PUBLICATION
A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
- Authors
- Kumpošt, V., Vallone, D., Gondi, S.B., Foulkes, N.S., Mikut, R., Hilbert, L.
- ID
- ZDB-PUB-210716-3
- Date
- 2021
- Source
- Scientific Reports 11: 14497 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Butadienes/pharmacology
- Cells, Cultured
- Circadian Rhythm/drug effects
- Circadian Rhythm/physiology*
- Colforsin/pharmacology
- Cyclic CMP/analogs & derivatives
- Cyclic CMP/pharmacology
- Luminescent Measurements
- MAP Kinase Signaling System/drug effects
- MAP Kinase Signaling System/physiology
- Models, Biological*
- Nitriles/pharmacology
- Reproducibility of Results
- Single-Cell Analysis
- Stochastic Processes
- Zebrafish*/genetics
- PubMed
- 34262086 Full text @ Sci. Rep.
Citation
Kumpošt, V., Vallone, D., Gondi, S.B., Foulkes, N.S., Mikut, R., Hilbert, L. (2021) A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light. Scientific Reports. 11:14497.
Abstract
The circadian clock is a cellular mechanism that synchronizes various biological processes with respect to the time of the day. While much progress has been made characterizing the molecular mechanisms underlying this clock, it is less clear how external light cues influence the dynamics of the core clock mechanism and thereby entrain it with the light-dark cycle. Zebrafish-derived cell cultures possess clocks that are directly light-entrainable, thus providing an attractive laboratory model for circadian entrainment. Here, we have developed a stochastic oscillator model of the zebrafish circadian clock, which accounts for the core clock negative feedback loop, light input, and the proliferation of single-cell oscillator noise into population-level luminescence recordings. The model accurately predicts the entrainment dynamics observed in bioluminescent clock reporter assays upon exposure to a wide range of lighting conditions. Furthermore, we have applied the model to obtain refitted parameter sets for cell cultures exposed to a variety of pharmacological treatments and predict changes in single-cell oscillator parameters. Our work paves the way for model-based, large-scale screens for genetic or pharmacologically-induced modifications to the entrainment of circadian clock function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping