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Systems biology of mammalian circadian clocks.

Systems Biology is a natural extension of molecular biology and can be defined as biology after identification of key gene(s). Systems-biological research is hence seen as a multistage process, beginning with the comprehensive identification and quantitative analysis of individual system components and their networked interactions and leading to the ability to control existing systems toward the desired state and design new ones based on an understanding of structure and underlying dynamical principles. In this chapter, we take mammalian circadian clocks as a model system and describe systems-biological approaches, including the identification of clock-controlled genes, clock-controlled cis elements, and clock transcriptional circuits driven by functional genomics; the parameter change of clock components followed by quantitative measurement; and the dynamic and quantitative perturbation of the clock and its application to one of the fundamental but yet-unsolved questions: singularity behavior of clocks. As perspective for systems-biological investigations, we also introduce the system-level dynamical questions related to the core of clocks, including delay, nonlinearity, temperature-compensation and synchronization of mammalian circadian oscillator(s), and the system-level information problems related to clocks in the environment, including the internal representation of light change through perfect adaptation and internal representation of day length through photoperiodism in mammals.