Scientists have engineered bacteria that can communicate with each other in a synchronized manner, lighting up in waves of fluorescent green, according to report in this week's Nature. The advance paves the way for developing environmental sensors and drug delivery systems that can time the release of medicines in periodic bursts.
A supernova burst in a colony of coupled genetic clocks after critical cell density Image: Tal Danino, Octavio Mondragon- Palamino, Lev Tsimring
"I think [the study] represents the state of the art of our ability to create synthetic gene networks," said James Collins of Boston University. "It was really brilliant that they were able to pull it off."
Jeff Hasty and colleagues at the University of California, San Diego, engineered a very simple positive feedback loop using just two genes, plus the green fluorescent protein gene as a reporter. "The beauty of this thing is its simplicity," said Hasty. One gene, luxI, produces a molecule called AHL that can diffuse to neighboring cells to activate the luxI promoter. The promoter drives the production of lux1 (plus GFP), as well as a downstream gene coding for the protein AiiA , which degrades AHL. When the cells of the engineered E. coli culture grow to a high enough concentration, producing enough AHL to drive the promoter, GFP expression kicks in with a flash of fluorescence. The light is quickly dimmed, though, as AiiA expression increases. "It's a coupled positive and negative feedback," said Hasty.
The key to having the cells interact in unison is that "only at a certain [cell]density do you get oscillation," said Hasty -- a detail that surprised the investigators when they initially ran the experiment. After first author Tal Danino had loaded the engineered bacteria onto the microfluidics chip that controlled their density and the flow of culture media, he watched for a few hours and then left for the night, letting the video camera capture the E.coli at work. The next morning, the bacteria were still dark. "I assumed it hadn't worked," said Danino. But when he looked back over the footage, he saw the first burst, and then a second, followed by a burst consistently every hour afterwards.
Researchers had previously developed bacteria in which gene expression oscillates, but to date, no one could get cells to oscillate in unison as a population.
There's a lot that can be done with a system that oscillates in synchrony, said Collins, who engineered and published the first bacterial toggle switch 10 years ago. "This creates a platform for a biomolecular drug delivery system that could deliver therapeutic proteins in a periodic fashion" -- for example, on a schedule that matches or complements natural circadian cycles, he said. Bacteria could be engineered to release a particular therapeutic drug, with the entire colony being introduced into a patient's normal microbiota, Collins envisioned. Another potential application of the technology would be in the detection and remediation of environmental toxins.
The engineered cells also offer a new model system for studying emergent systems, or how complex properties -- such as synchronized oscillation -- arise from simpler starting materials -- a two genes network. (See our feature on studying complexity and emergent systems here).
But it may be a while before the potential of this system is realized, said Hasty. "The field is still cutting its teeth on how to build basic circuits."
Correction (Feb 20th 2010): The original version of this article misspelled Tal Danino's name. The Scientist regrets the error.
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