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Stanford University School of Medicine

New technology reveals surprise immune system discovery

3123229023_e50c456e91_zThis story would be a simple tale of helpful new technology - of which I've written a lot - but it also goes to show how new technology can reveal fundamentally new biology. In this case: a surprise discovery that could be important for understanding immune disease and treating cancer by immunotherapy.

A key part of biology - from understanding basic processes to developing drugs - is knowing which proteins interact. Right now, the best way of sussing out those interactions requires a lot of biological reagents. It can also  only investigate one set of proteins at a time, and it isn't very good at detecting weak interactions that might still be really important in biology.

This is more than just an academic bummer. Without a good way of detecting protein interactions it's difficult to tease apart how our bodies work at the most fundamental level. Also, it can slow the development of drugs that tap into those interactions.

Postdoctoral fellow Jung-Rok Lee, PhD, worked with Stanford engineering professor Shan Wang, PhD, to improve those odds. He attached the proteins of interest to tiny magnetic nanoparticles. They then squirted those proteins through little channels that went across a surface coated in a protein.

If the protein flowing through the channel interacts with the surface, a magnetic sensor detects the nanoparticles glomming up rather than marching steadily along the channel. That sensor would also notice if the proteins bound weakly because it would detect nanoparticles stopping and starting along the journey down the channel.

"The nice thing about the nanosensor is that it's a real time measurement," Lee told me. They reported their technique last week in Nature Communications.

Also, just to list off the benefits, this device can have many different channels containing many different proteins all running across the surface at once.

Chemist Chaitan Khosla, PhD, who directs the institute Stanford ChEM-H, told me that the technique is a big advance: "The ability to precisely measure the affinity between weakly interacting proteins is a big problem in chemistry with enormous implications in biomedicine."

But here's where the surprise discovery comes in. Lee and Wang tested their technique using a few proteins that are known to interact (and a few that aren't) in the process of regulating the immune checkpoint that is important to human health and new cancer therapy. These are well known proteins and seemed like a safe way of seeing if their idea worked as expected.

It turns out their system is so sensitive it detected a completely novel interaction. The two were so surprised they didn't report their discovery until collaborators at Genentech confirmed it on their own equipment.

Wang is now hoping to follow up on the surprise discovery with Khosla and ChEM-H, which focuses on chemistry and engineering for human health. They think it's possible that the novel protein interaction could point to a possible way of regulating and even treating diseases of the immune system, or for developing immunotherapy approaches for treating cancer.

Previously: Fighting cancer on a tiny stage and Stanford-developed smart phone blood-testing device wins international award
Photo by Tom Woodward

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