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Biological Chemistry

Biologists Engineer A Three-Gene Optogenetic System

Synthetic Biology: New blue-light-active protein offers researchers ability to turn on genes with red, blue, and ultraviolet-B light

by Jyoti Madhusoodanan
November 12, 2014

With optogenetics, researchers can turn genes on and off by hitting cells with light. Now researchers have a new tool for the technique. A fresh mix of light-sensitive proteins can simultaneously target three genes within the same mammalian cell using three wavelengths of light, enabling more precise control of gene and protein networks (ACS Synth. Biol. 2014, DOI: 10.1021/sb500305v).

“Previously, we had systems to control one or two processes at a time,” says Matias D. Zurbriggen of the University of Freiburg, in Germany. Scientists typically rely on photoreceptor proteins that absorb light in the red, blue, or ultraviolet-B wavelength range. When activated by light, these molecules change shape or become unstable; the switch in their structure triggers activity of the genes they control. But current blue and UV-B photoreceptors absorb overlapping wavelength ranges and once active, take hours to subside—making them impossible to use together.

Using a mathematical model, Zurbriggen and his colleagues discovered that a three-color system needed a blue photoreceptor that inactivated within seconds, not hours. A literature search revealed an engineered protein derived from one in the oat plant (Avena sativa) that functions in precisely this way. This fast-acting photoreceptor contains an α-helix that, in the dark, binds to the rest of the protein to form a cage around the target gene’s promoter to block the cell’s transcriptional machinery. When hit with blue light, the helix releases, activating the target gene.

Using this protein with two other photoreceptors, the team could control the activity of three genes inserted into cultured mammalian cells using wavelengths of 311-nm UV-B, 450-nm blue, and 660-nm red light. With wavelength ranges that didn’t overlap and a quickly extinguished blue-light receptor, the researchers could control each gene independently.


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