Firefly enzyme used for protein detection

The detection of biological molecules is vital in many fields; however, current detection methods are often time consuming, labor intensive and expensive. École Polytechnique Fédérale de Lausanne (EPFL; Switzerland) scientists have tweaked the enzyme responsible for the light of fireflies, luciferase, so that it is capable of releasing light in the presence of target molecules. The system is cheap, simple and highly accurate. Their work was published recently in Nature Communications.

Study leaders Alberto Schena and Rudolf Griss (both Postdoctoral Researchers at EPFL) added a small chemical tag to the enzyme luciferase. When the tag detects the protein, the luciferase produces a light signal. This approach meant protein engineering was avoided – this would have involved mutating the luciferase to make it sensitive for a target protein, requiring enormous amounts of labor.

The tag acts as a switch, preventing luciferase from releasing light by binding it when no target protein is present. When the tag detects a target protein, it binds the protein instead of the luciferase, allowing luciferase to release light. The light therefore signifies that the target has been found.

“You can think of the tagged luciferase as a cyborg molecule,” said Kai Johnsson (Professor at EPFL and corresponding author). “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 in the presence of target protein is strong enough to be seen with the naked eye. This means that expensive and complicated readout devices are not required.

Looking to the future, Kai Johnsson believes the device has wider applications. He commented, “This is a generalized design. It shows how you can exploit synthetic chemistry to create sophisticated biosensor proteins.”

Sources: Schena A, Griss R, Johnsson K. Modulating protein activity using tethered ligands with mutually exclusive binding sites. Nat. Comms. DOI: 10.1038/ncomms8830 (2015); The light of fireflies for medical diagnostics.