In 2008, researchers from the University of California, San Diego (UCSD) created a stir with their blinking genetic clock, which had the ability to keep track of time by turning on and off the genes in a bacterial cell that express fluorescent protein. Now, they have taken their clock one step further by developing a method to make the bacteria fluoresce in unison in reaction to environmental changes.
The new method was developed by the same researchers who made the original genetic clock: Jeff Hasty, associate professor of biology and bioengineering at UCSD; Lev Tsimring, associate director of UCSD’s BioCircuits Institute; and UCSD bioengineering graduate students Tal Danino and Octavio Mondragon-Palomino. Their improved approach utilizes quorum sensing to synchronize the fluorescence of Escherichia coli bacteria.
“Many bacteria species are known to communicate by a mechanism known as quorum sensing, that is, relaying between them small molecules to trigger various behaviors,” said Hasty in a press release. “Other bacteria are known to disrupt this communication mechanism by degrading these relay molecules.”
The researchers designed a network in E. coli cells with positive and negative feedback components to grow a colony of synchronized genetic clocks. Hasty said the architecture of the new clocks is similar to their previous clock, but the addition of quorum sensing allows the oscillations among the bacterial cells to be relayed from cell to cell. This enables the bacteria of the new clocks to fluoresce on and off in unison in response to environmental changes.
“The use of quorum sensing is a promising approach to increase the sensitivity and robustness of the dynamic response to external signals,” said Hasty. “In nature, synchronization typically helps stabilize a desired behavior arising from a network of intrinsically noisy and unreliable elements. We think the synchronized genetic clock sets the stage for the use of microbes as a macroscopic biosensor with oscillatory output, or applications of using a synchronized periodic signal in drug delivery.”
The researchers developed devices to control the sizes of the bacterial colony on both a micron scale and a millimeter scale. At the micron scale, the researchers reported the bacterial cells can oscillate in unison from 50 to 90 minutes, a time period that can be tuned externally. At the larger millimeter scale, the researchers were able to actually see the signal relayed through the colony. This makes the exact time the signal is deployed incredibly important.
“Synchronization plays a crucial role in physics and biology as a way of self-organization of highly regular behavior with less-than-perfect components,” said Tsimring in the press release. “This phenomenon has a myriad of applications in modern technology, from communication networks to GPS. Our study demonstrates how inherently noisy gene oscillators can operate together with beautiful synchronicity and regularity once coupled together in a specific way."
This improvement on the genetic clock could help scientists develop bacteria-based genetic sensors with the ability to assess changes in temperature, poisons, and other environmental hazards. “Programming living cells is one defining goal of the new field of synthetic biology,” said Hasty.
The scientists received funding for their improved genetic clock from the National Institute of General Medical Sciences. The paper, “A synchronized quorum of genetic clocks” was published Jan. 21 online in Nature.