The new sensor can detect four different molecules, and may be a breakthrough that allows precise environmental monitoring by cells.
Researchers at the Massachusetts Institute of Technology (MIT) have created a complex cellular circuit that uses genes as interchangable parts. Previously, attempts to create synthetic networks — used for functions including monitoring environmental conditions — have been hampered due to the difficulty of assembling genetic parts that don’t interfere with each other.
Unlike electronic circuits, biological alternatives cannot be isolated from each other, and so the difficulty remains: how do you keep proteins that control one area distinct from other parts of a cell?
Described in the journal Nature, Christopher Voigt, co-director of the Synthetic Biology Center at MIT, and his team have been able to integrate a complex sensor system for different molecules into cells.
In a process described by the professor as “incredibly complex, stitching together all these pieces”, by studying bacteria that causes salmonella, the scientists were able to successfully isolate genetic circuits from one another.
Salmonella has a tightly-regulated celluar pathway, used to control the injection of proteins into human cells. Made of an activator, promoter — DNA where proteins bind to initiate transcription of a gene — and a chaperone protein, this regimental type of pathway became a strong case study for the team, although an additional 60 systems were investigated.
The key elements are the protein inputs and outputs of a cell — the activators and chaperones. Without regulation, creating biological sensors would be far less effective than standard electrical circuits. After rounds of trial-and-error to mutate and screen manipulated genes, the scientists were able to create thousands of variants — some becoming ‘optimal’ and controllable within a complex synthetic circuit.
The new techniques could be used not only to sense environmental changes, but to work out the optimal environment for a cell to survive.
“If a cell needs to find the right microenvironment — glucose, pH, temperature and osmolarity [solute concentration] — individually they’re not very specific, but getting all four of those things really narrows it down,” Voigt says.
Currently, the scientists are working on a sensor that will allow yeast to monitor their own environment and adjust protein output accordingly to compensate. The research was funded by the U.S. Office of Naval Research and the National Institutes of Health.
Image credit: NIH / MIT