bims-ciryme 2025-04-20 papers

EMBO J. 2025 Apr 17.

Quantitative measures of clock protein dynamics in the mouse suprachiasmatic nucleus extends the circadian time-keeping model.

Nicola J Smyllie, Alex A Koch, Antony D Adamson, Andrew P Patton, Adam Johnson, James S Bagnall, Olivia Johnson, Qing-Jun Meng, Andrew S I Loudon, Michael H Hastings.

The suprachiasmatic nucleus (SCN) synchronises circadian rhythmicity (~24 h) across the body. The SCN cell-autonomous clock is modelled qualitatively as a transcriptional-translational feedback loop (TTFL), with heteromeric complexes of transcriptional activator and repressor proteins driving cyclical gene expression. How these proteins really behave within the SCN, individually and in relation to each other, is poorly understood. Imaging SCN slices from a novel array of knock-in reporter mice, we quantify the dynamic behaviours of combined repressors PERIOD2 (PER2) and CRYPTOCHROME1 (CRY1), and activator BMAL1. We reveal a spectrum of protein-specific intracellular and spatiotemporal behaviours that run counter to the qualitative TTFL model. We also show that PER and CRY1 exert independent actions on TTFL oscillations, and that their individual stabilities play a critical role in SCN circadian dynamics. These results reveal a rich and unanticipated complexity in the dynamic behaviours and functions of endogenous circadian proteins, prompting re-appraisal of current transcriptional-translational feedback loop models of the suprachiasmatic nucleus.

Keywords: CRY1; E-box; PER2; Suprachiasmatic Nucleus; TTFL

DOI: https://doi.org/10.1038/s44318-025-00426-z

Nat Commun. 2025 Apr 15. 16(1): 3566

Environmental and molecular noise buffering by the cyanobacterial clock in individual cells.

Aleksandra Eremina, Christian Schwall, Teresa Saez, Lennart Witting, Dietrich Kohlheyer, Bruno M C Martins, Philipp Thomas, James C W Locke.

Circadian clocks enable organisms to anticipate daily cycles, while being robust to molecular and environmental noise. Here, we show how the clock of the cyanobacterium Synechococcus elongatus PCC 7942 buffers genetic and environmental perturbations through its core KaiABC phosphorylation loop. We first characterise single-cell clock dynamics in clock mutants using a microfluidics device that allows precise control of the microenvironment. We find that known clock regulators are dispensable for clock robustness, whilst perturbations of the core clock reveal that the wild type operates at a noise optimum that we can reproduce in a stochastic model of just the core phosphorylation loop. We then examine how the clock responds to noisy environments, including natural light conditions. The model accurately predicts how the clock filters out environmental noise, including fast light fluctuations, to keep time while remaining responsive to environmental shifts. Our findings illustrate how a simple clock network can exhibit complex noise filtering properties, advancing our understanding of how biological circuits can perform accurately in natural environments.

DOI: https://doi.org/10.1038/s41467-025-58169-8

NPJ Metab Health Dis. 2025 ;3(1): 15

Potential bidirectional communication between the liver and the central circadian clock in MASLD.

Frédéric Gachon, Elisabetta Bugianesi, Gabriele Castelnuovo, Henrik Oster, Julie S Pendergast, Sara Montagnese.

Most aspects of physiology and behaviour fluctuate every 24 h in mammals. These circadian rhythms are orchestrated by an autonomous central clock located in the suprachiasmatic nuclei that coordinates the timing of cellular clocks in tissues throughout the body. The critical role of this circadian system is emphasized by increasing evidence associating disruption of circadian rhythms with diverse pathologies. Accordingly, mounting evidence suggests a bidirectional relationship where disruption of rhythms by circadian misalignment may contribute to liver diseases while liver diseases alter the central clock and circadian rhythms in other tissues. Therefore, liver pathophysiology may broadly impact the circadian system and may provide a mechanistic framework for understanding and targeting metabolic diseases and adjust metabolic setpoints.

Keywords: Endocrine system and metabolic diseases; Hepatology; Metabolic syndrome; Metabolism; Obesity; Physiology

DOI: https://doi.org/10.1038/s44324-025-00058-1

Curr Biol. 2025 Apr 10. pii: S0960-9822(25)00375-6. [Epub ahead of print]

The adolescent circadian clock entrains to social time rather than sun time.

Rachel S Charoenthammanon, Joshua J Gooley.

The circadian timing of sleep is an important determinant of performance and health. There are opposing viewpoints, however, on whether light entrainment of the human circadian clock is mediated primarily by social time or solar time. Here, we provide evidence that adolescents' circadian clock entrains to their behavioral light-dark cycle determined by social demands. The circadian timing of sleep was compared between school and holiday periods in adolescents (n = 112) whose sleep was either constrained or unconstrained by early school start times. The circadian rhythm of melatonin (dim-light melatonin onset [DLMO]) closely tracked adolescents' earlier and shorter actigraphy-determined sleep pattern during the school week. The phase of entrainment from DLMO to sleep (darkness) midpoint was the same between holiday and school periods. As a consequence of obtaining short sleep on school nights, however, adolescents went to sleep later and woke up earlier relative to their melatonin onset. Hence, adolescents were "biologically ready" to go to bed earlier, and they likely woke up closer to the circadian minimum of alertness compared with their holiday sleep. Our results suggest that, in modern society, social constraints on sleep and associated light exposure (natural sunlight and electrical light) play an important role in entraining the circadian clock. Key strategies that may improve the duration and circadian timing of sleep in adolescents include advancing bedtimes, stabilizing sleep across weekdays and weekends, and delaying wake-up times by starting school later.

Keywords: adolescents; behavior; chronobiology; circadian; entrainment; light; melatonin; school; sleep; social

DOI: https://doi.org/10.1016/j.cub.2025.03.059