A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light.

Autor: Kumpošt V; Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.; Institute of Biological and Chemical Systems-Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany., Vallone D; Institute of Biological and Chemical Systems-Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany., Gondi SB; Citrus Biotek, Hyderabad, India., Foulkes NS; Institute of Biological and Chemical Systems-Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany. nicholas.foulkes@kit.edu.; Centre for Organismal Studies Heidelberg, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany. nicholas.foulkes@kit.edu., Mikut R; Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany. ralf.mikut@kit.edu., Hilbert L; Institute of Biological and Chemical Systems-Biological Information Processing, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany. lennart.hilbert@kit.edu.; Department of Systems Biology and Bioinformatics, Zoological Institute, Karlsruhe Institute of Technology, Karlsruhe, Germany. lennart.hilbert@kit.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Jul 14; Vol. 11 (1), pp. 14497. Date of Electronic Publication: 2021 Jul 14.
DOI: 10.1038/s41598-021-93913-2
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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