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A Fast, Programmable Molecular Clock

The bacteria-based timepiece could be used as a biosensor for changing environmental conditions.
October 29, 2008

A molecular timepiece that ticks away the time with a flash of fluorescent protein could provide the basis for novel biosensors. The clock, or synthetic gene oscillator, is a feat of synthetic biology–a fledgling field in which researchers engineer novel biological “parts” into organisms.

UC San Diego bioengineers have created the first stable, fast, and programmable genetic clock that reliably keeps time by the blinking of fluorescent proteins inside E. coli cells. The clock’s blink rate changes when the temperature, energy source, or other environmental conditions change. Shown here is a microfluidic system capable of controlling the environmental conditions of the E. coli cells with great precision–one of the keys to this advance.
Credit: UC San Diego Jacobs School of Engineering

To create the clock, scientists genetically engineered a molecular oscillator composed of multiple gene promoters, which turn genes on in the presence of certain chemicals, and genes themselves, one of which codes for a fluorescent protein. When expressed in E. coli bacteria, the feedback system turns the fluorescent gene on and off at regular intervals.

The clock’s oscillations can be tuned by the temperature at which the E. coli are grown, the nutrients they are fed, and specific chemical triggers. According to a paper published today in Nature, the fastest oscillations that the scientists have recorded so far are about 13 minutes.

“The on-off frequency could potentially be used to determine the level of some toxic chemical in the environment,” says Jeff Hasty, a bioengineer at UC San Diego, who led the project. “One could make simple modifications so that it responded to other chemicals or sugars.”

According to a press release from UC San Diego,

One next step is to synchronize the clocks within large numbers of E. coli cells so that all the cells in a test tube would blink in unison. “This would start to look a lot like the makings of a fascinating environmental sensor,” said Jeff Hasty, a UC San Diego bioengineering professor and senior author on the Nature paper. Researchers in his lab have also developed sophisticated microfluidic systems capable of controlling environmental conditions of their E. coli cells with great precision. This enables the bioengineers to track exactly what environmental conditions affect their clocks’ blink rates.

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