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Data-driven modelling captures dynamics of the circadian clock of Neurospora crassa

Amit Singh, Congxin Li, Axel C. R. Diernfellner, Thomas Höfer, Michael Brunner
doi: https://doi.org/10.1101/2022.01.24.477555
Amit Singh
1Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
3Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093 Zurich, Switzerland
4Tissue and Tumor Microenvironments Group, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
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Congxin Li
2Theoretical Systems Biology (B086) Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany
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Axel C. R. Diernfellner
1Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
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Thomas Höfer
2Theoretical Systems Biology (B086) Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany
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  • For correspondence: michael.brunner@bzh.uni-heidelberg.de t.hoefer@dkfz-heidelberg.de
Michael Brunner
1Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
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  • For correspondence: michael.brunner@bzh.uni-heidelberg.de t.hoefer@dkfz-heidelberg.de
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Abstract

Eukaryotic circadian clocks are based on self-sustaining, cell-autonomous oscillatory feedback loops that can synchronize with the environment via recurrent stimuli (zeitgebers) such as light. The components of biological clocks and their network interactions are becoming increasingly known, calling for a quantitative understanding of their role for clock function. However, the development of data-driven mathematical clock models has remained limited by the lack of sufficiently accurate data. Here we present a comprehensive model of the circadian clock of Neurospora crassa that describe free-running oscillations in constant darkness and entrainment in light-dark cycles. To parameterize the model, we measured high-resolution time courses of luciferase reporters of morning and evening specific clock genes in WT and a mutant strain. Fitting the model to such comprehensive data allowed estimating parameters governing circadian phase, period length and amplitude, and the response of genes to light cues. Our model suggests that functional maturation of the core clock protein Frequency (FRQ) causes a delay in negative feedback that is critical for generating circadian rhythms.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Figure-4B is added in the manuscript.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 19, 2022.
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Data-driven modelling captures dynamics of the circadian clock of Neurospora crassa
Amit Singh, Congxin Li, Axel C. R. Diernfellner, Thomas Höfer, Michael Brunner
bioRxiv 2022.01.24.477555; doi: https://doi.org/10.1101/2022.01.24.477555
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Data-driven modelling captures dynamics of the circadian clock of Neurospora crassa
Amit Singh, Congxin Li, Axel C. R. Diernfellner, Thomas Höfer, Michael Brunner
bioRxiv 2022.01.24.477555; doi: https://doi.org/10.1101/2022.01.24.477555

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