Dataset Information

Modeling Reveals a Key Mechanism for Light-Dependent Phase Shifts of Neurospora Circadian Rhythms.

ABSTRACT: Light shifts and synchronizes the phase of the circadian clock to daily environments, which is critical for maintaining the daily activities of an organism. It has been proposed that such light-dependent phase shifts are triggered by light-induced upregulation of a negative element of the core circadian clock (i.e., frq, Per1/2) in many organisms, including fungi. However, we find, using systematic mathematical modeling of the Neurospora crassa circadian clock, that the upregulation of the frq gene expression alone is unable to reproduce the observed light-dependent phase responses. Indeed, we find that the depression of the transcriptional activator white-collar-1, previously shown to be promoted by FRQ and VVD, is a key molecular mechanism for accurately simulating light-induced phase response curves for wild-type and mutant strains of Neurospora. Our findings elucidate specific molecular pathways that can be utilized to control phase resetting of circadian rhythms.

SUBMITTER: Bellman J

PROVIDER: S-EPMC6139607 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Modeling Reveals a Key Mechanism for Light-Dependent Phase Shifts of Neurospora Circadian Rhythms.

Bellman Jacob J Kim Jae Kyoung JK Lim Sookkyung S Hong Christian I CI

Biophysical journal 20180804 6

Light shifts and synchronizes the phase of the circadian clock to daily environments, which is critical for maintaining the daily activities of an organism. It has been proposed that such light-dependent phase shifts are triggered by light-induced upregulation of a negative element of the core circadian clock (i.e., frq, Per1/2) in many organisms, including fungi. However, we find, using systematic mathematical modeling of the Neurospora crassa circadian clock, that the upregulation of the frq g ...[more]

PMID: 30139524

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Project description:BACKGROUND:The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized. METHODOLOGY/PRINCIPAL FINDINGS:We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity 'room' light (?90-150 lux) or moderate light supplemented with bright light (?10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17-94%) and after bright light by 52% (range 12-84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. CONCLUSIONS/SIGNIFICANCE:Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.

Dataset Information

Modeling Reveals a Key Mechanism for Light-Dependent Phase Shifts of Neurospora Circadian Rhythms.

Publications

Modeling Reveals a Key Mechanism for Light-Dependent Phase Shifts of Neurospora Circadian Rhythms.

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