A team of engineers from MIT has created genetic circuits in bacterial cells that can not only perform logic functions, but also remember the results. These functions can then be encoded within the cell’s DNA and can be passed on in other cells for dozens of generations. The research, which was outlined in the Feb. 10 online edition of Nature Biotechnology, states that this breakthrough could allow for more efficient controls in biomanufacturing, as well as the programming of stem cells into other cell types.
In a statement, Timothy Lu, an MIT assistant professor of electrical engineering and computer science and biological engineering and senior author of the Nature Biotechnology paper said: “Almost all of the previous work in synthetic biology that we’re aware of has either focused on logic components or on memory modules that just encode memory. We think complex computation will involve combining both logic and memory, and that’s why we built this particular framework to do so.”
Normally, synthetic biologists use interchangeable genetic parts to design circuits that perform a specific function, such as detecting a chemical in the environment. In that type of circuit, the target chemical would generate a specific response. However Lu and his colleagues set out to design a circuit that would be irreversibly altered by the original stimulus, creating a permanent memory of the event. To do this, they used circuits depend on enzymes known as recombinases, which can cut out stretches of DNA, flip them, or insert them. Sequential activation of those enzymes then allows the circuits to count events happening inside a cell.
“It’s really easy to swap things in and out,” says Lu, who is also a member of MIT’s Synthetic Biology Center. “If you start off with a standard parts library, you can use a one-step reaction to assemble any kind of function that you want.”
The research also has green potential as it would offer better control over the production of cells that generate biofuels as well as drugs or other useful compounds. Instead of creating circuits that are always on, or using promoters that need continuous inputs to control their output levels, scientists could transiently program the circuit to produce at a certain level. The cells and their progeny would always remember that level, without needing any more information.
According to Michael Jewett, an assistant professor of chemical and biological engineering at Northwestern University, the new design represents a “huge advancement in DNA-encoded memory storage.”
“I anticipate that the innovations reported here will help to inspire larger synthetic biology efforts that push the limits of engineered biological systems,” Jewett added.
Images: MIT and USDAgov