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Circadian clock made from scratch to probe how biological rhythms work

Circadian clocks help living things keep time, and one has now been assembled from scratch in the lab to find out more about how they work
Bacteria circadian clock protein molecule
Computer model showing the molecular structure of a circadian clock Kai protein found in cyanobacteria
LAGUNA DESIGN/SCIENCE PHOTO LIBRARY

A circadian clock has been recreated in full inside a test tube. It is the first time the cellular pacemaker has been produced outside a living organism.

The clock, copied from a cyanobacteria, was devised by at the University of California, Santa Cruz, and her colleagues. It is made from six proteins and can work without any human intervention for several days. “I think the record we’ve got so far is two weeks,” says Partch.

Circadian clocks regulate the timing of the activity of an organism’s various cellular systems. In cyanobacteria, they usually work on a 24-hour light cycle.

“By forming this clock outside of a living organism, we can more closely analyse certain aspects of the process,” says Partch.

The team was also able to monitor the rhythms within the cyanobacteria, by fluorescently tagging the proteins to get real-time data on their timekeeping.

Using this method and by adding mutations to the test-tube system that turned off certain parts of the clock, the researchers discovered that two of the proteins, called SasA and KaiB, are far more influential than previously thought.

“We’d previously believed that SasA was just an amplifier of the clock – it kept everything robust,” says Partch. “But in this study, we found that this function is largely dispensable and, in fact, its main function is to recruit one of the clock’s core proteins, KaiB.”

The team wouldn’t have been able to discover this by just looking at the clock in a living organism, she says.

The next step is to determine how the clock trains itself to the 24-hour cycle in the first place, says Partch.

“This is cool because they’ve managed to extend the in-vitro cyanobacteria clock to include effects on transcriptional output [which affects gene expression],” says at the University of Pennsylvania, noting that the clocks of more complex organisms like humans work via this system too.

Science

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Topics: Sleep