Synthetic biology“Kill switches” shut down engineered bacteria
Many research teams are developing genetically modified bacteria that could one day travel around parts of the human body, diagnosing and even treating infection. Before such bacteria can be safely let loose, however, scientists will need to find a way to prevent them from escaping into the wider environment, where they might grow and cause harm. To this end, researchers have developed safeguards in the form of two so-called “kill switches,” which can cause the synthetic bacteria to die without the presence of certain chemicals. This synthetic biology technique could make it safer to put engineered microbes to work outside the lab.
Many research teams are developing genetically modified bacteria that could one day travel around parts of the human body, diagnosing and even treating infection. The bugs could also be used to monitor toxins in rivers or to improve crop fertilization.
However, before such bacteria can be safely let loose, scientists will need to find a way to prevent them from escaping into the wider environment, where they might grow and cause harm.
To this end, researchers at MIT, the Broad Institute of MIT and Harvard, and the Wyss Institute at Harvard University have developed safeguards in the form of two so-called “kill switches,” which can cause the synthetic bacteria to die without the presence of certain chemicals.
In a paper published in the journal Nature Chemical Biology, the researchers describe their two kill switches, which they call “Deadman” and “Passcode.”
Stand-alone circuits
There have been a number of attempts to develop kill switches over the past year, according to James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Department of Biological Engineering and Institute for Medical Engineering and Science (IMES), who led the research.
These include efforts to reprogram the entire genome of the organism to ensure that it requires the presence of certain amino acids or other chemicals in order to survive, divide, and grow.
However, this approach can be both labor- and resource-intensive, and could introduce changes that might make the organism less useful as a monitoring or diagnostic tool, Collins says.
“In our case, we are introducing standalone circuits that can be popped in to any number of different organisms, without needing to rewire or change much of the genome in order for it to accommodate the switch,” he says.
The Deadman switch, for example, is part of a bacterial strain that needs an external chemical to prevent a continuously expressed toxin from killing the cell.
The switch was motivated by the so-called deadman brakes on old trains, which required a conductor to be in constant contact with the handle or pedal in order for the vehicle to move forwards, Collins says.
The system, which builds on previous work in Collin’s lab, consists of a genetic “toggle” switch made up of two transcription factor genes.
