Could GM bugs act as an early warning system for disease?
Think of them as tiny environmental health officers. Bacteria have been engineered to monitor the state of a live animal’s 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. “No one else has really quite had the courage to try,” he says. “There are a few examples, but for the most part people don’t quite have the confidence to put their engineered systems out into the real world”.
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.
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’s presence.
“This is a really exciting advance,” say Chris Voigt of MIT’s Synthetic Biology Center, who was not involved with the study. “This 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 – albeit a simple one – in this environment.”
Silver says it should be easy to engineer other genetic switches – ones that respond to telltale signs of inflammation, cancer, parasites or toxins in the gut, for example.
It might even be possible to engineer bacteria that deliver drugs if they detect disease. “You could think of them as little programmable robots that sense their environment and enact a therapeutic action when they discover a problem,” says Voigt. Silver’s team are already thinking about ways to do this, and not just in the gut. “You could engineer skin bacteria to sense inflammation and have a very early form of a diagnostic and a therapeutic reaction,” she says.
“We always want to figure out what’s going on in the dark recesses of our bowels,” says Vincent Young, a microbiologist at the University of Michigan in Ann Arbor. “It’s something people have been trying to do for a while.”
“If [the modified bacteria] can tell that it’s right next to the evil bug, then crank out a specific antibiotic, that would be cool.”