An international team including researchers from Newcastle University have studied the simplest natural circadian system found in blue green algae and reproduced its daily gene switching in the test tube.

Their study, published in Nature Structural and Molecular Biology, showed how the clock coordinates gene activity by switching off “morning” genes as “evening” genes turn on, and vice versa.

The importance of our circadian rhythms

The circadian clock is essential to our health and wellbeing, aligning our 24-hour biological cycles with the natural rhythm of light and darkness by switching genes on and off at precise time. When our internal clock falls out of sync with the external environment, it places a strain on both body and mind, something we experience acutely during jet lag or the transition to daylight-saving time. Some mental health issues are now known to be connected to unstable circadian rhythm.

Interest in circadian clocks is growing rapidly as their importance for health and medicine becomes increasingly clear. Medicines and vaccinations can be more effective when given at specific times of day, timed to match our circadian rhythms.

Circadian systems in complex organisms are intricate and challenging to study. To overcome this, the international research team including scientists from Newcastle University, turned to the simplest version of the circadian clock found in nature in cyanobacteria, tiny aquatic organisms that are also known as blue-green algae.

The team successfully recreated the daily rhythmic genetic switching process in a test tube and  using biochemical, structural and in vivo methods, they demonstrated how the clock coordinates gene activity by switching off “morning” genes as “evening” genes turn on, and vice versa, under laboratory conditions.

“We were able to show how a single signal from the clock can turn one set of genes on and another set off, generating opposite phases of gene expression. In that cell, that means some cellular processes are peaking at dusk and others at dawn,” said Professor Susan Golden, of the University of California San Diego, the senior author of the study.

Dr Yulia Yuzenkova, Senior Lecturer, Newcastle University’s Biosciences Institute said: "The most remarkable aspect is that the immense complexity and variability of cellular gene activity can be orchestrated into a beautiful rhythmic pattern by a clocking mechanism so simple. This research advances our understanding of biological rhythms and supports applications ranging from microbial biotechnology to human gut health.”

What the future holds

By understanding how circadian clocks control genes at the molecular level, scientists can clarify the mechanisms of the complex biological clock. They can also develop biological tools to biosynthesize target molecules at specific times of the day - in effect, scheduling tools that enable timed production of valuable compounds in biotechnology.

Looking further ahead, circadian biology may also offer new ways to regulate human gut microbiota, supporting wellbeing across multiple systems, including the brain.

REFERENCE: Mechanism and reconstitution of circadian transcription in cyanobacteria. Nature Structural and Molecular Biology. DOI: 10.1038/s41594-025-01740-0.