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Low-dimensional Dynamics of Two Coupled Biological Oscillators
Colas Droin1, Eric R Paquet1, Felix Naef1
1Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne CH-1015, Switzerland.
Nature Physics
|June 13, 2020
Summary
The circadian clock and cell cycle synchronize via a novel stochastic model. This interaction explains conserved phase-locked states across species and links cellular proliferation to tissue-level circadian rhythms.
Area of Science:
- Cellular Biology
- Systems Biology
- Biophysics
Background:
- The circadian clock and cell cycle are fundamental cellular oscillators.
- These processes are known to interact and synchronize within cells.
- Understanding this coupling is crucial for deciphering cellular dynamics and physiological rhythms.
Purpose of the Study:
- To develop a method for modeling the coupled circadian clock and cell cycle system.
- To infer the non-linear dynamics and coupling strength from single-cell data.
- To investigate the properties and physiological relevance of the synchronized states.
Main Methods:
- Development of a low-dimensional stochastic model.
- Inference of model parameters from time-lapse fluorescence microscopy of mouse and human cells.
- Experimental validation of predicted phase-shifts in the 1:1 phase-locked state.
Main Results:
- Identified multiple phase-locked states between the circadian clock and cell cycle.
- Demonstrated robustness of these states against molecular noise.
- Validated predicted phase-shifts experimentally and showed temperature independence.
- Confirmed evolutionary conservation of these states from mouse to human.
- Linked coupled dynamics to observed circadian phase shifts in tissues with varying proliferation rates.
Conclusions:
- A novel stochastic model effectively captures the coupled dynamics of the circadian clock and cell cycle.
- Phase-locked states are a conserved and robust feature of this coupled system.
- The interplay between these oscillators has implications for tissue physiology and circadian rhythm regulation.
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