Harvard team transplants circadian wiring, pointing to new drug applications

Harvard's Pamela Silver

Harvard synthetic biologist Pamela Silver has led a successful effort to transplant the "wiring" used for circadian rhythm into a common species of bacteria, a process that could one day help regulate the body's natural rhythm or even aid in drug delivery and development.

The group of scientists took the protein circuit used to regulate circadian oscillations out of a photosynthetic bacteria species and then transplanted it into E. coli. That could then be linked to "additional gene expression components to potentially influence metabolic and behavioral functions in programmable relation to the day-night cycle."

If you can influence metabolism, researchers added by way of illustrating potential applications, then you can target obesity or glucose resistance. You might also be able to use this approach to influence the way the body responds to drugs, interfering with the natural ebb and flow, for example, in response to oncology drugs. Or you might use the transplanted circadian wiring in a new therapy that resets the body's clock, overcoming jet lag.

In this case, the wiring was tied to fluorescent proteins that caused the E. coli to glow each time it was triggered--demonstrating that they had successfully completed the transplant.

"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," said the study's first author, Anna Chen, a systems biology graduate student at the Wyss Institute and Harvard Medical School.

"What's really amazing is that we've demonstrated the modularity of biological systems--this finding goes beyond the transplantability of a circadian rhythm to open new doors to understanding how other modular biological circuits could be transplanted from one species to another," said Silver.

- here's the release