A systems- and signal-oriented approach to intracellular dynamics.

A mathematical understanding of regulation, and, in particular, the role of feedback, has been central to the advance of the physical sciences and technology. In this article, the framework provided by systems biology is used to argue that the same can be true for molecular biology. In particular, and using basic modular methods of mathematical modelling which are standard in control theory, a set of dynamic models is developed for some illustrative cell signalling processes. These models, supported by recent experimental evidence, are used to argue that a control theoretical approach to the mechanisms of feedback in intracellular signalling is central to furthering our understanding of molecular communication. As a specific example, a MAPK (mitogen-activated protein kinase) signalling pathway is used to show how potential feedback mechanisms in the signalling process can be investigated in a simulated environment. Such 'what if' modelling/simulation studies have been an integral part of physical science research for many years. Using tools of control systems analysis, as embodied in the disciplines of systems biology, similar predictive modelling/simulation studies are now bearing fruit in cell signalling research.