TY - JOUR
T1 - A tunable artificial circadian clock in clock-defective mice
AU - D'Alessandro, Matthew
AU - Beesley, Stephen
AU - Kim, Jae Kyoung
AU - Chen, Rongmin
AU - Abich, Estela
AU - Cheng, Wayne
AU - Yi, Paul
AU - Takahashi, Joseph S.
AU - Lee, Choogon
N1 - Funding Information:
We thank Jongkwon Seo for technical assistance. We also thank Dennis Chang for assistance with manuscript preparation, Charles Badland for graphic design of the model in Fig. 7 and Jodi Slade for the thumbnail image and preparation of the main figures. This work was partially supported by NIH grant DK-090730 (C.L.), a bridge grant from the Department of Biomedical Sciences, FSU (C.L.), and NSF grant DMS-0931642 to the Mathematical Biosciences Institute (J.K.K.).
PY - 2015/11/30
Y1 - 2015/11/30
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms9587
DO - 10.1038/ncomms9587
M3 - Article
C2 - 26617050
AN - SCOPUS:84948677429
SN - 2041-1723
VL - 6
JO - Nature communications
JF - Nature communications
M1 - 8587
ER -