Stories of unusual and remarkable transplants seem to happen every day. Years back, news of organ transplants, including the heart and liver, made the headlines, while today we are hearing about face transplants, skull transplants, penis transplants, and now… circadian rhythm transplants? After harnessing the ‘body clock’ mechanism found in cyanobacteria, Harvard scientists transplanted it into a common species of bacteria that is naturally non-circadian.

This is how it worked: a team of researchers led by the synthetic biologist Dr. Pamela Silver studied the cyanobacteria, a photosynthetic species that is the only bacteria known to naturally contain a circadian rhythm. Circadian rhythms — the gentle oscillations which have been observed in plants, animals, and humans — regulate many aspects of an organism’s physiological, behavioral, and metabolic functions.

“We think like engineers to manipulate and use biological circuits in a predictable, programmable way,” Silver, who is a professor in the department of systems biology at Harvard Medical School, stated in a press release. Essentially, she and her team look at any natural system as a simple module that might be disconnected, moved around, and reconnected, just as you would a computer keyboard, say, or speakers.

Plug And Play

In this case, the team examined the cyanobacteria and removed the protein circuit responsible for regulating its circadian oscillations. Next, they transplanted the protein circuit into another bacterial species, E. coli. Because it is so well understood and easy to genetically alter, this species is widely used by biologists. This transplant procedure, needless to say, was not simple. It involved connecting the protein circuit to various gene expression components as a way to influence the metabolic and behavioral functions of the E. coli bacteria in relation to the day-night cycle.

Specifically, in the experimental E. coli, the mechanism was linked to fluorescent proteins that lit up each time the circadian oscillations were triggered, causing the E. coli to glow rhythmically.

And so an exquisite visual confirmation confirmed the transplant’s success.

“The ultimate dream application would be to deliver these circadian E. coli to an individual in pill form,” said Anna Chen, first author of the study and a systems biology graduate student at the Wyss Institute and Harvard Medical School. This application, she explained, “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.”

In particular, the scientists imagine using similarly modified and genetically engineered circadian E. coli to monitor our gut microbiota, the bacteria which reside in our gastrointestinal tracts and influence our health.