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

Kumpošt, Vojtěch 1; Vallone, Daniela 1; Gondi, Srinivas Babu; Foulkes, Nicholas S. 1; Mikut, Ralf 2; Hilbert, Lennart ORCID iD icon 1,3
1 Institut für Technik der Informationsverarbeitung (ITIV), Karlsruher Institut für Technologie (KIT)
2 Karlsruher Institut für Technologie (KIT)
3 Zoologisches Institut (ZOO), Karlsruher Institut für Technologie (KIT)

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.


Verlagsausgabe §
DOI: 10.5445/IR/1000135422
Veröffentlicht am 19.07.2021
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Automation und angewandte Informatik (IAI)
Institut für Biologische und Chemische Systeme (IBCS)
Zoologisches Institut (ZOO)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 12.2021
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000135422
HGF-Programm 47.14.02 (POF IV, LK 01) Information Storage and Processing in the Cell Nucleus
Erschienen in Scientific reports
Verlag Nature Research
Band 11
Heft 1
Seiten Art.-Nr.: 14497
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 14.07.2021
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