Dr. GPCR Podcast

Dr. Yamina Berchiche
  • 4.8 (12)
  • Life Sciences
  • Updated Monthly

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

  1. The Accident That Built the GPCR Field — Bob Lefkowitz

    3h ago

    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

    1h 31m
  2. The GPCR Antibody Nobody Could Validate - GeneTex - Alexander Ball & Chia-Yi Lin

    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

    41 min
  3. Three Adhesion GPCRs and No Rulebook - Beatriz Blanco

    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

    44 min
  4. Chimeric GPCRs: Why the Easy Designs Fail — Charlotte Crauwels

    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

    48 min
  5. The Beta-2 Agonist That Doesn't Stop Working — Tore Bengtsson

    May 6

    The Beta-2 Agonist That Doesn't Stop Working — Tore Bengtsson

    Every beta-2 agonist ever tested for muscle growth hits the same wall: desensitization. Dr. Tore Bengtsson built one that doesn't. A professor at Stockholm University and founder of Atrogi, Dr. Bengtsson has spent 25 years studying how beta-adrenergic receptors regulate metabolism, muscle, and brown fat. His lab developed 1,500+ compounds that activate beta-2 through distinct signaling pathways, and one is now heading into Phase 2 clinical trials. He shares how a "failed" experiment cracked the problem, why incretins only address half of metabolic disease problems, and what muscle loss after 50 means for drug discovery strategy. Key takeaways: Classical beta-2 agonists fail because desensitization shuts down the responseSelectively activating specific signaling pathways from one receptor can produce entirely different outcomesIncretins reduce energy intake — but the energy expenditure side remains wide openThe correlation between muscle mass and longevity is one of the most underserved areas in metabolic medicine🔗 Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/ 🎓 Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricing 📰 Weekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    46 min
  6. One Molecule, Two Opioid Receptors - Joseph Kim

    Apr 29

    One Molecule, Two Opioid Receptors - Joseph Kim

    Dr. Joseph Kim solved cryo-EM structures of mu and kappa opioid receptors bound to the same small molecule — and found it does something different at each one. In this conversation, Dr. Kim walks through his transition from cryo-electron tomography to GPCR structural biology in Ashish Manglik's lab at UCSF, the strategy behind solving inactive-state receptor structures, and why his favorite GPCR — the galanin receptor — has resisted every small-molecule screen thrown at it. Key takeaways: How one molecule acts as an antagonist at mu and an inverse agonist at kappaWhy the galanin receptor's peptide binding mode blocks conventional drug discoveryWhat it takes to switch fields with no prior biochemistry trainingHow building tools on "vanilla" GPCRs prepares you for exotic targets 🔬 Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/ 💰 Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricing 📰 Weekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    50 min
  7. Can Simulations Predict GPCR Ligand Bias?

    Mar 18

    Can Simulations Predict GPCR Ligand Bias?

    How does ligand binding at the extracellular pocket of a GPCR reshape signaling on the intracellular side? Biased agonism is often measured through pathway activation assays, but the structural origin of ligand bias remains difficult to trace. Can molecular simulations reveal the communication routes that link ligand binding to G protein or arrestin signaling? In this conversation, computational biologist Anita Niveda explores how molecular dynamics and network analysis can map allosteric communication within GPCRs—revealing how microscopic structural pathways relate to macroscopic signaling outcomes. From discovering bioinformatics as an undergraduate to developing computational methods for quantifying ligand bias, the discussion moves through the scientific thinking behind modeling receptor signaling, collaborations between academia and industry, and how computational tools are becoming predictive instruments in drug discovery. Key Topics in This Episode How molecular dynamics simulations reveal communication pathways connecting ligand binding sites to G protein or arrestin interfaces Why mapping allosteric communication networks helps explain biased agonism in GPCR signaling What computational strategies can quantify ligand bias directly from receptor structures How receptor subtype selectivity emerges from subtle structural and dynamic differences in binding pockets Why academic–industry collaborations can accelerate method development in receptor pharmacology What career decisions shape the path from computational biology training to drug discovery roles Timestamps 0:00 A structural question behind ligand bias1:30 Introduction and scientific background3:40 Discovering bioinformatics and computational biology7:30 First encounters with GPCR structural biology9:40 Finding and choosing a postdoctoral lab16:40 Entering GPCR research and allosteric communication18:20 Quantifying ligand bias using simulations20:00 Mapping signaling pathways through receptor residues23:30 Academic–industry collaboration with Boehringer Ingelheim27:00 Moving from academia to industry research35:00 Interviewing and transitioning into biotech45:00 Aha moments in computational GPCR research50:00 The diversity of GPCR families and signaling biology Keywords: GPCR podcast, GPCR signaling, biased agonism, drug discovery, receptor pharmacology

    55 min
  8. Why Mosquitoes Hunt You: The GPCR Behind the Bite - Laura Duvall

    Mar 4

    Why Mosquitoes Hunt You: The GPCR Behind the Bite - Laura Duvall

    Conserved neuropeptide Y GPCRs orchestrate both feeding and mating behaviors in mosquitoes, with direct translational parallels to human gut-brain signaling. Quick Summary Learn how receptor internalization and neuropeptide GPCR signaling underlie the regulation of mosquito host-seeking and reproduction. Dr. Laura Duvall details the use of CRISPR-based assay development and fluorescence-driven phenotyping to connect molecular manipulation to whole-animal behavior. Her approach provides actionable insights for gpcr drug discovery and tools to dissect homologous pathways across model systems, with implications for pharmacology research targeting vector-borne disease transmission. Key Takeaways Neuropeptide Y GPCRs modulate both host attraction and mating in Aedes aegypti. CRISPR and fluorescence assays enable precise behavioral phenotyping in vivo. GPCR-targeted compounds designed for humans can modulate mosquito receptors. NPY receptor expression in mosquito gut mirrors mammalian gut-brain signaling axes. Automated behavioral assays combined with machine learning sharpen data resolution and reduce human bias. Dr. GPCR Links & Resources Explore essential resources: Dr. GPCR Ecosystem Membership & Pricing Weekly News Advance your research—discover the power of Dr. GPCR Premium. About the Guest Dr. Laura Duvall earned her B.A. in Biochemistry and Biological Basis of Behavior from the University of Pennsylvania, followed by a PhD at Washington University in St. Louis, where she explored neuropeptide regulation of circadian behavior in Drosophila. Transitioning from fruit flies to mosquitoes, she pursued postdoctoral research at Rockefeller University with Leslie Vosshall, focusing on the molecular regulation of feeding and mating behaviors in Aedes aegypti. In 2019, she established her independent laboratory at Columbia University's Department of Biological Sciences and the Zuckerman Institute. Dr. Duvall’s work is recognized by awards including the Beckman Young Investigator Award, Klingenstein-Simons Fellowship in Neuroscience, and the Pew Scholars Program, reflecting her drive to unravel the complex signaling mechanisms that govern mosquito and broader animal behavior. Guest on The Web LinkedIn: https://www.linkedin.com/in/laura-duvall-28a03485/ Google Scholar: https://scholar.google.com/citations?user=Vk3KGSoAAAAJ&hl=en Lab: https://www.duvalllab.com/

    51 min
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Ratings & Reviews

4.8
out of 5
12 Ratings

About

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

Information

  • Creator
    Dr. Yamina Berchiche
  • Years Active
    2020 - 2026
  • Episodes
    227
  • Rating
    Explicit
  • Copyright
    © Dr. Yamina Berchiche
  • Show Website
    Dr. GPCR Podcast

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