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

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...

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Autores principales:	Vojtěch Kumpošt, Daniela Vallone, Srinivas Babu Gondi, Nicholas S. Foulkes, Ralf Mikut, Lennart Hilbert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/89479f096ad341f3a593b7195993ccfb
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spelling	oai:doaj.org-article:89479f096ad341f3a593b7195993ccfb2021-12-02T16:08:07ZA stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light10.1038/s41598-021-93913-22045-2322https://doaj.org/article/89479f096ad341f3a593b7195993ccfb2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93913-2https://doaj.org/toc/2045-2322Abstract 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.Vojtěch KumpoštDaniela ValloneSrinivas Babu GondiNicholas S. FoulkesRalf MikutLennart HilbertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vojtěch Kumpošt Daniela Vallone Srinivas Babu Gondi Nicholas S. Foulkes Ralf Mikut Lennart Hilbert A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
description	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.
format	article
author	Vojtěch Kumpošt Daniela Vallone Srinivas Babu Gondi Nicholas S. Foulkes Ralf Mikut Lennart Hilbert
author_facet	Vojtěch Kumpošt Daniela Vallone Srinivas Babu Gondi Nicholas S. Foulkes Ralf Mikut Lennart Hilbert
author_sort	Vojtěch Kumpošt
title	A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
title_short	A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
title_full	A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
title_fullStr	A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
title_full_unstemmed	A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
title_sort	stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/89479f096ad341f3a593b7195993ccfb
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A stochastic oscillator model simulates the entrainment of vertebrate cellular clocks by light

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