What if our cells could be programmed to detect an imminent heart attack and warn us in time to get to the doctor before it happens? Or perhaps they could sense falling blood sugar in diabetics and signal an electronic device to administer insulin?
That’s the dream of biologists at the Massachusetts Institute of Technology (MIT). They’ve created synthetic biology “circuits” that could someday be used for those purposes and more, they reported in Science.
The circuits rely on protein-protein interactions, naturally occurring processes in which one protein in the body switches another on or off by either adding or deleting chemicals known as phosphates. They engineered a way to quickly activate the circuits, they said.
The inspiration for the circuits came from protein-protein interactions that are “bistable,” meaning they can toggle back and forth between two different stable states. In the body, bistable switches govern several important functions, including activating immune cells and forming memory.
The MIT team started with 14 proteins from a variety of species, including plants and people. They engineered the proteins so they could regulate each other in a yeast host, producing a signal in response to an event. For this study, the event was exposure to sorbitol, a sugar that’s common in fruits.
The researchers showed that they could design a synthetic circuit that prompted cells to store a memory of sorbitol exposure, display it as a fluorescent protein and then pass the memory to descendent cells. They also designed a circuit in which cells stopped dividing once they detected sorbitol.
The researchers were able to trigger the signals in one second, they reported. Other synthetic circuits, by contrast, can take hours or days to produce results, they said.
So how could this be used in medicine? The circuits could be programmed to detect drug overdoses, abnormal hormone levels, falling blood sugar and many other signs of trouble in the body, said senior author Ron Weiss, Ph.D., a professor of biological engineering and of electrical engineering and computer science at MIT, in a statement. “You could have a situation where the cell reports that information to an electronic device that would alert the patient or the doctor, and the electronic device could also have reservoirs of chemicals that could counteract a shock to the system," he said.
Most efforts to design synthetic biology circuits to date have relied on the transcription of genes within cells that can respond to certain inputs. This approach is being pursued in a range of diseases, including cancer. Problem is, it takes time for genes to be transcribed and then produce proteins.
The speed by which MIT’s newly created circuits work could enhance their utility, Weiss said. The researchers hope to use the circuits to develop pollution sensors and diagnostics.
"That switch to extremely fast speeds is going to be really important moving forward in synthetic biology and expanding the type of applications that are possible," Weiss said.