The genetic switch the team inserted in E. coli came from lambda phage, a virus that commonly attacks this bacterium.
After invading E. coli, lambda typically lays low, living in a stealth mode called lysogeny in which its DNA simply hangs out in the E. coli's genome. But when the bacterium's DNA is damaged and only then the switch flips, instructing the virus to enter a mode called lysis in which it multiplies inside the cell and breaks through its membrane in a kind of microbial explosion.
"This is a very stable system in Nature," said lead author Jonathan Kotula, Ph.D., a Postdoctoral Fellow at HMS who is also affiliated with the Wyss Institute. "We knew the lambda switch would be a great candidate for the memory element, and we simply tweaked it to meet our needs."
The cells with the engineered lambda switch would not become lytic under any conditions. Kotula and the rest of Silver's team used standard molecular genetic tools to rig the switch such that it turned on only in the presence of an inactive form of the antibiotic tetracycline.
In laboratory experiments, the switch turned on within a few hours of exposure to the antibiotic and stayed in this 'ON' state inside E. coli for a week or more, even as the bacteria grew and divided. In short, the cells "remembered" that they had seen that molecule in the gut.
"It was truly shocking how cleanly the experiments worked," said Jordan Kerns, Ph.D., a Wyss Institute Postdoctoral Fellow.
But to function as a living diagnostic, the engineered
|Contact: Kristen Kusek|
Wyss Institute for Biologically Inspired Engineering at Harvard