bims-ciryme 2025-07-27 papers

Nat Commun. 2025 Jul 21. 16(1): 6686

Reconstitution of circadian clock in synthetic cells reveals principles of timekeeping.

Alexander Zhan Tu Li, Andy LiWang, Anand Bala Subramaniam.

The cyanobacterial circadian clock maintains remarkable precision and synchrony, even in cells with femtoliter volumes. Here, we reconstitute the KaiABC post-translational oscillator (PTO) in giant unilamellar vesicles (GUVs) to investigate underlying mechanisms of this fidelity. We show that our encapsulation methodology replicates native protein variability. With long-term, single-vesicle tracking of circadian rhythms using fluorescent KaiB and confocal microscopy, we find that oscillator fidelity decreases with lower protein levels and smaller vesicle sizes. KaiB membrane association, observed in cyanobacteria, was recapitulated in GUV membranes. A mathematical model incorporating protein stoichiometry limitations suggests that high expression of PTO components and associated regulators (CikA and SasA) buffers stochastic variations in protein levels. Additionally, while the transcription-translation feedback loop contributes minimally to overall fidelity, it is essential for maintaining phase synchrony. These findings demonstrate synthetic cells capable of autonomous circadian rhythms and highlight a generalizable strategy for dissecting emergent biological behavior using minimal systems.

DOI: https://doi.org/10.1038/s41467-025-61844-5

Sci Rep. 2025 Jul 19. 15(1): 26291

Chronic circadian disruption in adolescent mice impairs hippocampal memory disrupting gene expression oscillations.

Ines Gallego-Landin, Paula Berbegal-Sáez, Olga Valverde.

Chronodisruption, the misalignment of internal biological systems with external environmental changes, negatively impacts health and cognition. A prevalent form, social jet lag, affects a large portion of adolescents and is associated with reduced academic performance, and impaired emotional regulation. Despite its prevalence, the mechanism by which adolescent chronodisruption results in cognitive deficits remains unexplored. Here, we induced chronic chronodisruption in adolescent mice through light/dark cycle manipulation. We performed a battery of established behavioral tests alongside an analysis of daily rhythms of expression of genes involved in relevant physiological functions. We report that adolescent circadian disruption induces impairments in short-term, social, and spatial memory without prompting anxiety-like behavior. Gene expression analyses revealed altered oscillation patterns of circadian clock genes in the hypothalamus and hippocampus. Furthermore, we identified alterations in daily patterns of genes involved in glucocorticoid and endocannabinoid transmissions as well as synaptic plasticity. This work emphasizes the importance of circadian homeostasis for cognitive function and hippocampal homeostasis. Thus, understanding the mechanism underlying adolescent chronodisruption is essential to better understand its long-term implications for cognitive function and overall health.

Keywords: Adolescence; Behavior; Chronodisruption; Endocannabinoids; Gene expression; Memory impairments; Social jet lag

DOI: https://doi.org/10.1038/s41598-025-12237-7

Sci Rep. 2025 Jul 23. 15(1): 26709

Morning clock gene expression in young adults of early and late chronotypes.

Bettina Krueger, Luisa Sophie Rajcsanyi, Katharina Hundertmark, Bianca Stutz, Anke Hinney, Anette Buyken.

Variations in circadian rhythm-related genes influence the individual chronotype. Here, we hypothesize that the peak of clock gene expression at 7 a.m. differs between young adults with a late chronotype and young adults with an early chronotype. Participants of the Chronotype and Nutrition nutritional trial (ChroNu study) were selected for their chronotype assessed by the Munich Chronotype questionnaire (MCTQ) and actigraphy. Total RNA was isolated from CD14+ monocytes of participants at 7 a.m. on the run-in day. Expression levels of seven clock genes (PER1, PER2, PER3, NR1D1, NR1D2, CRY1 and CRISPLD2) of individuals with early (n = 11) or late chronotypes (n = 19) were analysed by reverse transcription quantitative polymerase chain reaction. Difference in expression levels was tested by Mann Whitney-U test. The relative expression levels of the selected genes were not significantly different between individuals with early and late chronotypes (all p > 0.07). Contrary to expectation, clock gene expression levels at 7 a.m. was similar in individuals with early and late chronotypes. Further studies on larger sample sizes with multiple sampling time points should elucidate whether gene expression is altered at other day times underscoring the biological difference between individuals with early or late chronotypes.

Keywords: Chronotype; Clock genes; Expression level; Young adults

DOI: https://doi.org/10.1038/s41598-025-12423-7