It’s not your typical clock. Rather than a quartz movement and sweeping second hand, the heart of this device is a colony of genetically engineered bacteria. A deceptively simple circuit of genes allows the microorganisms to keep time with synchronized pulses of fluorescent light, beating with a slow, rhythmic flicker of 50 to 100 minutes.
The bacteria represent the first synchronized genetic oscillator. Scientists say the tool will be foundational for synthetic biology, an offshoot of genetic engineering that attempts to create microorganisms designed to perform useful functions. The oscillator might one day provide the basis for new biosensors tuned to detect toxins, or for cellular drug delivery systems designed to release chemicals into the body at preprogrammed intervals.
Oscillators are an integral part of the biological world, defining cycles from heartbeats to brain waves to circadian rhythms. They also provide a vital control mechanism in electronic circuits. Biologists first set out to engineer a biological version more than a decade ago, creating a circuit dubbed the “repressilator.” (The creation of the repressilator, along with a genetic on-off switch, in 2000 is generally considered the birth of synthetic biology.) However, early oscillators lacked precision–the rhythm quickly decayed, and its frequency and amplitude couldn’t be controlled.
In 2008, Jeff Hasty and his team at the University of California, San Diego, created a more robust oscillator that could be tuned by the temperature at which the bacteria were grown, the nutrients they were fed, and specific chemical triggers. But the oscillations were still limited to individual cells–the bacteria did not flash together in time. In the new research, published today in the journal Nature, Hasty and colleagues build on this work by incorporating quorum-sensing, a molecular form of communication that many bacteria use to coordinate their activity.
The new oscillator consists of a simple circuit of two genes that creates both a positive and negative feedback loop. The circuit is activated by a signaling molecule, which triggers the production of both more of itself and of a glowing molecule called green fluorescent protein. The signaling molecule diffuses out of the cell and activates the circuit in neighboring bacteria.