From One to Many: How a GPCR Curiosity Became a Field-Wide Toolkit
- Dr. GPCR Podcast
- May 29
- 2 min read
What started with a single receptor became a toolset for an entire superfamily.
Dr. Tom Sakmar didn’t set out to map GPCR-RAMP interactions across hundreds of receptors. In fact, it all began with a phone call (from Bruce Merrifield, no less) encouraging Sakmar to work on the glucagon receptor. That early curiosity around Family B GPCRs set a 30-year trajectory in motion, culminating in a scalable, multiplexed platform to investigate GPCR-RAMP biology like never before.
A Long-Term Obsession, Reframed
Sakmar’s lab had been focused on the secretin receptor family for decades. But a question kept returning: How do RAMPs expand signaling diversity? The key realization was that these small, single-transmembrane proteins weren’t just chaperones; they actively shaped receptor pharmacology.
It was graduate student Emily Lorenzen who helped frame the next step: stop studying one receptor at a time. With the help of Luminex technology and collaborators at SciLifeLab in Sweden, the lab built a multiplex assay to study dozens of interactions simultaneously.
“The beauty of multiplexing is that you can do many things with one pot of samples.” — Tom Sakmar
Enter the Toolkit
As the pilot data came together, rotation student Ilana Kotliar joined and pushed the project to scale across all GPCR classes. What emerged was a dual-tagged GPCR library (DUET constructs), now publicly available via Addgene, and an online platform to query GPCR-RAMP interaction data and antibody validations.
These tools are already in use by labs around the world, with over 500 clone requests processed.
Why It Matters
This isn’t just a dataset, it’s a shift in how GPCR biology is approached:
Study known & orphan GPCRs
Identify new accessory protein interactions
Build disease-relevant signaling models
Validate antibodies for hard-to-study receptors
And most importantly, it’s free to academics, built for the community.
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