title: Systems Biology-Derived Discoveries of Intrinsic Clocks.
abstract: A systems approach to studying biology uses a variety of mathematical, computational, and engineering tools to holistically understand and model properties of cells, tissues, and organisms. Building from early biochemical, genetic, and physiological studies, systems biology became established through the development of genome-wide methods, high-throughput procedures, modern computational processing power, and bioinformatics. Here, we highlight a variety of systems approaches to the study of biological rhythms that occur with a 24-h period-circadian rhythms. We review how systems methods have helped to elucidate complex behaviors of the circadian clock including temperature compensation, rhythmicity, and robustness. Finally, we explain the contribution of systems biology to the transcription-translation feedback loop and posttranslational oscillator models of circadian rhythms and describe new technologies and "-omics" approaches to understand circadian timekeeping and neurophysiology.
authors.affiliation: Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center , Suita, Osaka , Japan.
authors.forename: Arthur
authors.initials: A
authors.lastname: Millius
authors.affiliation: Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center, Suita, Osaka, Japan; Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroki R
authors.initials: HR
authors.lastname: Ueda
keywords: RNA sequencing; circadian rhythm; models; neurophysiology; ribosome profiling; systems biology; theory