A tunable artificial circadian clock in clock-defective mice

Matthew D'Alessandro, Stephen Beesley, Jae Kyoung Kim, Rongmin Chen, Estela Abich, Wayne Cheng, Paul Yi, Joseph S. Takahashi, Choogon Lee

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for biological oscillators, but have limited similarity to physiological pathways. Here we report the generation of an artificial, mammalian circadian clock in vivo, capable of generating robust, tunable circadian rhythms. In mice deficient in Per1 and Per2 genes (thus lacking circadian rhythms), we artificially generate PER2 rhythms and restore circadian sleep/wake cycles with an inducible Per2 transgene. Our artificial clock is tunable as the period and phase of the rhythms can be modulated predictably. This feature, and other design principles of our work, might enhance the study and treatment of circadian dysfunction and broader aspects of physiology involving biological oscillators.

Original languageEnglish (US)
Article number8587
JournalNature communications
Volume6
DOIs
StatePublished - Nov 30 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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