Think of them as tiny environmental health officers. Bacteria have been engineered to monitor the state of a live animal鈥檚 gut. The work is a first step towards developing genetically modified bacteria that non-invasively diagnose problems such as gut infections or inflammation.
Synthetic biologists have made similar systems before in the lab, but never one designed to stand up to the harsh conditions in the gut of living mammals, says Jeffrey Way at Harvard Medical School. 鈥淣o one else has really quite had the courage to try,鈥� he says. 鈥淭here are a few examples, but for the most part people don鈥檛 quite have the confidence to put their engineered systems out into the real world鈥�.
Way was part of a team led by Pamela Silver, also at Harvard Medical School, that inserted genes from a virus into E. coli bacteria. Normally these genes make a protein called cI, but when the bacteria are exposed to a substance called anhydrotetracycline, they instead produce a protein called Cro.
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The team fed the bacteria to mice and collected faecal samples. Sure enough, only cI was detected unless the mice were given the chemical, in which case their faeces contained Cro proteins. The addition of the viral genetic switch meant the bacteria was effectively sensing and recording the chemical鈥檚 presence.
鈥淭his is a really exciting advance,鈥� say of MIT鈥檚 Synthetic Biology Center, who was not involved with the study. 鈥淭his is the first use of a genetic circuit in a real environment. It is remarkable that they were able to engineer the cells to perform a computational operation 鈥� albeit a simple one 鈥� in this environment.鈥�
Silver says it should be easy to engineer other genetic switches 鈥� ones that respond to telltale signs of inflammation, cancer, parasites or toxins in the gut, for example.
Programmable biobots
It might even be possible to engineer bacteria that deliver drugs if they detect disease. 鈥淵ou could think of them as little programmable robots that sense their environment and enact a therapeutic action when they discover a problem,鈥� says Voigt. Silver鈥檚 team are already thinking about ways to do this, and not just in the gut. 鈥淵ou could engineer skin bacteria to sense inflammation and have a very early form of a diagnostic and a therapeutic reaction,鈥� she says.
鈥淲e always want to figure out what鈥檚 going on in the dark recesses of our bowels,鈥� says , a microbiologist at the University of Michigan in Ann Arbor. 鈥淚t鈥檚 something people have been trying to do for a while.鈥�
鈥淚f [the modified bacteria] can tell that it鈥檚 right next to the evil bug, then crank out a specific antibiotic, that would be cool.鈥�
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