Can you imagine downloading mini computer programs that could monitor your blood sugar levels, watch for cholesterol buildups, and destroy tumor cells? These are some of the ultimate goals of researchers who are busy designing genetic circuits. Instead of using silicon, they use DNA, the genetic material of all living things, to create intricate networks inside of a cell that do something specific.
“We build a circuit by getting pieces of DNA and interconnecting them,” says Dr. Stephen W. Davies, an assistant professor at the Institute for Biomaterials and Biomedical Engineering at U of T.
Just as electrical engineers wire digital on-off switches of silicon chips into complicated circuits, researchers like Davies cut and paste together pieces of DNA to build different genetic circuits that perform different tasks, such as doing a measurement or storing information. He calls them “baby computers.”
Seema Nagaraj, a graduate student working in Davies’s lab, opens a fridge to show a bunch of petri dishes containing E. coli bacteria. Bacterial cells are much simpler than human cells, making them easier to use in research. They serve as the power supply for Davies’ genetic circuit, which is “inserted” into the bacteria’s DNA. There are molecules inside these cells that can bind to “control sites.” A control site is a region of DNA that does not code for a protein (like a gene does), but controls how much a certain gene is translated into its corresponding protein. Molecules that bind to these control sites can thereby direct protein production, increasing or decreasing how much a certain gene is translated, and thus controlling the levels of a certain protein inside a cell.
One of the difficulties of building genetic circuits is that circuits are not always inserted properly, Nagaraj explains, because of random fluctuations in the levels of various molecules inside a living cell. This can prevent the process from happening like scientists want it to.
But there are times when fluctuations may actually be important, Davies says, particularly when we could use them to control the activity of viruses. Viruses are not like cells, and it is debatable whether they are even alive-they simply contain a small amount of DNA surrounded by some sort of protective protein coat. Viruses must go through a stage when they incorporate themselves inside of cells in order to reproduce. They use the host cell’s machinery to replicate more viruses. Many viruses have a genetic switch that enables them to go from a dormant stage to an active one once they are inside of a cell.
But certain molecules inside the host cell can repress this activation process. Understanding how these levels fluctuate in the cell becomes very important. If researchers could one day manipulate the fluctuations of such molecules in order to control the development of viruses, they could potentially cure many fatal diseases.
“Now wouldn’t that be cool,” says Davies, “if we could say, ‘hey we can add this artificial genetic circuit [into our cells] to turn a virus off forever,’ that would be good.”
