ABSTRACT
In this chapter we wish to illustrate the use of an emerging systems biology approach to link molecular mechanisms to complex spatio-temporal dynamics of signal transduction cascades. We review recent work that combines quantitative measurements and computational modelling of signalling pathways to understand their spatiotemporal dynamics. Universal motifs commonly found in cellular signalling networks are protein-modification cycles, which are catalysed by opposing enzymes, such as a kinase and phosphatase. We demonstrate that simple cycles and cascades can generate complex temporal dynamics, including bistability and damped or sustained oscillations. The spatial separation of opposing reactions within protein-modification cycles results in the intracellular gradients of protein activities. These spatial gradients can guide pivotal physiological processes, such as cell motility and mitosis, but also impose a need for facilitated signal propagation, which involves trafficking of endosomes and signalling complexes along microtubules and travelling waves of phosphorylated kinases. Overall, we demonstrate the potential of systems biology to generate new insight and knowledge with quantitative and predictive explanatory power at the system level.
