Bacteria that respond to red, green and blue light have produced some striking three-color artwork that's been making the rounds online, but the contribution they're making to the field of synthetic biology is even more impressive.
The artsy bacteria were engineered by Chris Voigt, professor of biological engineering at the Massachusetts Institute of Technology, and his team, who want to program cells to perform functions and also build materials from the bottom up.
"Cells are incredible atomic architects. They're able to build very precise materials you can't do with chemistry," Voigt says. "And you can do it in ambient conditions instead of using toxic solvents." They published their study this week in Nature Chemical Biology.
Engineered bacteria could be helpful to us in all sorts of ways. They could be designed to build tissue or materials, or identify disease in a patient and administer an exact dose of medicine to the right spot. They could swarm the roots of a plant in the soil and deliver a precise amount of fertilizer. They could produce iron particles as they grow, which could become components in electronics that are a hybrid of biology and machine.
A Boss System for Programming Cells
To realize that future, scientists have to get better at programming cells. That's where this latest technique, called an RGB system — for red, green and blue — comes in. It builds on more than a decade of research in Voigt's lab, in particular, a project he published in 2005, which described a way to get Escherichia coli bacteria to create black-and-white photos.
The 2005 black-and-white system consisted of four genes, 4,000 base pairs (the CG and AT bases in a double-stranded molecule), and three pieces of DNA called promoters that initiate the first action a gene takes to turn its instructions into a product, such as a protein.
Things have grown more complicated since then.
The team's RGB system consists of 18 genes, 14 promoters, as well as other bits of DNA called terminators and plasmids, and 46,198 base pairs.
"In one sense, it's going from one wavelength of light to three, but because you're doing that all inside the cell, it becomes exponentially difficult to get a lot things to work well, and that required a lot of technology," Voigt says.
The technology to program the cells included optogenetics (a way to control cells with light) a programming language for cells called Cello that Voigt and his team developed last year and a new method for controlling gene functions known as CRISPR.
Using these and other tools from synthetic biology, they designed a cell with the following parts:
- A sensor array made from phytochromes, the light receptors in plants
- A genetic circuit that processes the light signals
- A component called a resource allocator that links the circuit to an actuator responsible for producing a red, green or blue pigment
The cell could sense the three colors of light, process the information with the genetic circuits and, because the scientists were able to control what the genes did with the information — how they expressed it — the cells generated red, green, and blue pigment.
In a petri dish, the microbes "painted" a fruit still life, a geometric lizard motif and a leaping Super Mario.
Beyond Bacteria Art
Because the scientists are controlling gene expression, they could use the lights to do other things besides make art. In one test, the scientists controlled the cell's ability to produce acetate. Understanding the feedback system for acetate is critical for many industrial processes, such as making flavoring agents, solvents and fuels, where in some cases engineers may want the acetate but in other cases, they may not.
Voigt says that the RGB system also could be used to build molecules, a process that requires specific sets of reactions to occur at particular times. Turning the lights on and off at specific times could trigger metabolic pathways and enzymes at the right moment to make natural sweeteners and pharmaceuticals.
And because these cells are controlled by light, they could be controlled remotely.
For the next project, Voigt would like to build a larger, more complex system. But he and his team know that will be a challenge. It turns out that when they added a lot of genetic components to the cell, the otherwise nontoxic parts started to impede the cell's growth and in some cases, kill them.
"What is it about the design of the system that makes it difficult for the cell to function properly?" Voigt asks.
Finding the answer may involve some creativity.