Jet lag is common these days. Flying across several time zones within hours makes the body’s natural clock go out of sync. This natural body clock is called the circadian clock. Circadian means ‘about a day’ in Latin. This circadian clock helps all organisms to maintain their metabolism and other bodily functions based on the light-dark circle, i.e. day-night cycle around them. The circadian clock follows a 24-hour cycle and is adjusted based on the external visual cues. So it is not always exactly 24 hours long.

Transplanting the Circadian Clock

Image courtesy of Anna H. Chen

Each organism’s circadian rhythm is unique and is subject to what the specific organism is exposed to. But changing the circadian rhythms of an organism can prove to be very useful. Though jet lag is one everyday example, there are several areas where it is very profitable as it stands to increase the productivity. As the circadian clock is regulated by the interaction of several proteins and biomolecules, it is possible to change the clock by tinkering with related molecules.

At the Wyss Institute for Biologically Inspired Engineering at Harvard, Synthetic biologist Pamela Silver, PhD, and her team have published their exciting new results. Silver’s team has now made it possible for transplanting the circadian clock from one microorganism with a circadian clock into another without a circadian clock. Though the team worked on this out of curiosity, the team’s work has opened the gates to several potential applications for engineered cells that exhibit diurnal rhythms i.e. a daily bodily process regulation.

Synthetic organisms can be designed for medical drug production and/or secretion at particular time(s) of each day. Not just for medicines, but this could be extremely helpful in energy harvesting, fuel storage, etc. By adjusting their circadian rhythms, humanity stands to gain a lot.

Silver’s team successfully reconstructed the circadian clock machinery from cyanobacteria (a type of photosynthesising bacteria and the only bacteria known to have diurnal cycles naturally) inside Escherichia coli (a type of bacteria usually found in the lower intestines of warm blooded organisms). Escherichia coli or E. coli do not have a natural circadian clock.

Three proteins—KaiA, KaiB, and KaiC—make up the circadian clock in cyanobacteria. While KaiC is phosphorylated with the assistance of KaiA during the day; KaiC is dephosphorylated in the night as KaiB antagonizes KaiA. Simply put, KaiC is activated by KaiA during the day while KaiB prevents this activation during the night. This process is even possible in a test tube. Phosphorylated i.e. activated KaiC interacts with SasA, a protein. Silver’s team engineered KaiC and SasA inside the E. coli such that, upon interaction of these two proteins, would initiate the transcription (and hence production through translation) of a fluorescent reporter protein. The fluorescent protein acts as the indicator of the success of the process.

The team observed that the synchronicity of the clock in E. coli is lost within the first three days. But the team is excited about the fact that the experiment proves that transplanting the circadian clock into a different organism is possible.

Journal reference: Anna H. Chen, David Lubkowicz, Vivian Yeong, Roger L. Chang, and Pamela A. Silver. Transplantability of a Circadian Clock to a Noncircadian Organism. Science Advances, 2015 DOI: 10.1126/sciadv.1500358