Scientists Built a Cell That Can Keep Time Like a 24-Hour Clock

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Our biological clock, or circadian rhythm, is immensely important to our health, and scientists are now unpacking the process’s secrets at the cellular level.
Researchers successfully created synthetic, cell-like structures, or vesicles, to test how varying concentrations of so-called “clock proteins” affect the vesicles’ natural timekeeping.
The team—amongst other discoveries—found that clock accuracy was proportional to both the amount of clock proteins and vesicle size.

One of the many biological wonders of life on Earth is the near-perfect ways our bodies can sense the passage of time. Known as our biological clock or circadian rhythm, this natural process regulates our wake-sleep cycle and is highly attuned to Earth’s 24-hour rotation.

To better understand this mechanism, scientists from University of California Merced attempted to reconstruct this clockwork system in cyanobacteria. The team created cell-like structures known as vesicles (each only 2 to 10 micrometers in diameter) and loaded them with “clock proteins”—groups of proteins that play an important role in regulating the circadian rhythm. The results were published this week in the journal Nature Communications.

In this study, the authors used cyanobacterial clock proteins KaiA, KaiB, and KaiC. As Earth.com describes, KaiC acted as the system’s hub while the other proteins shifted the process forward and backward. The team then inserted the vesicle lipid with a fluorescent tag whose steady glow showed the circadian rhythm in action, and found that both vesicle size and the amount of “clock proteins” were proportional to how well the vesicles could keep time.

“This study shows that we can dissect and understand the core principles of biological timekeeping using simplified, synthetic systems,” Anand Bala Subramaniam from UC Merced, one of the lead authors on the study, said in a press statement.

When the proteins were reduced, however, the vesicles were no longer accurate timekeepers. The authors were able to reliably reproduce this gradual loss of timekeeping, and by building computational models of the vesicle population, the scientists also discerned that the circadian rhythm’s additional role of turning genes on and off—in order to control physiological and behavioral processes—did not interfere with this timekeeping ability on the individual level, but proved essential for synching clocks across the population.

“This new study introduces a method to observe reconstituted clock reactions within size-adjustable vesicles that mimic cellular dimensions,” Mingxu Fang, a microbiologist from Ohio State University who wasn’t involved with the study, said in a press statement. “This powerful tool enables direct testing of how and why organisms with different cell sizes may adopt distinct timing strategies, thereby deepening our understanding of biological timekeeping mechanisms across life forms.”

Understanding the ins and outs of circadian rhythm is immensely important, as the biological process—or the disruption of it—can lead to a variety of illnesses, including cardiovascular disorders and cancer. It can also impact the treatments for these diseases, and scientists have even explored a concept known as “chronochemotherapy” to increase the efficacy of the drugs while limiting toxicity by carefully timing doses.

The 24-hour clocks within our cells are the smallest on Earth, but they also might be the most important.

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