"Science" assembles a biological clock in a test tube

In fact, the daily cycle of every aspect of our physiology is driven by the biological clock in the cell (also known as the circadian clock)

A team of scientists has now reconstructed the cyanobacteria's biological clock in test tubes, enabling them to study the rhythmic interactions of clock proteins in real time, and to understand how these interactions allow the clock to exert control over gene expression

Carrie Partch, professor of chemistry and biochemistry at the University of California, Santa Cruz and the corresponding author of the study, said: “Reconstructing a complex biological process, such as the circadian clock, from the ground up really helps us understand how circadian clock proteins work together.

Partch pointed out that from cyanobacteria to humans, the molecular details of the biological clock are very similar

"These results are very surprising, because it is common for the results observed in vitro to be somewhat inconsistent with the results observed in vivo

This new research builds on the previous work of Japanese researchers, who in 2005 reconstructed the cyanobacteria biological circadian oscillator, which is the basic 24-hour timing cycle of the clock

In addition to the oscillator protein, the new in vitro clock also includes two kinase proteins (SasA and CikA) whose activity is changed by interacting with the oscillator, as well as a DNA binding protein (RpaA) and its DNA target

"SasA and CikA activate and deactivate RpaA, respectively, to bind and deactivate DNA rhythmically," LiWang explained

Using fluorescent labeling technology, researchers can track the interactions between all these clock components, because the entire system is accompanied by circadian oscillations for many days or even weeks

The researchers also used an in vitro system to explore the genetic origin of clock interruption in a cyanobacteria strain with arrhythmia

"An amino acid change in a transcription factor can cause a cell to lose the rhythm of gene expression, even if its biological clock is intact," said co-author Susan Golden, director of the Circadian Biology Center at the University of California, San Diego

She added: "The real charm of this project lies in how teams from the three campuses of the University of California came together to discuss how to answer how a cell distinguishes time

Science

DOI

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