Check out those figure making skills! She should do Illustrator tutorials.

There's lots more in the paper, but I just want to emphasize that an ideal switch:
- Should be easily adapted to respond to other kinases.
- Should easily "plug into" other target proteins.

Both are true! For example, here is a "phospho-nanobody" that binds actin only when ERK phosphorylates it :)

Here's where Qinhao rolled up his sleeves and got to work, testing dozens of variants and optimizing every component to build a better phospho-switch.

His final version basically looks as good as regular Gal4 when ERK is on, and has a 20x change in gene expression between ERK-on and off states!

So the idea:
- Take an opto-Gal4 transcription factor we previously made by inserting the AsLOV2 switch
- Swap out AsLOV2 for a FRET biosensor for our favorite kinase, ERK
- Check if ERK activity now controls Gal4-induced gene expression!

It worked, but honestly, not that well...

Qinhao had a stroke of insight: a classic kinase biosensor design (FRET biosensors) look just like an opto-switch! Both have N and C termini that are close together in one state and far apart in another. It is this change in N-to-C distance that "pulls" on the target protein to turn it on or off.

This problem looks a lot like one we face in optogenetics: Given a protein, can I make a light-switchable version of it?

One way to do that is to fuse an "opto-switch" domain to a target protein. Light changes the conformation of the opto-switch, which tugs on the protein to turn it on or off!

I'd like to share a little bit of happy lab news in these chaotic times: a new preprint, driven by the brilliant Qinhao Cao!
www.biorxiv.org/content/10.1...
We address a big challenge in synbio: If you give me a protein "X", how can I give you a version of X whose activity is controlled by a kinase?

How do we expect science to be done around here if all the mugs are broken?