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New light-based systems turns off protein production

A novel light-controlled ‘off’ switch for proteins will open up new ways to explore how many important cellular processes work.

A collaboration between the UK Centre for Mammalian Synthetic Biology (Jamie Davies and Elise Cachat) and groups based in Germany, have harnessed optogenetics – light controlled switches of gene expression – to switch off protein production.

Most researchers study what a protein does in a cell by artificially manipulating its production. Many use chemicals to control the process but these can be toxic and have unexpected side effects.

Optogenetics offers a solution. Researchers build light-sensitive detectors into the molecular controllers of protein production and then trigger these with a beam of light. The technique can target cells with higher accuracy then chemicals and works in both cell cultures and in living animals. However, it has proven very difficult to create optogenetic systems that turn off protein production.

To address this, the team built a two-component, blue light-responsive optogenetic OFF switch (‘Blue-OFF’), which quickly reduces how much protein is made when illuminated. They combined a light responsive unit (KRAB-EL222), which halts protein production on illumination, with a module (B-LID) that marks proteins for degradation. So blue light targeted both gene expression and protein stability creating a fast and powerful response.

The researchers then showed that they could use the system to control cell death in a culture of human cells. This exciting new approach opens up novel perspectives in fundamental research and applications such as tissue engineering.

 

Dual-controlled optogenetic system for the rapid down-regulation of protein levels in mammalian cells Baaske, J et al. Scientific Reports Volume 8, Article number: 15024 (2018)