Understanding systems-level properties: timely stories from the study of clocks

After several decades dominated by reductionist approaches in biology, researchers are returning to the study of complex biology with a litany of new and old techniques--this paradigm has been termed systems biology. Here we detail how systems biology is being used to uncover complex systems-level properties of the circadian clock. These properties include robustness, periodicity and temperature compensation. We describe how clock researchers are using systems-biology techniques, such as genetic perturbations, kinetic luminescence imaging, synthetic biology and mathematical modelling, to untangle these complex properties in mammals, fungi and bacteria. The strategies developed in the context of circadian clocks may prove useful for tackling similar problems in other systems.