modelled mathematically at many levels, from relatively macroscopic, i.e. aggregating many processes or components into subsystem blocks and associated equations characterizing overall behaviour, to microscopic, i.e. focusing on physical mechanisms at the level of individual molecules and associated unit-process equations reflecting such couplings. Here we examine some representative examples within this spectrum of approaches, illustrating the ways in which various investigators handle data-driven modelling problems associated with drug effects–from mostly blood-borne data; switch-like responses in cell signalling subsystems–from molecular biochemistry data; gene network regulation–from pharmacogenomics data; and tumour-suppressor protein regulation mechanisms–also from molecular biochemistry data. Special attention is given to the latter, as modelling of the potential mechanisms involved in this system is an ongoing investigation in our lab. The biosystem model representations described here demonstrate to varying degrees the power of more microscopic methods for discriminating between alternative mechanistic hypotheses of biocontrol system connectivity and dynamics.