Dr. GPCR Podcast

Dr. Yamina Berchiche

We bring you closer to dedicated scientists who work tirelessly to help understand GPCR pathophysiology.

  1. 4d ago

    He Left Stanford to Decode Adhesion GPCRs - Antony Boucard

    Adhesion GPCRs are the largest receptors in the human genome — and until recently, no one was certain they coupled to G proteins at all. Boucard is working to change that, one synapse at a time. Antony Boucard didn't plan to be a scientist. He was heading toward medical school — fresh from social work in Nicaragua, where he built wood-burning ovens for women's cooperatives, and years of service in the Canadian Navy Reserve — when a summer in a biochemistry lab changed his trajectory entirely. He turned down his medical school acceptance and never looked back. After graduate training at the Université de Sherbrooke, a postdoctoral fellowship in Thomas Südhof's Nobel Prize-winning lab (first at UT Southwestern in Dallas, then at Stanford) opened a new research direction: the molecular code governing synapse formation. A chance experiment — testing whether a cell adhesion molecule he was studying might bind to a GPCR — yielded a result that Südhof himself didn't believe at first. Both proteins, it turned out, were independently known to bind alpha-latrotoxin, the toxin from black widow spider venom. No one had thought to ask whether they interacted with each other. That question has defined Boucard's lab ever since. Now at UNAM in Mexico City — where no lab was working on adhesion GPCRs when he arrived — he is building a research program that connects these colossal, largely orphan receptors to synapse specificity, addiction, autism, schizophrenia, bipolar disorder, and cancer. The conversation covers the science, the serendipitous path behind it, and what it looks like to pioneer a research field in a place no one expected. Why adhesion GPCRs are structurally unlike any other GPCR family — sprawling N-terminal domains, autoproteolytic processing, up to 1,000 amino acids — and what made them so difficult to work with for so longHow alpha-latrotoxin from black widow spider venom became the unexpected clue connecting a cell adhesion molecule and a GPCR into the same intercellular complexWhat synapse formation reveals about adhesion GPCR function — and how addiction, autism, schizophrenia, and cancer all converge on the same receptor biologyWhy Boucard left Stanford and UT Southwestern to build a lab at UNAM, and what it means to recruit from scientific communities that larger institutions overlookThe assays the lab uses to probe adhesion GPCR biology: BRET, FRET, microscopy, flow cytometry, and custom protein engineering strategies to solubilize membrane-anchored ligandsThe dream tool he can't build yet — a nanoscale real-time camera navigating the cell surface — and why cryo-EM snapshots still miss the most important part Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/ Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricingWeekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    He Left Stanford to Decode Adhesion GPCRs - Antony Boucard
  2. Aug 12

    The GPCR Nobody Has Learned to Drug Yet — Schulte

    Frizzled receptors look like GPCRs — but the field is split on whether they actually are. Gunnar Schulte has spent 25 years building the case, one receptor at a time. Schulte is a professor at Karolinska Institute in Stockholm, where his lab investigates Wnt–frizzled signaling at the molecular level. His research maps G-protein coupling specificity across all 10 frizzled subtypes, develops conformational biosensors to detect receptor activation, and searches for small molecules that could finally make frizzled receptors pharmacologically tractable. In this conversation, he walks through the evidence — what the conformational data show, why the Wnt ligand problem has stalled the field for decades, and how a compound originally designed for Smoothened became the closest thing frizzled pharmacology has to a starting point. Why each frizzled subtype couples to a different G protein — and why that distinction changes how the field should think about targeting themWhy 19 Wnt ligands remain almost impossible to work with, and what the lipid modification problem costs drug discoveryHow SAG1.3, a Smoothened agonist, became the first small molecule to activate frizzled 6 as a partial agonistWhat conformational sensors reveal about frizzled activation — and why Schulte considers this his strongest argument for their GPCR identityHow disheveled and G proteins may compete for receptor access through conformational selection Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/ Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricingWeekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    The GPCR Nobody Has Learned to Drug Yet — Schulte
  3. Jul 22

    The Off-Rate Nobody Measured

    Same binding affinity. Same target. One compound worked in vivo. The other did nothing. The answer was how long each molecule stayed on the CRF receptor — seven hours versus fifteen minutes — and no one had thought to measure it. Sam Hoare spent 15 years at Neurocrin Biosciences before founding PharmaChanics, a pharmacology data analysis consultancy built on one conviction: most GPCR teams are collecting data they don't know how to analyze. In this conversation, Hoare walks through the off-rate discovery that redirected an entire drug program, the signaling kinetics framework he developed to fill a gap no one had formally acknowledged, and what it actually takes to move from industry scientist to independent consultant. Along the way: why GPCRs are the most tractable system in pharmacology — and why that still isn't enough if the analysis is wrong. How receptor residence time — not affinity — determined which CRF compound reached Phase 2Why time-course signaling data is routinely collected but almost never analyzed with the rigor applied to dose-response curvesWhat 15 years of GPCR drug discovery taught Hoare about the gap between understanding a receptor and making a drug for itHow early-career researchers can leverage deep target expertise to build a consulting practiceThe three aha moments that have kept a pharmacological data analyst motivated across a 30-year career Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricingWeekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    The Off-Rate Nobody Measured
  4. Jul 8

    The Accident That Built the GPCR Field — Bob Lefkowitz

    Lefkowitz was told in 1973 that hormone receptors were a figment of his imagination. The work that proved otherwise became the molecular foundation of GPCR pharmacology. Nobel laureate Robert Lefkowitz traces the full arc of GPCR discovery — from developing the first radioligand for the beta-adrenergic receptor to purifying it, cloning it, and watching a sequencing run reveal structural homology with rhodopsin that nobody in the field had predicted. That 1986 paper established the GPCR superfamily. The same system yielded the GRK family and the beta-arrestins. This conversation is also about the human architecture behind that science: how a Vietnam War draft assignment in 1968 redirected a physician toward a question the field wasn't sure was real, what 18 months of unbroken failure at the NIH taught him about research, and why he argues that if 50% of your experiments succeed, you are not working on hard enough problems. How a Vietnam War draft sent a physician to the NIH — and gave rise to 50 years of GPCR receptor pharmacologyWhy Lefkowitz chose the beta-adrenergic system, and why he considers it the smartest scientific decision of his careerThe cloning race against Genentech: the "stupid idea" that worked and the intronless gene that ended the competitionHigh output vs. low output failure — how to find the research territory between trivial problems and intractable onesWhat the Nobel call at 5 AM actually felt like: not jubilation, but relief — and a tear when he learned who he'd share it with Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/ Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricingWeekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    The Accident That Built the GPCR Field — Bob Lefkowitz
  5. Jun 17

    The GPCR Antibody Nobody Could Validate - GeneTex - Alexander Ball & Chia-Yi Lin

    Most GPCR antibody failures are silent. The signal looks clean, the band is there, the experiment moves forward - until someone runs a knockout control and the signal is still there. Lin and Ball have spent years building reagents for exactly this problem, and this conversation gets into the details of what reliable GPCR antibody characterization actually requires. Chia-Yi Lin and Alexander Ball are scientists-turned-industry professionals at GeneTex, a company that has shifted its entire new antibody production to recombinant monoclonal technology since 2019. In this conversation, they trace the arc from GeneTex's founding by cancer biology researchers in 1990s Texas to its current position as a growing source of characterized GPCR research reagents. The discussion covers why GPCR targets are especially difficult immunogen design problems, what five-pillar antibody characterization looks like for receptors like LGR5 and the chemokine receptor family, and why the word "characterized" may be more scientifically honest than "validated" when describing what an antibody data sheet actually tells you. Ball's path from medicine to the bench to industry - and Lin's from stem cell biology to leading international operations at GeneTex - brings a rare dual perspective to a problem that most researchers only see from one side. Key topics covered: Why GPCR family homology - including the 75% sequence identity between CXCR1 and CXCR2 - makes immunogen selection the critical upstream decision in antibody development, often determining success or failure before a single experiment is run What five-pillar characterization looks like in practice: KO and KD validation, comparable antibody testing, cell fractionation, tissue orthogonal testing, and GPCR virion arrays from CDI Labs How recombinant monoclonal antibodies solve the batch variability problem that polyclonal production cannot - and why a sequence defined in a plasmid changes reproducibility for the entire field The LGR5 story: how one leucine-rich repeat GPCR critical to intestinal stem cell biology became GeneTex's defining early challenge - and why Ball's company president went pale when the target came up Why Ball and Lin encourage researchers to contact the company directly before purchasing, what questions to ask, and how a free GPCR antibody sample program is actively connecting the community with reagents that need real-system testing Dr. GPCR Links and Resources Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/Membership and Pricing: https://www.ecosystem.drgpcr.com/university-pricingWeekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    The GPCR Antibody Nobody Could Validate - GeneTex - Alexander Ball & Chia-Yi Lin
  6. May 27

    Three Adhesion GPCRs and No Rulebook - Beatriz Blanco

    Most receptors come with a history. Remulate came with a name — and almost nothing else. Dr. Beatriz Redondo, group leader at the University of Leipzig, has spent the last nine years building the first systematic characterization of adhesion GPCRs in Drosophila, including three receptors so new they were named after condiments. What she's constructing isn't just a receptor profile — it's a method for doing discovery when the tools don't exist yet. Dr. Redondo uses CRISPR, genetic tagging, and in vivo behavioral assays to place and characterize adhesion GPCRs in a system where generations turn over in weeks. Her work on remulate — a neuronal adhesion GPCR with a human ortholog linked to vascular malformations and blood-brain barrier dysfunction — is among the first of its kind in any organism. Key takeaways: Why Drosophila remains a productive system for receptor discovery in the genomics eraHow CRISPR and epitope tagging replace antibody-based tools for understudied GPCRsWhat nocifensive behavior in larvae reveals about remulate's neuronal functionHow basic science in an insect model connects to vertebrate disease biologyWhat it looks like to characterize a receptor from scratch — with no prior literature to build on Dr. GPCR University — live and on-demand courses for scientists working on real discovery problems: https://www.ecosystem.drgpcr.com/gpcr-university This episode is supported by Eurofins DiscoverX and GeneTex: https://www.ecosystem.drgpcr.com/eurofins-discoverx | https://www.ecosystem.drgpcr.com/genetex

    Three Adhesion GPCRs and No Rulebook - Beatriz Blanco
  7. May 13

    Chimeric GPCRs: Why the Easy Designs Fail — Charlotte Crauwels

    What if two nearly identical GPCRs make a worse chimera than two receptors from completely different classes? Charlotte Crauwels is building computational tools to find out why — and to predict which designs will work before they reach the bench. Crauwels develops in silico pipelines for chimeric GPCR design at the Free University of Brussels. Her work sits at the interface of computational prediction and experimental validation, addressing a problem the field has struggled with for decades: chimeric constructs are powerful but unpredictable, and the data surrounding them is scattered, inconsistently named, and poorly annotated. After spending over a year collecting and standardizing published chimeric GPCR data, she built GPCR ChimeraDB — one of the first public databases dedicated to these constructs. Key takeaways: How chimeric GPCRs can deorphanize receptors and reveal signaling pathways that were previously inaccessibleWhy computational ranking of chimeric candidates replaces trial-and-error in the labWhat inconsistent nomenclature and missing annotations cost the field — and how better data sharing changes the gameWhy the feedback loop between computational and experimental scientists is non-negotiable for GPCR research Dr. GPCR Links & Resources Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricingWeekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    Chimeric GPCRs: Why the Easy Designs Fail — Charlotte Crauwels

Ratings & Reviews

4.8
out of 5
12 Ratings

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We bring you closer to dedicated scientists who work tirelessly to help understand GPCR pathophysiology.

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