If the planet Vulcan had microbes, they might look something like this. Scientists have engineered bacteria that can perform four basic operations of logic: AND, OR, NAND and NOR.
By combining these logic units in various ways, it could be possible to engineer microbes with an internal “decision tree” logic that controls their behaviors. The technique, which is described in the Oct. 17 Science, could give scientists a new level of control when designing microbes for a variety of uses, such as fermenting biofuels or producing pharmaceuticals.
“It’s the first installation of logic gates for controlling gene expression in a living cell,” comments Kensaku Sakamoto, an expert in DNA computation at RIKEN Systems and StructuralBiologyCenter in Yokohama, Japan. “It’s a wonderful result, and a milestone in the efforts for artificial regulation of living systems.”
Christina Smolke and Maung Nyan Win of the California Institute of Technology in Pasadena added custom-designed snippets of DNA to the tail end of a gene, and then inserted that gene into either E. coli bacteria or cells of brewer’s yeast. When the cells transcribed the DNA into molecules of RNA — the first step toward making functional proteins — the snippets of code knotted up into 3-dimensional twists in the RNA. These twists can sense the presence of certain “input” molecules and respond by either destroying the RNA or leaving it intact.
If the RNA is left intact, it will produce the protein it encodes; if not, it won’t. It’s like a binary switch in a computer.
Each twist in the RNA can be designed independently of the other twists, and combining them in various ways can make the self-destruct switch respond to different logical combinations of the input molecules.
In the experiments, Smolke’s team used only two kinds of input molecules — tetracycline and theophylline. For an AND gate, both of these molecules had to bind to the RNA switch to keep the RNA intact, thus allowing it to produce green fluorescent protein as an “output.” For an OR gate, either input molecule was enough to achieve the same result. If the green protein was produced, it represented a “true” result, while no production of the protein represented “false.”
“They’ve been able to string these things together to make them do more complex things,” comments Jeffrey Poet, a mathematician at MissouriWesternStateUniversity in Joseph, who has designed other ways for cells to perform computations.
The modular design of these RNA-based logic computations could eventually enable engineering logic circuits into these microbes with the kind of control engineers have over logic circuits in silicon chips, Smolke suggests.