Rice University bioengineers have created a toolkit that uses colored lights and engineered bacteria to bring both mathematical predictability and cut-and-paste simplicity to the world of genetic circuit design.
“Life is controlled by DNA-based circuits, and these are similar to the circuits found in electronic devices like smartphones and computers,” said Rice bioengineer Jeffrey Tabor, the lead researcher on the project.
“A major difference is that electrical engineers measure the signals flowing into and out of electronic circuits as voltage, whereas bioengineers measure genetic circuit signals as genes turning on and off.”
In a paper appearing online in the journal Nature Methods, Tabor and colleagues, including graduate student and lead author Evan Olson, describe a new, ultra high-precision method for creating and measuring gene expression signals in bacteria by combining light-sensing proteins from photosynthetic algae with a simple array of red and green LED lights and standard fluorescent reporter genes.
By varying the timing and intensity of the lights, the researchers were able to control exactly when and how much different genes were expressed. “Light provides us a powerful new method for reliably measuring genetic circuit activity,” said Tabor, an assistant professor of bioengineering who also teaches in Rice’s Ph.D. program in systems, synthetic and physical biology.
“Our work was inspired by the methods that are used to study electronic circuits. Electrical engineers have tools likeoscilloscopes and function generators that allow them to measure how voltage signals flow through electrical circuits. Those measurements are essential for making multiple circuits work together properly, so that more complex devices can be built. We have used our light-based tools as a biological function generator and oscilloscope in order to similarly analyze genetic circuits.”
If a gene is not “expressed,” it is turned off, and its product is not produced. The bacteria used in Tabor’s study have about 4,000 genes, while humans have about 20,000. The processes of life are coordinated by different combinations and timings of genes turning on and off.
Each component of a genetic circuit acts on the input it receives — which may be one or more gene-expression products from other components — and produces its own gene-expression product as an output.
By linking the right genetic components together, synthetic biologists like Tabor and his students construct genetic circuits that program cells to carry out complex functions, such as counting, having memory, growing into tissues, or diagnosing the signatures of disease in the body.