Our 24-hour, day-night cycles are kept by our circadian clocks. These internal timekeepers tell us when it’s time to eat and time to sleep. Now, researchers have successfully harvested a circadian clock from one bacterium species and transplanted it into another, endowing the recipient with a daily rhythm for the first time ever. The work was published in Science Advances this week.
Circadian clocks are found in many animals, plants, and even microbes, and they regulate various metabolic and behavioral changes using environmental cues, such as sunlight. Having to adjust the body’s circadian rhythm to match a travel destination’s day-night cycle, for example, results in jetlag. The cyanobacterium Synechococcus elongatus is photosynthetic, so they’re active in the day. Our famous gut microbe E. coli, on the other hand, is a noncircadian bacterium. They have no light receptors.
A Harvard team led by Pamela Silver reconstructed a Synechococcus elongatus circadian clock that can function by itself. These cyanobacterial internal clocks are composed of three proteins that are synchronized by light cues. When the bacterium is active during the day, the KaiA protein encourages the KaiC protein to bind to phosphate groups from the energy molecule ATP, New Scientist explains. At night, the KaiB protein antagonizes the activity of KaiA and encourages KaiC to let go of the phosphates.
The team transplanted that entire protein circuit into living E. coli. To help them see if the new clock was functioning properly, they linked the circuit to green fluorescent proteins that light up as the circadian oscillations are triggered. The E. coli glowed rhythmically for three days. This is sketched out in the diagram above.
A bioengineered circadian clock like this one could help fix disrupted circadian rhythms (including ours, as well as those of our gut microbiome). It could also be used to automate the delivery of cancer drugs, for example, which fluctuate in their efficacy based on when in the patient’s circadian cycle they were administered.
"The ultimate dream application would be to deliver these circadian E. coli to an individual in pill form, which could allow the circadian rhythm to be linked to additional biological circuits in order to perform a precisely-timed release of drugs, or to be able to sense and influence the host's circadian rhythm," first author Anna Chen of Harvard says in a news release.