Dr. GPCR Podcast

Dr. Yamina Berchiche

0.0 (0)
Life Sciences
Updated Biweekly

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

6d ago

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
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
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
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
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
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
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
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

Trailer

Episode #0 Dr. GPCR Podcast

In this Episode 0 of the podcast, I, Dr. Yamina Bechiche, your host, and founder of DrGPCR introduce you to the very first podcast dedicated to GPCR researchers and their work. This podcast is part of the Dr. GPCR Ecosystem. The goal is to bring us together GPCR scientists, biotech, and pharma leaders as well as suppliers working on GPCRs. We want to provide opportunities to connect, share, form trusting partnerships, grow, and thrive together to accelerate GPCR drug discovery and improve human health. For more information visit us at DrGPCR.com/Podcast and join the DrGPCR Ecosystem at DrGPCR.com/Ecosystem. Don't forget to subscribe to our monthly newsletter at DrGPCR.com/Newsletter.

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

Creator

Dr. Yamina Berchiche
Years Active

2021 - 2026
Episodes

228
Rating

Explicit
Copyright

© Dr. Yamina Berchiche
Show Website

Dr. GPCR Podcast