G protein-coupled receptor
102
MENTIONS
10
EPISODES
9
PODCASTS
Search complete. 102 mentions across 10 episodes found for "G protein-coupled receptor".
Sep 9, 2026
Emmanuel MignotGUEST
That is true.
Emmanuel MignotGUEST
So wh- when we found the gene and, uh, I mean, uh, you know, the first thing that people were super excited is, "Oh my God, it's called a GPCR," which of course is where Masashi started.
Emmanuel MignotGUEST
You know, it's a drug target.
Emmanuel MignotGUEST
You know? This is like the best receptor.
9 MINS LATER
Masashi YanagisawaGUEST
And yet, still, uh, some patients are suffering from, uh, so-called, you know, hyperarousal state, which orexin blockers can correct to some extent.
Masashi YanagisawaGUEST
So that's how orexin receptor antagonists work.
Masashi YanagisawaGUEST
And, you know, when it comes to those drugs, certainly making this peptide GPCR antagonist is technically much less challenging as compared with making agonist.
Masashi YanagisawaGUEST
That's why one of the major reasons why it took so long to make a agonist after antagonist.
YaminaHOST
This episode is supported by two companies invested in advancing GPCR research, Gentex and Eurofins DiscoverX.
YaminaHOST
Eurofins DiscoverX provides the assay infrastructure serious GPCR programs depend on, validated, scalable, and built for decisions that matter from early discovery through regulatory review.
YaminaHOST
And Gentex is raising the bar on GPCR antibody reliability through rigorous validation and open community engagement with you.
YaminaHOST
Their catalog is growing and your free sample request is welcome.
YaminaHOST
Links to both in the show notes.
YaminaHOST
And now let's dive into this episode.
YaminaHOST
Hello, everyone.
YaminaHOST
This is Yamina from Dr. GPCR, and today we're recording a special Dr. GPCR podcast episode.
Luca TurinGUEST
So when the evidence for the, the vibrational theory was published, a lot of people who worked, let me qualify this, a lot of people who thought they knew a lot about G-protein coupled receptors were very angry because they rightly said, since the olfactory receptors are G-protein coupled, if you say that those receptors are electrically powered, that's it.
Luca TurinGUEST
then that's weird because why would nature, why would evolution endow only one class of G protein couple receptors with this electrical wiring and leave the other ones untouched? And I think that's a terrific objection, so much so that I've been thinking a lot recently about the fact that I believe all GPCRs are electrical devices.
Luca TurinGUEST
And therefore, interestingly, there's no point in working on olfactory receptors to prove this, because any GPCR will do, and many are more amenable to study than olfactory receptors.
Luca TurinGUEST
But let me explain why this may actually be correct.
EvanHOST
Yes.
Luca TurinGUEST
Now, that is the fundamental transduction problem of a receptor, which I consider to be the most interesting part.
Luca TurinGUEST
And I believe that the people at the core phase of GPCRs are fully aware of this.
Luca TurinGUEST
But they're wedded to, in my opinion, a completely wrong notion that all of GPCR activation occurs at thermal equilibrium.
Stephanie WankowiczHOST
And so, and that's a huge part of grant writing.
James FraserHOST
And to return to the recurring theme from the Claude and example right before, right? It's not like the prompt for these is write an R01 on opioid addiction and GPCR signaling.
James FraserHOST
It's, it's probably, you know, a huge prompt, a huge amount of notes and prior literature outlines and stuff like that, that are, you know, being crafted and, and the LLM is being used to write certain sections or refine certain sections, edit it rather than just write a grant de novo.
James FraserHOST
Although I'm, I'm sure there are also people who are basically saying, like, here's my last paper, write an R01 on what's next.
Sam SmithHOST
So the inflammatory pathway that's activated can be a ton, a ton, a ton of different types of pathways.
Sam SmithHOST
These can be GPCR pathways, G-coupled protein receptors, and it's gonna be toll-like receptors.
Sam SmithHOST
When I was looking through, like, a page of all the different inflammatory pathways in cells, there's just, like, a million of them.
Sam SmithHOST
So, you know, I don't think you really have to know specific pathways for the MCAT.
Peter KolchinskyGUEST
Uh, and so, uh, I s- you know, researched like, you know, what I needed to know about his technology to formulate something of a business plan.
Peter KolchinskyGUEST
His basic idea was that he'd found a way to reconstitute a, uh, lipid bilayer with a purified membrane, um, you know, protein, uh, so that you could have a bead with like a GPCR in its native conformation on the surface of the bead, like just that one pure GPCR on it, which you could imagine if you injected such a bead into, um, you know, a, a mouse, you'd be able to, uh, you know, derive antibodies against that one GPCR.
Peter KolchinskyGUEST
Up until that point, people were injecting like whole cells or partial, you know, sort of GPCRs embedded in, uh, sort of fragments of layers, uh, lipid bilayer.
Sean KhozinHOST
Right.
Peter KolchinskyGUEST
And so, um-
Martha PetrocheilosHOST
What led you to concentrate there?
Sri KosuriGUEST
This goes back to the lessons of what we were naive about and what we weren't, right? We had started with this idea in dirty drugs in, uh, a class of receptors called GPCRs, where there's a lot of polypharmacology where a small molecule can hit many things, and that's essential for their function, and bias, which is multiple pathways off the same target.
Sri KosuriGUEST
We switched largely because we began to realize that if we wanted to build scale and our own commercial drugs, it's really hard to do that in a large, complex disease area.
Sri KosuriGUEST
Your only option really is to transact the asset where value and flex.
Jens HeitlandHOST
But if we look at the bigger picture, where do you think that that can lead
Kambiz ShekdarGUEST
to? I think if we had the full resources to crank out all these cells that, you know, there are entire biotechs working on one GPCR.
Kambiz ShekdarGUEST
If we can crank out all 400 and get interesting compounds to all of them and then form collaborations where we feed these compounds into companies that exist, that are working to develop drugs in their therapeutic areas.
Kambiz ShekdarGUEST
we could maybe unleash a torrent of, you know, much more effective drug discovery.
Martin PicardGUEST
Like, the textbook doesn't...
Martin PicardGUEST
The textbook I studied never talked about GPCRs in the mitochondrial membrane.
Martin PicardGUEST
Um, so that was really surprising.
Martin PicardGUEST
I mean, I think the first paper was in na- in Nature or Nature Neuroscience, uh, CB1 and mitochondria from a group in Bordeaux.
Tracy MullenHOST
It was really because we kept seeing that programs coming through our door required additional, more sophisticated approaches.
Tracy MullenHOST
More and more clients were bringing us harder targets, complex cell surface receptors, GPCRs, ion channels, other multi-pass transmembrane proteins, And for these types of targets, it can be challenging, although not impossible, but challenging to leverage alternative platforms like in vitro display for antibody discovery purposes.
Tracy MullenHOST
The other thing that we were noticing was how often time and costs were lost in the handoffs, starting with native wild type animals.
Tracy MullenHOST
So when you start from a fully human transgenic model, you get to skip that humanization step entirely downstream.
Dan RohrerGUEST
But in addition to those aspects, we also are bringing on new model types altogether that are really addressing more modern therapeutic needs.
Dan RohrerGUEST
And to that end, we're talking about a bispecific binary fixed light chain model, which assists in making either bi- or multi-specific antibodies.
Dan RohrerGUEST
as well as our long CDR3 model, which is actually leveraging longer CDR3s to get at difficult targets like GPCRs and ion channels.
Dan RohrerGUEST
So, you know, taken as a whole, improving on the full diversity standard offering, as well as the other two models, we really believe we're kind of in this third gen space and can help address almost any kind of target type that might come to you guys.