Weak coupling between intracellular feedback loops explains dissociation of clock gene dynamics

Christoph Schmal, Daisuke Ono, Jihwan Myung, J. Patrick Pett, Sato Honma, Ken Ichi Honma, Hanspeter Herzel, Isao T. Tokuda

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this "presumably transient" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.

Original languageEnglish
Article numbere1007330
Pages (from-to)e1007330
JournalPLoS Computational Biology
Issue number9
Publication statusPublished - Sept 12 2019

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modelling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics


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