The lab of Kai Johnsson at EPFL, led by Alberto Schena and Rudolf Griss, were able to add a small chemical tag on the enzyme luciferase, which produces the light of fireflies. The tag detects a target protein, and the luciferase gives out a light signal that can be seen with a naked eye.
The team has proven expertise in this field: in 2014, they developed a quick and easy drug-monitoring molecule that led to a startup company, Lucentix. Thinking outside the box, they bypassed the pains of protein engineering altogether: instead of mutating the luciferase to make it sensitive for a target protein — which would require enormous labor — they simply attached it to a small chemical tag.
The tag acts as a switch: it blocks luciferase, preventing it from producing light. When the tag detects its target protein, it attaches to that instead, removing the block from lucifarase. As a result, luciferase is free to turn on the lights, which is the signal that the target has been found. In short, the scientists have created a chemical solution for a biological problem.
“You can think of the tagged luciferase as a cyborg molecule,” says Kai Johnsson. “Half bio, half synthetic. How could you make luciferase sensitive to the presence of another protein just through mutations? It’s a lot of work. With this chemical trick, all we have to worry about is designing an appropriate tag that can recognize the target protein.”
The activation of luciferase when it detects its target protein is dramatic enough to see with a naked eye. This means that the system does not demand expensive and complicated readout devices.
But the success has wider implications. “This is a generalized design,” says Kai Johnsson. “It shows how you can exploit synthetic chemistry to create sophisticated biosensor proteins.”
The study done by Ecole Polytechnique Fédérale de Lausanne.