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

22 Citations (Scopus)

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

Fingerprint

circadian rhythms
rhythm
Circadian Clocks
Circadian Rhythm
clocks
mice
Clocks
oscillators
Biological Clocks
Physiology
Cell culture
feedback circuits
sleep
Physiological Feedback
insulin
secretions
cycles
physiology
Genes
sustaining

ASJC Scopus subject areas

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

Cite this

D'Alessandro, M., Beesley, S., Kim, J. K., Chen, R., Abich, E., Cheng, W., ... Lee, C. (2015). A tunable artificial circadian clock in clock-defective mice. Nature Communications, 6, [8587]. https://doi.org/10.1038/ncomms9587

A tunable artificial circadian clock in clock-defective mice. / D'Alessandro, Matthew; Beesley, Stephen; Kim, Jae Kyoung; Chen, Rongmin; Abich, Estela; Cheng, Wayne; Yi, Paul; Takahashi, Joseph S.; Lee, Choogon.

In: Nature Communications, Vol. 6, 8587, 30.11.2015.

Research output: Contribution to journalArticle

D'Alessandro, M, Beesley, S, Kim, JK, Chen, R, Abich, E, Cheng, W, Yi, P, Takahashi, JS & Lee, C 2015, 'A tunable artificial circadian clock in clock-defective mice', Nature Communications, vol. 6, 8587. https://doi.org/10.1038/ncomms9587
D'Alessandro M, Beesley S, Kim JK, Chen R, Abich E, Cheng W et al. A tunable artificial circadian clock in clock-defective mice. Nature Communications. 2015 Nov 30;6. 8587. https://doi.org/10.1038/ncomms9587
D'Alessandro, Matthew ; Beesley, Stephen ; Kim, Jae Kyoung ; Chen, Rongmin ; Abich, Estela ; Cheng, Wayne ; Yi, Paul ; Takahashi, Joseph S. ; Lee, Choogon. / A tunable artificial circadian clock in clock-defective mice. In: Nature Communications. 2015 ; Vol. 6.
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