RT Journal Article SR Electronic T1 Data-driven modelling captures dynamics of the circadian clock of Neurospora crassa JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.01.24.477555 DO 10.1101/2022.01.24.477555 A1 Singh, Amit A1 Li, Congxin A1 Diernfellner, Axel C. R. A1 Höfer, Thomas A1 Brunner, Michael YR 2022 UL http://biorxiv.org/content/early/2022/02/19/2022.01.24.477555.abstract AB 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 StatementThe authors have declared no competing interest.