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A conversation with Charlotte Crauwels exploring computational protein design, hybrid GPCR constructs, and how computational pipelines can accelerate GPCR signaling research and drug discovery. << Back to podcast list Strategic Partner(s) Charlotte Crauwels: Designing Hybrid GPCRs with Computational Protein Engineering Scientific Abstract G protein–coupled receptors (GPCRs) are among the most extensively studied protein families in pharmacology and drug discovery, yet many receptors remain poorly characterized or “orphan,” lacking known endogenous ligands. In this conversation, Charlotte Crauwels discusses her work developing computational strategies to support the design of hybrid or chimeric GPCRs. Charlotte Crauwels’ research focuses on building computational pipelines that guide the rational design of GPCR chimeras by combining structural elements from well-characterized receptors with poorly understood ones. These hybrid receptors enable researchers to probe receptor signaling, investigate G protein coupling preferences, and explore structural determinants of receptor activation. By evaluating large numbers of candidate constructs in silico , computational screening can help prioritize experimental designs before testing in the laboratory. The discussion also explores the broader relationship between experimental and computational research in GPCR biology. Ms. Crauwels emphasizes the critical role of well-annotated experimental data for training predictive models and highlights the importance of collaboration between bench scientists and computational researchers. Listeners gain insight into how computational protein design can accelerate receptor signaling research and contribute to new approaches for GPCR discovery and pharmacological characterization. About the Guest Charlotte Crauwels is a computational scientist specializing in protein design and GPCR biology. She conducted her PhD at the Vrije Universiteit Brussel in the research group of Dr. Wim Vranken, focusing on computational approaches for GPCR engineering. Her research centers on developing computational pipelines that guide the design of hybrid or chimeric GPCR constructs to study receptor signaling and structural determinants of receptor activation. Her work integrates bioinformatics, protein modeling, and experimental collaboration to support GPCR discovery and functional characterization. Scientific Themes of the Conversation Computational protein design for GPCR engineering Hybrid and chimeric GPCR constructs Experimental–computational feedback loops in receptor biology Data quality and annotation in computational pharmacology Deorphanization strategies for poorly characterized GPCRs Structural determinants of GPCR signaling pathways Key Insights from the Conversation Experimental Data Drives Computational Discovery Computational models are fundamentally dependent on high-quality experimental data. Charlotte Crauwels emphasizes that predictive models are only as reliable as the datasets used to train them, highlighting the importance of properly annotated experimental datasets in GPCR pharmacology. Computational Tools Help Guide Experimental Design Rather than replacing experiments, computational approaches provide guidance. In Ms. Crauwels’ work, computational pipelines rank potential GPCR chimera designs, helping experimental scientists prioritize which constructs to test first in the lab. Hybrid GPCRs Provide Insight into Orphan Receptors Chimeric GPCR constructs combine components from well-characterized receptors with poorly understood receptors. This strategy can reveal signaling pathways or structural features of orphan GPCRs that cannot easily be studied otherwise. Collaboration Between Bench and Computational Scientists Is Essential Computational researchers depend on experimental validation, while experimental scientists benefit from predictive models that help narrow down possible hypotheses. Successful GPCR research increasingly depends on close collaboration between these two domains. Communication Challenges Between Research Disciplines Computational and experimental scientists often use different terminology and assumptions. Dr. Crauwels describes how misunderstandings can arise from differences in language, experimental details, or sequence definitions—highlighting the need for clear communication in interdisciplinary projects. Data Transparency Enables Better Models Publishing negative results and detailed experimental metadata can significantly improve computational models. Even unsuccessful experiments can contain valuable information for machine learning or predictive modeling. GPCR Biology Continues to Produce “Gotcha Moments” Despite decades of research, GPCRs remain complex and surprising. Dr. Crauwels notes that researchers often experience unexpected results that challenge assumptions about receptor signaling and structural behavior. Episode Timeline 00:00 — Introduction Introduction of Dr. Crauwels and her PhD work in computational GPCR research. 02:20 — Scientific Path Into Computational Biology How bioengineering and bioinformatics led Dr. Crauwels toward computational protein design. 09:15 — The Role of Computational Science in GPCR Research The relationship between experimental data and computational modeling. 16:00 — Collaboration Between Experimental and Computational Scientists Why feedback loops between lab work and computational analysis are critical. 26:30 — Designing Hybrid GPCR Constructs The concept of chimeric GPCRs and how they can be used to study receptor signaling. 30:00 — Building a Computational Pipeline for Chimera Design Using in silico modeling to rank candidate receptor designs before laboratory testing. 36:30 — GPCR ChimeraDB and Data Challenges The challenge of collecting standardized data on chimeric GPCR experiments. 41:30 — “Gotcha Moments” in GPCR Research Why GPCRs continue to surprise even experienced researchers. 43:50 — Advice for Young Computational Scientists The importance of collaboration, conferences, and stepping outside research silos. 48:20 — Career Reflections and What Comes Next Thoughts on the transition after a PhD and continuing research in GPCR biology. Selected Quotes “Computational work allows you to look at data from a different perspective and identify patterns that would be difficult to see experimentally.” “Garbage in, garbage out—computational models depend entirely on the quality of experimental data.” “Hybrid GPCRs allow us to use what we already know about one receptor to understand another that is poorly characterized.” “Every time you think you understand GPCRs, they surprise you again.” Full Transcript (Formatted for readability — original transcript preserved) Yamina Berchiche: Hello everyone. This is Yamina from Dr. GPCR, and today I'm very excited to have with me Charlotte Crauwels. Charlotte is finishing up her PhD, and we’ve been trying to sit down and have this conversation for quite some time. Charlotte, welcome to the podcast. Charlotte Crauwels: Thank you for having me. Yamina Berchiche: Why don't we start by you introducing yourself and telling us about what you're working on right now? Charlotte Crauwels: So as you mentioned, I’m a final-year PhD student at the Vrije Universiteit Brussel in Belgium. I work in the group of Dr. Wim Vranken. I would define myself as a computational protein designer focusing on GPCRs. Looking back, my path to this work was not very linear. I wasn’t originally planning to do a PhD, and I wasn’t planning to work on GPCRs either. I studied bioengineering in Brussels, and during my master’s I was introduced to bioinformatics. I discovered that I really enjoyed working with data and computational tools. For my master’s thesis, I studied antibodies and nanobodies and how they bind to their antigens. That experience convinced me that research might be something I wanted to pursue. At that time, I wasn’t sure what career direction I wanted, so I started contacting computational research groups in Belgium. Eventually, I connected with my current supervisor and began developing GPCR-related research projects. And by coincidence, I ended up working on GPCRs—and I’m actually very happy that I did. Yamina Berchiche: Looking back at your PhD trajectory, what originally drew you to computational research? Charlotte Crauwels: I think it was the idea that we now have enormous amounts of biological data available. We have powerful computational tools that allow us to explore biological systems in ways that were not possible before. So my motivation was really the idea of engineering life—using data and computational methods to understand biological systems and potentially optimize them. Yamina Berchiche: Computational scientists are not always well represented in GPCR discussions. How do you see the role of computational approaches in GPCR biology? Charlotte Crauwels: I think computational scientists are very dependent on experimental work. We don't generate the original data ourselves—we analyze and build models based on experimental data. That means the quality of computational work depends heavily on the quality of the underlying experimental datasets. People often say “garbage in, garbage out.” If the experimental data is poorly annotated or incomplete, the computational predictions will not be reliable. This is why sharing experimental data—and annotating it well—is so important. Yamina Berchiche: You also mentioned the importance of collaboration between experimental and computational researchers. Charlotte Crauwels: Yes, absolutely. I always encourage computational scientists to find experimental collaborators. When you collaborate across disciplines, you create a feedback loop. Computational models generate predictions, experimentalists test them, and the new data helps refine the models. It also makes research more dynamic and motivating. You feel that your work contributes directly to someone else’s experiments. Yamina Berchiche: Let’s talk about your PhD project. What was the core idea behind your research? Charlotte Crauwels: The goal of my PhD was to develop a computational pipeline that supports the design of hybrid—or chimeric—GPCRs. A hybrid GPCR is a receptor constructed by combining elements from two different receptors. Typically, you take a well-characterized GPCR and combine it with a poorly characterized receptor. For example, you might take the extracellular and transmembrane domains of the beta-2 adrenergic receptor and combine them with intracellular loops from an orphan GPCR. This allows researchers to activate the receptor using a known ligand while observing the signaling behavior of the poorly characterized receptor. Yamina Berchiche: So you can essentially probe the signaling pathways of receptors that are otherwise difficult to study. Charlotte Crauwels: Exactly. These hybrid constructs allow researchers to investigate signaling pathways, structural determinants of receptor activation, and even help resolve receptor structures. But designing these hybrids is difficult. Some receptor combinations work very well, while others fail—even when the receptors are very similar. My work focuses on building a computational framework that generates many possible hybrid designs and evaluates them in silico. The system ranks candidate constructs and suggests the most promising ones for experimental testing. Yamina Berchiche: That seems much more efficient than testing dozens of constructs experimentally. Charlotte Crauwels: Yes, that’s the idea. My goal is simply to provide a tool that helps experimental scientists prioritize which constructs to test first. Yamina Berchiche: You also built a database during your PhD. Charlotte Crauwels: Yes. One of the challenges I faced early in my PhD was collecting data on previously published chimeric GPCR constructs. The terminology used in the literature is inconsistent. Some papers call them hybrid receptors, others call them chimeric receptors, and sometimes they’re just described as constructs. It took over a year to gather and curate the data. We eventually created a publicly available database called GPCR ChimeraDB , which collects known hybrid GPCR designs and links them to structural and sequence information. Yamina Berchiche: Let’s switch to a more personal question. What advice would you give to scientists entering computational GPCR research? Charlotte Crauwels: First, dare to ask. People are often more willing to help than we think. Ask to attend conferences, ask for collaborations, ask questions. Second, don’t stay in your bubble. Computational scientists can easily become isolated. It’s important to attend workshops, meet experimental scientists, and keep the broader research context in mind. Yamina Berchiche: Final question. What comes next after your PhD? Charlotte Crauwels: I’m not completely sure yet. But I would be very happy if I can continue working on GPCRs in some way. I feel like I’m just starting to understand how research works. After several years of learning and making mistakes, you finally feel ready to take on bigger questions. So whether it’s in academia or industry, I hope to continue doing research related to GPCR biology. Yamina Berchiche: Charlotte, thank you so much for joining the podcast. It was a pleasure speaking with you. Charlotte Crauwels: Thank you. It was very fun. Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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<< Back to podcast list Strategic Partner(s) Dr. Kenneth A. Jacobson About Dr. Kenneth A. Jacobson Kenneth A. Jacobson received his BA in Liberal Arts from Reed College in 1976 and his Ph.D. in Chemistry from the University of California, San Diego in 1981. He completed postdoctoral training at the Weizmann Institute. In 1983, he joined the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health, in Bethesda, MD. He is currently the Senior Investigator and Chief of the Molecular Recognition Section, Laboratory of Bioorganic Chemistry. He adapts interdisciplinary approaches (synthesis, modeling, pharmacology) to study G protein-coupled receptors (GPCRs) and purinergic signaling and now has four compounds in clinical trials. He has published more than 800 scientific publications, with an H-index of 115. His numerous awards include: 2008 Sato Award; 2009 Medicinal Chemistry Hall of Fame (American Chemical Soc.); 2014 Goodman and Gilman Award; 2017 Tu Youyou Award; 2017 Smissman Award; 2023 Hershberg Award. Dr. Kenneth A. Jacobson on the web NIDDK Web of Science Google Scholar LinkedIn Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Peter Robert Banks About Dr. Peter Robert Banks Peter Banks is currently the Scientific Director at BioTek Instruments , now a part of Agilent . His responsibilities include the management of the company’s applications team and providing scientific guidance to the senior management team on new technology and emerging trends impacting life sciences. Before joining BioTek in 2008, Banks was employed by PerkinElmer for a decade. These roles included management of PerkinElmer’s BioPharma R&D program and Chair of the company’s Scientific Advisory Board. Prior to experiences at PerkinElmer and BioTek, Banks was an Assistant Professor in Analytical Chemistry at Concordia University, Montreal, Canada from 1994 to 1998. Dr. Peter Robert Banks on the web LinkedIn Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Rosie Dawaliby About Dr. Rosie Dawaliby "I’m an expert in early-stage drug discovery, targeting membrane proteins, especially GPCR. I have 10 years of experience in the development and management of R&D projects and teams in the field of pharmacology, in prestigious academic laboratories as well as in biopharmaceutical companies in Europe and the United States. I hold a Ph.D. in Life Sciences from the University of Lausanne, Switzerland, Department of Biochemistry (2005-2009), where I started working on membranes and membrane protein biochemistry by studying membrane fusion and autophagy in yeast and mammalian cells. I have developed my expertise in the field of pharmacology and biochemistry of GPCR and the crucial role of the lipidic environment on their structure and function during my post-doctoral work (2010-2015). This joint project between prof. Brian Kobilka's lab at Stanford University and the SFMB laboratory at the Université Libre de Bruxelles (ULB) resulted in the first systematic study of phospholipid's effect on GPCR conformation and function. In 2016, I joined a company that specialized in therapeutic candidate discovery targeting GPCR ( Confo Therapeutics ) as a team and project leader for antibody discovery for metabolic and inflammatory diseases. I developed G.CLIPS biotech's innovative technology as a synthesis of the different knowledge, experiences, and know-how from the different stages of my career. Before founding G.CLIPS biotech in June 2020. And since then, my incredible adventure as CEO of this fast-growing company started and is continuing." Dr. Rosie Dawaliby on the web LinkedIn Dr. GPCR Ecosystem G.CLIPS Biotech on the web Website LinkedIn Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Mark Schmeizl About Mark Schmeizl Mark leverages 30 years in various life science laboratories & commercial roles with his network of VC & PE contacts to help senior-level life science executives identify new opportunities. He has successfully built numerous global life science, leadership teams, & works closely with both clients & candidates to understand their unique needs & culture. Mark believes professional placement should be about matching talented people with companies where they will thrive, “when the match is right, the results are astonishing.” Dr. Mark Schmeizl on the web Website LinkedIn Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Explore how GPCR signaling shapes mosquito feeding and mating behaviors with Dr. Laura Duvall. Insights for GPCR researchers and functional assay innovators. << Back to podcast list Strategic Partner(s) Why Mosquitoes Hunt You: GPCR Control of Blood Feeding and Mating This episode features Dr. Laura Duvall, whose research tracks the molecular mechanisms that govern mosquito behavior, focusing on the intersection of neuropeptide signaling and GPCR function. Dr. Duvall discusses her lab’s work dissecting how GPCRs—especially neuropeptide Y (NPY) receptors—regulate innate behaviors such as blood feeding and mating in Aedes aegypti . She shares approaches that combine genetic manipulation (CRISPR-Cas9) and functional behavioral assays, including high-throughput and video-based methods, to reveal these receptors’ roles. The conversation explores translational implications, such as leveraging conserved GPCR pathways to inhibit pathogen transmission, highlighting unexpected links between mosquito and human gut-brain signaling. Dr. Duvall emphasizes the value of model systems and cross-species discoveries in GPCR biology. Listeners interested in GPCR drug discovery, functional assay development, or fluorescence-based assays in behavioral research are encouraged to explore more episodes of the Dr. GPCR Podcast and consider the expanded content on Dr. GPCR University . Why This Matters? How GPCR-mediated neuropeptide signaling dictates mosquito attraction to humans, directly impacting disease transmission. Why the study of conserved receptor pathways enables the development of broadly effective, species-independent vector control strategies. What functional and behavioral assays in mosquitoes reveal about the underlying diversity of GPCR signaling across taxa. How dissecting receptor function in non-neuronal tissues uncovers new parallels to human gut-brain communication. Who Should Listen? This episode is essential for anyone advancing GPCR-targeted research in physiological or behavioral contexts. If you often translate receptor mechanism findings from model organisms to human systems. If you want to expand high-throughput or fluorescence-based assay strategies to non-traditional models. If you are interested in how behavioral outcomes emerge from cell-type-specific GPCR expression and signaling dynamics. If you are considering novel ways to connect molecular pharmacology with organismal phenotype, especially in vector biology or neurobiology. About Laura Duvall Laura Duvall trained in biochemistry and behavioral biology at the University of Pennsylvania. During her PhD with Paul Taghert at Washington University in St. Louis, she investigated neuropeptide control of circadian behaviors in Drosophila , with a specific focus on how GPCR family members orchestrate brain clock cell function. As a postdoctoral researcher in Leslie Vosshall’s laboratory at Rockefeller University, Dr. Duvall pivoted to the Aedes aegypti mosquito, focusing on the molecular regulation of feeding and reproductive behaviors via neuropeptidergic GPCR signaling. In 2019, Dr. Duvall established her laboratory at Columbia University, where she is part of the Department of Biological Sciences and the Zuckerman Institute. Recognized with the Beckman Young Investigator Award, the Klingenstein-Simons Fellowship in Neuroscience, and a Pew Scholarship, she continues to drive efforts to decode how evolutionarily conserved GPCR pathways modulate complex behavioral outcomes. Her research is consistently motivated by uncovering new biological connections that can bridge basic and translational science. Guest on The Web LinkedI n Google Scholar Lab Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Antony Boucard - the scientist who discovered that a cell adhesion molecule and a GPCR share a black widow spider toxin binding site — on adhesion GPCRs, synapse formation, and building a research program where none existed before. << Back to podcast list Strategic Partner(s) Antony Boucard: Adhesion GPCRs and the Molecular Code of Synapse Formation Adhesion GPCRs represent one of the most architecturally complex and least understood branches of the GPCR superfamily. Characterized by extracellular domains exceeding 1,000 amino acids, autoproteolytic cleavage at the membrane, and a near-total absence of characterized ligands, these receptors long resisted the molecular tools that made classical family A GPCRs tractable. Only recently has the field established, with confidence, that adhesion GPCRs couple to G proteins at all. Boucard's laboratory at UNAM in Mexico City sits at this frontier. His research centers on the molecular code governing synapse formation — how adhesion GPCRs, working alongside classical cell adhesion molecules, determine which neuronal partners recognize each other and which synaptic contacts stabilize. The work connects receptor biology to neuropsychiatric disease: addiction, autism spectrum disorder, schizophrenia, bipolar disorder, and cancer. The foundation of this program rests on a serendipitous discovery Boucard made in Thomas Südhof's lab — that a cell adhesion molecule and a GPCR, studied separately for over a decade, both bind alpha-latrotoxin from black widow spider venom, and that together they form an intercellular complex no one had previously described. For Boucard, adhesion GPCRs are not simply a research subject. They are the place where everything he has cared about — biochemistry, cell communication, disease, and the students other institutions overlooked — finally came together. About the Guest Antony Boucard is a biochemist and cell biologist who leads the Boucard Laboratory at the National Autonomous University of Mexico (UNAM) in Mexico City, where he has built one of the only research programs in Latin America focused on adhesion GPCRs. He completed graduate training in biochemistry at the Université de Sherbrooke and his postdoctoral fellowship in the laboratory of Thomas Südhof at UT Southwestern and Stanford University, where he made the initial observation linking cell adhesion molecules and GPCRs through their shared binding to alpha-latrotoxin. His current research programs span synapse formation, addiction, autism, schizophrenia, bipolar disorder, and tumorigenesis, applying cell biology, BRET and FRET assays, microscopy, flow cytometry, and custom protein engineering approaches to probe adhesion GPCR function across physiological and pathological contexts. Scientific Themes of the Conversation Adhesion GPCRs as a distinct receptor class — autoproteolytic architecture, orphan status, and the long-delayed confirmation of G protein coupling The molecular logic of synapse formation and how adhesion molecules encode synaptic specificity in the brain Alpha-latrotoxin from black widow spider venom as an experimental bridge connecting cell adhesion molecules and GPCRs Neuropsychiatric disease through the lens of adhesion GPCR biology — addiction, autism spectrum disorder, schizophrenia, and cancer The structural bottleneck: what cryo-EM cannot yet capture about receptor dynamics at the cell surface Pioneering a research field in an underrepresented scientific ecosystem, and recruiting from communities elite institutions have historically overlooked Key Insights from the Conversation 1. Adhesion GPCRs Were Not Considered Real GPCRs For decades, adhesion GPCRs were assigned to the GPCR superfamily on the basis of their seven-transmembrane topology alone — not because G protein coupling had been demonstrated. Whether they functionally coupled to G proteins remained genuinely open, and for much of the field's history, skepticism was reasonable. Boucard's work on their signaling capacity in the context of synaptic biology sits at this still-resolving frontier, where the biology is catching up to the structural classification. 2. A Forgotten Sample, a First Paper During his graduate studies, Boucard left an enzymatic reaction on his bench over a weekend — called away for army training — and returned to find results that had eluded the lab for months. He nearly discarded the sample. Running it on instinct, he obtained reproducible data that became his first publication. The pattern established there — outcomes shaped as much by openness as by design — has followed him through every phase of his career since. 3. The Black Widow Toxin Nobody Put Together Working in Südhof's lab on cell adhesion molecules, Boucard made a lateral decision: to test whether one of the proteins he was studying might bind to a GPCR he had no reason to investigate. The interaction was real. On a colleague's suggestion, he recognized that both proteins had independently been shown to bind alpha-latrotoxin from black widow spider venom — but no one had ever asked whether they interacted with each other. They formed an intercellular adhesion complex. Südhof himself was skeptical; the field had studied both proteins for over a decade without making the connection. That discovery became the foundation of Boucard's independent research program. 4. Adhesion GPCRs Open a Pandora's Box Adhesion GPCRs appear across nearly every biological process — from embryonic development to synaptic maturation, from immune cell trafficking to tumorigenesis. Boucard describes this breadth not as an opportunity but as a constraint: the challenge for his lab has been choosing which processes to study rigorously rather than chasing the full landscape. Anchoring the work in synapse formation provides a tractable and biologically meaningful lens, while the transversal logic — that what is learned about adhesion in one context often illuminates another — keeps the research portfolio coherent. 5. The Structural Bottleneck Cryo-EM has transformed understanding of classical GPCR structure, but adhesion GPCRs remain dramatically underrepresented in the structural database. The deeper issue, Boucard argues, is not just the quantity of structures but their nature: every cryo-EM image is a frozen moment, capturing a receptor in one state, in one membrane environment, at one point in time. What the field still cannot do is observe the dynamics of receptor assembly, complex formation, and signaling in real time at the cell surface. That gap is where the most important biology is happening. 6. Choosing Mexico City as a Scientific Bet After postdoctoral and faculty positions at Stanford and UT Southwestern, Boucard surveyed the conventional research markets — North America, Western Europe — and concluded that his skills were not especially scarce there. Mexico City offered something different: a research territory in adhesion GPCR biology that was entirely unoccupied, a massive university drawing students from across Latin America and indigenous communities within Mexico, and a scientific culture where his particular combination of biochemistry, cell biology, and translational thinking could do something that wasn't already being done. Eight years in, he has not reconsidered the decision. Episode Timeline Timestamps were generated with AI assistance from the episode transcript and may not reflect exact segment boundaries. Use them as navigational guides. 00:00 Sponsor intro — GeneTex & Eurofins DiscoverX 00:43 Introducing Boucard: a scientific path that was never planned 01:40 From biochemistry by accident: Sherbrooke, Dallas, Stanford, Mexico City 03:43 The summer lab that changed everything — and why he turned down medical school 10:23 Army service, social work in Nicaragua, and the civil war that reframed resources and risk 16:18 Turning down the medical school acceptance — 25 years of no regrets 22:10 Université de Sherbrooke's industry-integrated curriculum and what it modeled about flexibility 26:06 Surviving crisis in Haiti and what scarcity teaches about choice 31:33 The underground restaurant in San Francisco, born out of an immigration emergency — and Chef's Table Season 2 43:45 Time, focus, and the discipline of 15 minutes a day 52:38 Why Mexico City: building a lab for students no one else was recruiting 01:00:00 Adhesion GPCRs — the receptor family that kept calling him back 01:04:58 The black widow toxin discovery — two proteins, 15 years of prior research, one untested pair 01:06:18 Why adhesion GPCRs are among the hardest receptors to work with, and why structures are finally coming 01:09:10 Synapse formation, addiction, autism, schizophrenia, and cancer: the lab's research logic 01:13:45 Assays: BRET, FRET, microscopy, flow cytometry, and engineering membrane-anchored ligands into solution 01:19:29 The dream tool — a nanoscale camera navigating the cell surface in real time 01:22:24 Advice to junior scientists: don't be afraid to be afraid 01:26:00 Three aha moments: socks, a forgotten sample, and one cold email to a Nobel laureate 01:35:33 Lab openings and where to find the Boucard Lab Selected Quotes "Every single one of my days right now has been just to reconstruct what I learned the day before. That's something that I really love — you kind of put yourself in the mindset of the kid once again." "A lot of people say there's a lot of reasons not to do an experiment. There's a ton. But sometimes you can just do one. And you never know." "I can't believe you won the Nobel Prize. Because at home, he can't even pick up his own socks." — Said to Boucard by a fellow Nobel laureate's wife, at a ceremony at Stanford, following the 2013 prize announcement "If you willingly put yourself in a situation where you're willing to take risks, things will fall into place. But if you never try, you might not know. And whether you're there for a short time or for the rest of your life, you'll have the best time of your life during the time you're doing it." About Dr. Antony A. Boucard Jr. Dr. Antony Boucard joined the Université de Sherbrooke (Québec, Canada) as a B.S. student of the Biochemistry program in 1994 from which he graduated in 1997. It is then that his interest bloomed for the study of GPCRs while joining the group of Dr. Richard Leduc and Dr. Gaetan Guillemette in the Pharmacology department at the Université de Sherbrooke. He completed a master’s degree in 2000 and a Ph.D. degree in 2003 with a particular interest in the cardiovascular system by investigating the structure of the Angiotensin and Urotensin receptors through various biochemical approaches centered in the elucidation of ligand binding pocket determinants. Motivated by a new ambition to study the nervous system, Dr. Boucard pursued postdoctoral training at the University of Texas Southwestern Medical Center in Dallas where he joined the group of Dr. Thomas Südhof . In this institution dear to the heart of GPCR enthusiasts given that its faculty personnel included Dr. Alfred Gilman , Nobel Laureate for his discovery of G proteins, Dr. Boucard ventured into the field of synaptic adhesion molecules which would eventually prompt him to investigate the role of a peculiar family of GPCRs belonging to the Adhesion subgroup. After a relocation to Stanford University where he pioneered work on ligand discovery for then orphan adhesion GPCRs, Dr. Boucard moved to Mexico City to establish himself as an independent investigator integrating the department of Cell Biology at the Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN). Dr. Boucard´s lab focuses on molecular and cellular mechanisms underlying the function of adhesion GPCRs in the formation of synapses. Having a particular interest for a three-member family named latrophilins, his lab seeks to decipher the molecular code instructing adhesion events mediated by these GPCRs. The pharmacology of latrophilins brings about a great deal of challenges given that they are highly polymorphic proteins expressed as various alternatively spliced isoforms thus potentially resulting in differential modulation of cell signaling pathways. His lab highlighted the importance of splicing events in biasing latrophilins’ regulation of cyclic AMP pathways and for determining the magnitude of ligand selectivity. Additionally, his team is also interested in understanding the pathophysiological relevance of latrophilins’ function in neuropsychiatric disorders given their association with genetic susceptibility to the neurodevelopmental disorder known as attention deficit hyperactivity disorder (ADHD) but also to a comorbid clinical manifestation linked to addiction. He also actively volunteers as an Associate Professor of the non-governmental organization Institut des Sciences, des Technologies et des Etudes Avancées d’Haïti (ISTEAH) to help consolidate higher education in Haiti. Dr. Antony A. Boucard Jr. on the web Website LinkedIn Researchgate Loop Academia Pubmed Adhesion GPCR Consortium University of Haiti Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Access expert CRO advisory services through the Dr. GPCR Ecosystem. Get guidance, strategies, and insights to optimize your GPCR research and drug discovery projects. Home About Services News Get in Touch Welcome CRO & Vendor Advisory Your Science Is Strong. Your Process Should Be, Too. I help CRO teams bring structure to collaboration—so your data gets acted on, not overlooked. When biotech partners trust your process, they come back again and again. You deliver high-quality data. But when timelines shift, expectations blur, or feedback loops break down, even the best work can lose momentum. Let’s turn your scientific rigor into results that move programs—and people—forward. Power My Discovery Biotech Clients Want Results - Not Confusion Every CRO I work with has great science—but clients still struggle to understand the value. Here's what I hear from biotech teams: “We’re not sure what we’re getting—or when we’re getting it.” “The science is solid, but the communication is scattered.” “The data looks fine, but it doesn’t help us make decisions.” Great science isn’t enough if clients don’t feel aligned, informed, and in control. That’s where I come in. How I Help CROs Deliver High-Impact Science That Biotech Teams Trust Biotech Clients Stay in Sync With Your Team I work to strengthen communication & collaboration: • Facilitate smoother communication between technical teams and biotech clients • Set clear expectations and deliverables to build trust and reduce delays • Align teams across roles—from assay execution to client updates Data Turns Into Decisions—Not Delays I help turn great science into clear deliverables • Define program objectives and guide assay plans that support partner decisions • Translate discovery data into clear, actionable formats biotech teams can use • Streamline deliverables to reduce review cycles and accelerate go/no-go calls & shorten timelines Your Science Stays Focused on What Matters We work together to position your CRO for growth • Refine your offering to match what biotech teams actually need • Position your services to shorten sales cycles and increase repeat business • Turn client feedback into improvements that boost trust and outcomes Here's What CROs Are Saying "Before working with Yamina, we were generating high-quality data across biotech programs but often navigating evolving expectations and goals from different stakeholders. After partnering with her, communication became clearer, deliverables were better defined, and collaboration across teams ran more smoothly. She helped streamline complex projects and made the CRO–client relationship more effective and productive." - Anne Marie Quinn, CEO Montana Molecular Frequently Asked Questions 01 What kinds of CROs do you work with? Any CRO focused on GPCRs, pharmacology, discovery biology, or antibody discovery—regardless of size or location. 02 What happens when I reach out? We'll start with a focused conversation about your programs and current challenges. You'll leave with clarity—even if we don't end up working together. 03 Can you help on an ongoing basis? Yes. I offer both short-term consulting and ongoing partnerships depending on your needs. Power My Discovery Send me a message First name* Last name Company name* Email* How Can I Help?* Send Message or Book My Call Menu Home Services About Ready to collaborate? Let’s talk about how I support GPCR discovery, pharmacology strategy, and cross-functional execution across biotech, VC, and CRO teams. Get in touch Connect LinkedIn Podcast Dr. GPCR Calendly ©2023-2025 All rights reserved by FindYooour, LLC & Dr. GPCR Corp Proudly created with Wix.com

Discover how Timeline Strategy helps GPCR innovators scale their organizations through strategic planning, effective systems, and operational clarity. Home: Welcome Timeline Strategy x Dr. GPCR — Scaling Biotech Beyond the Bench Turning scientific excellence into scalable organizations. We help GPCR innovators design systems, strategies, and operating frameworks that drive predictable growth. See how we can help you About Timeline Strategy Founded by Attila Foris, Timeline Strategy partners with science-driven teams to bridge the gap between innovation and execution. Our work helps biotech startups, research organizations, and CROs design operating systems that enable clarity, accountability, and scale. Core themes: Strategic Planning for Biotech Growth Operational System Design (OS) Cross-functional Team Alignment Scaling Protocols & Decision Architecture From Chaos to Scale Timeline Strategy built to execute, not decorate slides Most strategies die in PowerPoints. Timeline Strategy lives in execution. In 3 fast steps , we turn your bottlenecks into momentum: 1. Diagnose the mess → where your growth stalls. 2. Build clarity → align people, process, priorities. 3. Scale with confidence → expand without burnout. Building the Strategic Backbone of GPCR Innovation In the rapidly evolving GPCR field, scientific progress alone isn’t enough — sustainable growth requires operational precision. Together with Dr. GPCR, we help organizations: ✅ Clarify vision and direction ✅ Translate research milestones into measurable objectives ✅ Build internal systems and workflows that support scale ✅ Create investor-ready operating structures Our Partners Benefit From: Strategy Audits & Growth Frameworks Operating System (OS) Implementation Leadership Alignment Sessions Scalable Team Protocols & Processes From the Strategy & Operations Blog The Hidden Cost of Ambition in Biotech Leadership 👉 Ambition is the default setting of biotech. Platforms expand. Indications multiply. New opportunities appear constantly. That is not a flaw. It is the nature of scientific possibility. 👉 The problem begins when ambition grows faster than structure. What feels like momentum can quietly become dilution. More programs. Broader roadmaps. Increasing complexity. And slowly, strategic focus weakens . This is the hidden cost of ambition in biotech leadership. Not failure. Not poo Attila Foris Mar 2 The Real Cost of Strategic Overload in Biotech 👉 In early-stage biotech, activity often feels like strategy. The platform is advancing, multiple indications are progressing, a grant application is underway, and early partnership conversations are taking shape. At the same time, the team is preparing for biotech fundraising. On the surface, this looks like a strength. There is movement across the board. Each initiative has logic behind it. Each program appears to increase optionality and reduce risk. 👉 This is where str Attila Foris Feb 23 The Moment Biotech Founders Realize the Money Is Gone 👉 Most biotech founders do not realize they are in trouble when the money runs out. By then, the situation is already decided. 👉 The real issue begins earlier, at a point where the company is still operating, the science is progressing, and milestones are being met. On paper, things look fine. In reality, something more subtle starts to shift. 👉 Decision-making changes. Plans that once felt flexible start to feel constrained. Conversations move from options to assumption Attila Foris Feb 16 1 2 3 4 5 Collaborate with Timeline Strategy Whether you’re leading a GPCR startup, a CRO, or an academic lab ready to scale, Timeline Strategy helps you design clarity into your growth process.

Discover the essence of GPCR Retreat, an international GPCR Event that empowers the GPCR field. GPCR Reatreat The GPCR Retreat focuses on advances in our understanding of how GPCRs operate in cell communication. The main goal of the GPCR Retreat is to provide a venue for students, post-doctoral fellows, and principal investigators from academia and industry to discuss and debate existing and novel concepts in GPCR biology. One of the core values of this international meeting is to promote interactions among all participants of all diversity backgrounds, particularly between trainees and principal investigators. Each year, approximately 2/3 of the participants are trainees. Registration to the GPCR Retreat is capped at 200 participants to promote an intimate environment. Most importantly, the GPCR Retreat dedicates time for two trainee symposia, an initiative that began in the Ottawa 2017 edition, to showcase the breadth of diversity in GPCR trainee communities. For the Ottawa 2017 GPCR Retreat, of the ten talks from trainees 80% were from women and 60% from visible minorities. Over the years, the meeting has grown into one of the most recognized international events in the field. That reputation has led to broad participation from the Great Lakes region and beyond. Conference History The GPCR Retreat is an annual joint meeting with the Club des récepteurs à Sept Domaines Transmembranaires du Québec that rotates around locations in Canada and the United States surrounding the Great Lakes region. The first Great Lakes GPCR Retreat was conceived, organized and held in London, Ontario, Canada in October 1999. The following year, the Great Lakes GPCR Retreat partnered with the annual symposium of the Club des Récepteurs à Sept Domains Transmembranaires du Québec. The meeting tours through many of the major universities in the Great Lakes region in both Canada and the United States. The past few GPCR retreats have been held in: - Niagara-on-the-lake (2022) - Bromont, Québec (2019) - Detroit, Michigan (2018) - Ottawa, Ontario (2017) - Chicago, Illinois (2016) - Toronto, Ontario (2015) - Bromont, Québec (2014) - Cleveland, Ohio (2013) London, Ontario (2012) Fairmont Le Château Montebello, Québec, Canada November 2-4, 2023 We are pleased to welcome you at Le Château Montebello, the 22nd Annual Great Lakes G Protein-Coupled Receptor Retreat held jointly with the Club des Récepteurs à Sept Domaines Transmembranaires du Québec. The meeting will be held on Nov. 2-4, 2023 at the Chateau Montebello, Québec. The Chateau Montebello is an exceptional venue, and is located 1 hr from Ottawa, or 1.5 hr from Montreal in the beautiful Laurentian Mountains of Canada. The fall colors of the leaves are spectacular, and the weekend of science is an intense and interactive experience, and a great training environment for our students and post-doctoral fellows. The meeting is launched on Thursday with two Trainee Symposia and the Plenary Lecture, followed by 6 symposia on Friday and Saturday and the closing Keynote Lecture. The deadline for registration is September 21, 2023. For the 22nd edition, the Organizing Committee has again lived up to the expectations by putting together an outstanding program with a special thought for Marc Caron (1946-2022) to commemorate his great contributions to the GPCR and Neurosciences fields. Dr. Kathleen Caron of the University of North Carolina at Chapel Hill, unquestionably one of the pioneers involved in deciphering how receptor activity-modifying proteins or RAMPs regulate GPCR function, is confirmed as Plenary Speaker of the inaugural Marc G. Caron keynote lecture on November 2nd. Additionally, there will be a Marc G. Caron Honorary Symposium by Caron Lab alumni to honor his memory. We have also confirmed Dr. Arthur Christopoulos of Monash University in Australia, one of the pioneers in the medicinal chemistry, computational and mathematical modelling of GPCRs, as Plenary Speaker of the Hyman B. Niznik keynote lecture, which will close the conference. The program will include also world-class and diverse GPCR scientists working in the arenas of structure and signaling, neuroscience, cancer, translational and model systems. As in previous editions, trainees are more than welcome to this unique meeting. Indeed, for the Montebello 2023 edition, we have organized two trainee symposiums to acknowledge formally the participation of our graduate students and post-doctoral fellows. Additionally, each symposium of the GPCR Retreat 2023 will include one trainee short talk selected from abstracts. Trainees of diversity groups are strongly encouraged to register to the meeting and submit an abstract for consideration for the trainee symposia and selected trainee short talks. Your participation has already made this unique event a success. We are thrilled by the overwhelming interest in this event by the GPCR research community. We trust that the collegial and intimate atmosphere provided by Le Château Montebello will be suited for an environment where graduate students, postdoctoral fellows and principal investigators can have stimulating discussions and debates on GPCR research presented at this meeting. We would like to thank all our Sponsors for their ongoing generous support of the meeting. Without their support, this meeting will not be possible. If you have any suggestions or comments for either this Retreat or future meetings, we look forward to receiving your feedback. Finally, Bienvenue and we hope you will enjoy your stay in Montebello and find the Retreat stimulating and satisfying. Sincerely, The Organizing Committee GPCR Retreat Organizers

Share your thoughts and help shape the future of the Dr. GPCR Ecosystem. Your feedback guides improvements, new features, and community resources. Dr. GPCR Community Survey Help us build the next evolution of the GPCR Ecosystem — together. Every opinion counts. Whether you’ve joined our University sessions, explored our Job Board, or attended a Happy Hour, your feedback shapes what comes next. Let’s make Dr. GPCR more useful, connected, and inspiring for everyone in the field. 👉 Take the Survey Now Why Your Feedback Matters? We’re growing — and your input helps us grow in the right direction. By sharing your thoughts, you directly influence how we design new features, events, and educational programs. Your responses help us: Improve the Dr. GPCR University curriculum and resources. Make Retreats and Happy Hours more valuable and accessible. Build stronger connections between academia and industry. Develop new tools, training programs, and mentorship programs tailored to your specific needs. Your Voice Shapes Our Future Dr. GPCR was founded to bring the GPCR community together — and every survey response helps us strengthen that mission. This isn’t just a form — it’s how you influence the next generation of education, collaboration, and discovery. 💡 Start the Survey What We’d Love to Learn? We’ve grouped the questions into three sections so your feedback can make a real impact: 1. Your Experience How often do you use the Dr. GPCR platform? Which programs do you engage with most? (University, Retreat, Job Board, Newsletter, etc.) What has been your favorite experience so far? 2. Your Needs What topics or training modules would you like us to add next? What challenges do you face most in your research or biotech journey? How can we facilitate easier collaboration within the community? 3. Your Feedback How likely are you to recommend Dr. GPCR to a colleague? (1–10) What would make your experience even better? Any ideas, suggestions, or features you’d love to see in 2026? Survey 🙏 Thank You for Being Part of the Ecosystem Your feedback helps us: Keep events free or affordable Expand our shared knowledge base Support students and researchers entering the field Together, we’re building a home for everyone passionate about GPCR research and innovation.

<< Back to podcast list Strategic Partner(s) Dr. Davide Calebiro About Dr. Davide Calebiro "Davide Calebiro is Chair of Molecular Endocrinology and Wellcome Trust Senior Research Fellow at the Institute of Metabolism and Systems Research (IMSR) of the University of Birmingham and Co-Director of the Centre of Membrane Proteins and Receptors (COMPARE) of the Universities of Birmingham and Nottingham. He studied Medicine in Milan and Stockholm, and obtained a PhD in Molecular Medicine and a Clinical Specialisation in Endocrinology and Metabolic Disease from the University of Milan. Between 2009 and 2017, he was a Group Leader at the Institute of Pharmacology and Toxicology and Rudolf Virchow Center of the University of Würzburg, Germany. He leads a multidisciplinary research team comprising biologists, chemists, physicists, engineers and computer scientists focusing on the basic mechanisms of G protein-coupled receptor (GPCR) signalling and their alterations in endocrine, metabolic and cardiovascular diseases. To study GPCR signalling, they develop and use innovative optical methods based on FRET and single-molecule microscopy, which allow them to directly observe signalling events in living cells and tissues with unprecedented spatiotemporal resolution. His major scientific contributions include the discovery that GPCRs are not only active at the plasma membrane but also at intracellular sites and that these receptors interact among themselves and with other membrane proteins to form dynamic nanodomains at the plasma membrane. Davide’s work has been published in prestigious scientific journals such as Nature, Cell, New England Journal of Medicine, Journal of Clinical Investigation, PLoS Biology, PNAS, Nature Communications and Science Advances, attracting several prizes and awards. He has served on multiple panels and committees, including the ENDO Annual Meeting Steering Committee and the MRC Molecular & Cellular Medicine Board." Dr. Davide Calebiro on the web University of Birmingham Twitter Google Scholar LinkedIn Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Can models predict drug outcomes? Jens Carlsson shares how GPCR modeling is moving from explanation to real prediction in drug discovery. << Back to podcast list Strategic Partner(s) Model. Predict. Discover. with Dr. Jens Carlsson What if models didn’t just explain the past — but could truly predict what comes next? In this episode, Dr. Jens Carlsson reveals how computational modeling is evolving from explanation to real prediction—and how that shift accelerates real-world discovery. Dr. Jens Carlsson, Professor of Computational Biochemistry at Uppsala University, joins Dr. Yamina Berchiche to share his unconventional journey from aspiring engineer to GPCR modeler. With a deep focus on structure-based drug design, Jens discusses how his lab bridges simulation and experiment—and why understanding the limits of prediction is just as critical as the predictions themselves. From virtual screening of billions of molecules to leveraging AlphaFold for structure prediction, Jens shares the cutting-edge tools his lab uses—and the collaborative mindset required to turn models into testable hypotheses. Along the way, he reflects on key career moments, the role of mentorship, and how curiosity continues to drive his work across both academic and industry settings. Why This Matters Computational models are moving beyond interpretation into real-world prediction of ligand-receptor interactions. Bridging computation, chemistry, and pharmacology is key to speeding up drug discovery. AI and machine learning are opening new doors—but only if scientists know their tools’ limits. What You’ll Learn Why Jens Carlsson believes modeling should predict , not just explain How his team uses structure-based modeling to identify novel GPCR ligands The value of failure—and how it shaped his path as a scientist Why collaborations between modelers and experimentalists are more vital than ever How AlphaFold is shaking up structural biology—and where it still falls short Advice for junior scientists: what really matters when building a research career Who Should Listen GPCR scientists and pharmacologists Computational chemists and structural biologists Early-career researchers exploring drug discovery Biotech leaders and R&D strategists Anyone interested in predictive modeling, AI in biology, or structure-function relationships About Jens Carlsson Jens Carlsson is a Professor of Computational Biochemistry at Uppsala University, where his research group uses structure-based modeling to investigate GPCRs. His team focuses on understanding how ligands modulate receptor function and how those insights can drive drug discovery. By combining molecular docking, molecular dynamics, and machine learning, Jens works at the intersection of computation and pharmacology, often in close collaboration with experimental labs. Trained initially as a biotechnology engineer, Jens discovered his true calling during an internship where his modeling skills stood out, mainly because his bench skills didn’t. That moment launched a career built around using computational tools to answer big biological questions. His journey took him from Sweden to Scripps Research and UCSF, where he was first introduced to GPCRs and mentored by pioneers like Brian Shoichet and Ken Jacobson. Jens is passionate about prediction over explanation: building models that can guide experiments, not just interpret them. Outside academia, he advises companies through a consulting arm focused on ligand design strategy. With a reputation for collaborative science, Jens is a strong advocate for bringing together chemists, modelers, and biologists to accelerate discovery and train the next generation of GPCR researchers. Jens Carlsson on the web Carlsson Group Uppsala University LinkedIn Hit play now to hear how prediction is reshaping GPCR science, and what that means for the future of drug discovery. Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Your One-Stop-Shop for GPCR Drug Discovery and Development Researchers developing GPCR-targeted therapeutics need a reliable, comprehensive partner that spans discovery, optimization, and regulatory submission. Eurofins DiscoverX leads GPCR research innovation with 25+ years of expertise and provides you with product solutions including cell-based assays for basic research through therapeutic discovery and development. The assays are validated and accepted by industry and the scientific community, with thousands of peer-reviewed publications and billions of data points screened. These industry-standard assays, designed for regulatory submissions, are backed by partnerships with leading pharma and biotech companies worldwide. 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This comprehensive portfolio offers multiple product formats to match your exact needs, whether you're conducting exploratory screens or regulatory-compliant potency testing. Assay Principle of Eurofins DiscoverX Cell-based Assays Whether you are developing small-molecule or biologic therapeutic drugs, Eurofins DiscoverX provides you with a variety of drug discovery and development products with multiple assay types and applications to meet your specific GPCR research needs. Access Product Solutions and Key Resources GPCR Functional Cell-Based Assays - Assessing Biased Signaling of Agonist Access White Paper Discover Your GPCR Solution - Find The Assay for Your Target of Interest Find Your Solutions The Human GPCRome - Obtain Your FREE Wall Poster for Your Laboratory Obtain Wall Poster Access GPCR Cell Line Assays, Ready-to-Use Kits, Mem Preps, & More Shop Products Supporting GPCR-focused Obesity and Diabetes Research Eurofins DiscoverX supports the ongoing obesity/diabetes revolution with the most comprehensive, validated portfolio for obesity and diabetes GPCR targets, including GLP-1, GIP, GCG, MC4, PYY, AMY receptors, and more. Browse products related to your obesity/diabetes target of interest: CALCRL and RAMP (AMs) GIPR GLP-1R GLP-2R GCGR GPR75 MC4R NPY2R (PYY) SSTR5 Activins CALCR and RAMPs (AMYs) Apelin (APJ/AGTRL1) View representative data: GLP-1R multi-MOA profiling Eurofins DiscoverX's GLP-1 receptor (GLP-1R) assay portfolio illustrates a comprehensive approach to obesity research, with complete MOA coverage for a single target: GLP-1. These assays enable complete pharmacological profiling across cAMP, β-arrestin, and internalization. GLP-1R representative assay results (dose-response curves) for exendin-4, tirzepatide, and retatrutide. A. cAMP dose–response; B. β-arrestin recruitment showing ligand bias; and C. Internalization profiles distinguishing highly versus weakly internalizing agonists. Together, these datasets exemplify the depth of pharmacological insight enabled by Eurofins DiscoverX platforms. This multi-dimensional characterization extends across our full obesity and diabetes product portfolio, including GIPR, GCGR, AMY receptors, MC4R, and beyond. Access GPCR Obesity and Diabetes Solutions and Key Resources Discover GPCR Obesity and Diabetes Product Solutions Find Your Solution Review GIP Product Solutions to Support Obesity/Diabetes View GIP Solutions Explore GLP-1 Product Solutions to Support Obesity/Diabetes See GLP-1 Solutions Accelerating Obesity Therapeutics Development Download App Note Beyond Eurofins DiscoverX Products: The Full Power of Eurofins Discovery Eurofins DiscoverX cell lines, assays, kits, and custom product solutions represent the foundation of tools for GPCR research and drug discovery and development. When these product solutions are combined with Calixar GPCR membrane proteins and Eurofins Discovery GPCR services, the benefits from integration provide the most comprehensive GPCR research and drug discovery platform spanning the entire discovery and development continuum. Eurofins Discovery GPCR services provides the industry's most extensive collection of validated GPCR assays with hundreds of binding and functional assays, available individually or in panels. These assays use the same platform as the Eurofins DiscoverX assays and beyond. Calixar GPCR membrane proteins , as a service, provides a wide array of GPCRs from various species, purified to the highest standards to ensure purity, integrity, and biological activity. These GPCRs are excellent for use in functional, structural, or identification assays. Let us Help You Get Started! Contact us Visit GPCR Product Solutions

Equip your research team with expert-led GPCR pharmacology training. Get 25% off Annual Premium Memberships for teams of five or more. Activate in days. Home Courses Articles About Log In / Sign Up Equip Your Team with Terry Kenakin’s Pharmacology Frameworks Used by discovery scientists across biotech, pharma, and academia. Shared pharmacology discipline for discovery teams. When scientists interpret pharmacology through the same frameworks, experiments become clearer and program decisions become stronger. Train 5 or more team members and receive 25% off annual access. $2,249.25 per person / year Activate Team Membership Why Teams Use Terry’s Corner Discovery programs move faster when scientists interpret pharmacology through the same mechanistic frameworks. Terry’s Corner helps teams align how they analyze receptor pharmacology, signaling data, and translational outcomes. That alignment reduces misinterpretation and improves experimental strategy across programs. What Your Team Gets? • Pharmacology frameworks used in modern drug discovery • Monthly live AMA discussions with Terry Kenakin • Ongoing Terry’s Corner lessons and analysis • Ability to suggest topics relevant to your programs • Access for biotech, pharma, and academic discovery teams • Full Dr. GPCR University Premium access for every team member How Team Membership Works? 1 — Prepare Your Team Gather at least 5 scientists who will participate. Each participant must have a Dr. GPCR Ecosystem account . 2 — Submit Your Team Details Provide names, emails, and organization information so we can activate access correctly. 3 — Complete the Payment Secure your team membership and receive confirmation. 4 — Membership Activation Our team activates all seats and confirms access. Activation typically takes 3–10 business days . Need to add members later? Our team can help expand your membership anytime. Apply for Team Membership First name* Last name* Email* Company name* Company Website* Names & Emails of Each Team Member (minimum 5)* Team Size* Annual Premium Team access. Minimum five seats. Priced per person per year. $2,249.25 Order Now 💡 Have questions? Contact us at Hello@DGPCR.org Terry’s Pharmacology Corner — Created by Dr. Terry Kenakin , powered by Dr. GPCR . Stay connected on LinkedIn and YouTube . Explore : Foundational Lessons — Build Your Pharmacology Core Emerging Drug Hunter — Expand Your Edge Expert-Level Mastery — Advanced Pharmacology Live AMA Sessions with Terry

Masha Niv on bitter taste GPCRs, the drug bitterness blind spot, and what heavy water reveals about the sweet taste receptor. << Back to podcast list Strategic Partner(s) Masha Niv: Bitter Taste Receptors and the Drug Discovery Blind Spot Taste receptors are among the most overlooked GPCRs in pharmacology - and Masha Niv has spent her career building the tools to change that. This conversation explores the biology, diversity, and unexpected reach of human taste GPCRs, beginning with the 25-subtype family of bitter taste receptors and extending into sweet receptor signaling, extraoral tissue expression, and the emerging science of taste-based drug prediction. Niv describes how bitter taste receptors differ structurally from most other GPCRs - missing conserved motifs, more prone to activation, and resistant to pharmacological blockade - and why those properties have shaped both the therapeutic opportunities and the research challenges her lab works on. She traces the receptor-ligand matchmaking problem at the heart of the field: 25 subtypes, thousands of known bitter compounds, and a network of associations that a machine learning recommendation system is now beginning to map. The conversation also covers what happens when taste pharmacology intersects with drug development - a collision that, for most of pharmaceutical history, has occurred too late. Niv's early exposure to bitterness as a formulation problem rooted her work in a question that still matters every time a patient refuses a pill. ABOUT THE GUEST Masha Niv is associate professor and vice dean of research and development at the Hebrew University of Jerusalem's Faculty of Agriculture, Food and Environment, located in Rehovot. A computational pharmacologist by training, she built BitterDB - the first dedicated database of bitter compounds - and has mapped the structural and chemical properties governing ligand promiscuity across all 25 human bitter taste receptor subtypes. Her lab uses homology modeling, machine learning, and collaborative sensory experiments to predict bitterness, identify antagonists, and understand how taste GPCRs function in tissues far from the tongue. She was also a key contributor to the GCCR consortium's large-scale chemosensory research during the COVID-19 pandemic. SCIENTIFIC THEMES OF THE CONVERSATION The architecture of bitter taste receptor diversity - 25 subtypes, ligand promiscuity, and the challenge of orphan receptors with no known ligand Extraoral expression of taste GPCRs - physiological roles in the airways, gut, heart, and cancer tissues Receptor-ligand matchmaking - applying recommendation system logic to the bitter taste receptor family Sweet taste receptor biology and the heavy water paradox - what a single atomic substitution reveals about receptor sensitivity Bitterness as a drug development variable - machine learning prediction, formulation consequences, and the FDA's late entry into the conversation COVID-19 and chemosensory science - how a global consortium formed from a handful of tweets and what it found about taste and smell loss KEY INSIGHTS FROM THE CONVERSATION 1. Bitter taste receptors are built to activate, not to be blocked Bitter taste GPCRs are structurally unusual within the broader GPCR family - they lack several conserved motifs and disulfide bridges present in most other subfamilies. Niv argues this architecture reflects evolutionary logic: a receptor whose job is to detect potential toxins before consumption should be maximally sensitive to activation. The cost is that finding antagonists for these receptors has proven far more difficult than finding agonists, a pharmacological asymmetry her lab is actively working to resolve. 2. Bitterness and toxicity are not the same thing - and the field had to prove it A long-standing assumption in both traditional medicine and drug development treated bitterness as a proxy for toxicity. Niv's work directly challenged that correlation: many intensely bitter compounds are non-toxic, and many toxic compounds are not bitter at all. Recognizing that distinction opened space for a more nuanced view of bitter compounds in nutrition and pharmacology - including the possibility that some bitterness in diet is associated with health benefit, not harm. 3. The drug bitterness blind spot persisted for decades because no one built the right tool early enough Drug discovery workflows screen extensively for efficacy, safety, and pharmacokinetics - but bitterness prediction was rarely incorporated until clinical or even post-market stages. Niv's lab developed a machine learning predictor trained on intensely bitter compounds that can flag bitterness risk from chemical structure alone, early in the development pipeline. The FDA recently made taste reporting a formal requirement, a regulatory shift Niv sees as overdue. 4. A single atomic change in water is enough to activate the sweet taste receptor Deuterated water - in which hydrogen is replaced by the heavier isotope deuterium - produces a measurable sweet signal in sensory experiments. Niv's lab showed that this response depends on the T1R2/T1R3 heterodimer sweet taste receptor: a known receptor inhibitor suppresses the sweetness of heavy water. What makes this finding unusual is the magnitude of the effect relative to the size of the chemical change - the mechanism is still under investigation, but the receptor involvement is established. 5. Taste receptor expression throughout the body reshapes the meaning of drug off-targets Bitter taste receptors are expressed not only in taste receptor cells on the tongue but in the upper airways, gut, heart, and certain cancer tissues. This extraoral distribution has practical consequences: drugs targeting other receptors may be inadvertently activating bitter taste GPCRs in the lung or intestine, contributing to effects that were never attributed to the right target. Niv sees this as one of the more underexplored dimensions of polypharmacology. 6. COVID-19 taste loss was a scientific detour that became something larger Niv had not planned to work on COVID-19 - she had never worked on viruses and was cautious about entering a field she did not know. When reports of taste impairment emerged, she felt obligated to contribute. A small cluster of Twitter exchanges became email threads, became a Slack workspace, became the GCCR consortium - a rapid-assembly international collaboration that surveyed tens of thousands of patients and found that while both smell and taste are impaired in the majority of symptomatic cases, smell loss is the stronger diagnostic signal. 7. The matchmaking problem - and why recommendation systems belong in receptor pharmacology With 25 subtypes, thousands of known bitter ligands, and a matrix of partial associations, the question of which compound activates which receptor is too large and too sparse for classical screening alone. Niv's lab is developing a recommendation system - trained on known receptor-ligand pairs and the structural properties of both - that can suggest candidate receptors for any new compound. The analogy she uses is direct: the system works the way a streaming platform learns your preferences from what similar users have watched. EPISODE TIMELINE Note: Timestamps below are AI-generated from the episode transcript and are approximate. Exact times may vary slightly from the final edited audio or video. 00:00 - Introduction and Dr. GPCR announcements 01:26 - Niv's career path - from theoretical chemistry in Russia and Israel to biotech, then a Cornell postdoc 08:03 - Choosing taste GPCRs as a research focus - how the arrival of GPCR structures made this the right moment 10:49 - The bitter taste receptor family - 25 subtypes, BitterDB, and the receptor-ligand matchmaking challenge 15:53 - Extraoral expression - bitter taste receptors in the airways, gut, heart, and cancer tissues 19:37 - Sweet taste receptors and an unexpected result - heavy water activates the T1R2/T1R3 heterodimer 23:53 - COVID-19 and chemosensory loss - how a global research consortium assembled from a handful of tweets 31:01 - The formulation problem - when a clinically effective drug fails because no one screened for bitterness 38:55 - Why bitter taste GPCRs resist antagonists - structural architecture and pharmacological consequences 41:58 - Taste GPCRs as drug targets - asthma, cardiac physiology, and early signals in cancer biology 44:18 - Rethinking bitterness in nutrition - the case for accepting bitter compounds in Western diet 50:13 - Advice for junior scientists and resources for the GPCR community SELECTED QUOTES "They are more prone to getting activated. They're missing some of the conserved motifs, some of the disulfide bridges. I think it has something to do with their architecture that makes it easier to activate them." "I often tell new PIs that the fact that I had to choose a topic with a specific flavor - that actually was good for me. Because that kind of made for me a niche which would be different from what my postdoc lab was doing." "It's such a small change and you get this effect. We know that the sweet taste receptor is involved - and how exactly, that is ongoing." "Let's not think about bitter as something just to get rid of, or try to put a lot of sugar on top of it so you don't feel it. Instead, try to get used to it - and accept that it's actually not bad." About this episode Dr. Niv is currently an associate professor and vice dean for research at the Hebrew University of Jerusalem. The Niv lab is also part of the Global Consortium for Chemosensory Research. Masha earned her Bachelor’s degree in chemistry, followed by a direct Ph.D. at the Institute of Chemistry, at The Hebrew University of Jerusalem in Israel. Dr. Niv trained as a postdoctoral fellow at Weill Cornell Medical College. Her work focuses on both sweet and bitter taste receptor GPCRs and her lab established the BitterDB . Dr. Masha Niv on the web Niv Lab LinkedIn Twitter Pubmed Google Scholar Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Nicola J. Smith About Dr. Nicola J. Smith Dr. Nicola J Smith is an expert in molecular pharmacology with a track record in exploring GPCR structure-function relationships in the context of cardiovascular disease and metabolic disorders. She is a National Heart Foundation of Australia Future Leader Fellow and runs a laboratory of 7 Ph.D. and Honours students at UNSW Sydney, where she has recently been promoted to Associate Professor. Most recently, Dr. Smith’s team has made advances in the understanding of how an orphan GPCR exerts its effects both in vitro (cell culture and ex vivo models) and in vivo (measures of physiological and pathological cardiometabolic function in unconscious and conscious mice). Together with Irina Kufareva , UCSD, her team developed a novel approach to identifying ligands for orphan GPCRs by developing a powerful new computational tool for identifying ‘surrogate’ ligands (borrowed from other receptors) for orphan GPCRs, named GPCR-CoINPocket. Her career goal is to leverage this expertise to establish a research program that takes orphan GPCRs from ‘locked’, inaccessible receptors to well-characterized and understood ‘unlocked’ therapeutic targets with high-affinity ligands. Dr. Nicola J. Smith on the web UNSW Sydney LinkedIn Retraction Watch Twitter Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Bruno Giros About Dr. Bruno Giros Dr. Giros' lab investigates how molecular changes at the nerve synapse might impact integrated behavior and what we might learn from these mechanisms to cure mental illness. After doctoral training at the Pierre and Marie Curie University in Paris and a short internship at Genentech Inc. in South San Francisco, he joined the CNRS as a Research Fellow in 1987 in the INSERM Laboratory directed by Jean-Charles Schwartz in Paris, where he cloned and characterized dopamine D2 and D3 receptor subtypes. From 91 to 94, he was an assistant professor at Duke University in North Carolina, working with Marc Caron and Robert Lefkowitz (2012 Nobel Prize in Chemistry) to characterize several neurotransmitter transporters and kinases and establish the first knock-out for these genes. In 1999, in France, Dr. Giros created the INSERM/CNRS laboratory on the "Neurobiology of Psychiatric Disorders," first in Créteil with Marion Leboyer, then at the University of Paris-Sorbonne with Hervé Chneiweiss. Since 2008, he has arrived at McGill University as a Canada Research Chair. At McGill, his laboratory has two main axes of research: 1) Studying interindividual vulnerability to chronic stress and depression and; 2) Understanding the role of phenotypically defined subpopulations of striatal neurons in motor and cognitive functions. Bruno Giros has trained 59 master's, doctoral and postdoc students, most of his trainees obtain positions in the academic or private sectors or are currently pursuing postdoctoral research training or have entered medical studies. Dr. Giros has published more than 200 publications with an H factor of 79 and 32,000 citations (Google Scholar) and has received several distinctions, including the CNRS silver medal, the FRM "Young Researcher" prize, the ISI “Highly Cited” and F-1000 in Pharmacology, and recently received the Heinz Lehmann Award from the Canadian College of NeuroPsychopharmacology and the distinguished James B. McGill Professor Award. Dr. Bruno Giros on the web Dougles Research Center LinkedIn Google Scholar Researchgate Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. Aaron Sato on building the synthetic antibody library that finally makes GPCRs tractable — and the greenfield strategy that led him there. << Back to podcast list Strategic Partner(s) Aaron Sato: Synthetic Antibody Libraries for the Hardest GPCR Targets GPCRs account for a substantial fraction of validated drug targets, yet most are drugged by small molecules — antibodies against GPCRs remain notoriously difficult to discover. This conversation explores how synthetic antibody phage display libraries, built on silicon-based DNA synthesis, are rewriting that constraint. Dr. Aaron Sato, CSO of Twist Biopharma, describes the motif-directed library his team developed by collecting known GPCR-binding sequences from protein, peptide, and antibody ligands and seeding them into the heavy chain CDR3 of a fully human synthetic library. The discussion covers why degenerate oligos had been the bottleneck for library quality, how a "library of libraries" strategy sidesteps the ten-billion-variant ceiling that caps any single phage library, and why the team can now move from a GPCR target to a bivalent IgG ready for functional assays in eight to ten weeks. For Aaron, this work is personal: he has built his career hunting greenfield targets where others had failed — and GPCRs were the greenfield he had been waiting for. About the Guest Dr. Aaron Sato is the Chief Scientific Officer and VP of Protein Engineering at Twist Biopharma, the biologics division of Twist Bioscience. He earned his PhD at MIT in the laboratory of Lawrence Stern, where he studied structure-function relationships of MHC class II proteins by X-ray crystallography. His career has traced the evolution of antibody engineering, with leadership roles at DIAX, Oncomed, Sutro Biopharma, and Lake Pharma before joining Twist. His current focus is building synthetic phage display libraries that drug targets the field has long treated as intractable — GPCRs chief among them. Scientific Themes of the Conversation Silicon-based DNA synthesis and the end of degenerate oligos in library design Motif-directed library design — encoding ligand-binding sequences into CDR3 architecture The library of libraries as an answer to the diversity ceiling of single phage libraries Greenfield target selection as a drug discovery strategy Family-level cross-reactivity as an advantage, not an obstacle, in GPCR antibody discovery Timelines, automation, and the industrialization of antibody workflows Key Insights from the Conversation Silicon DNA synthesis removes the degenerate oligo bottleneck. Traditional synthetic libraries rely on degenerate or trinucleotide mixtures to encode CDR diversity, which limits control over which variants actually appear. Twist's silicon platform produces pools of discrete, designed sequences — a shift in how synthetic libraries are composed. The motif-directed library encodes prior biological knowledge directly into CDR3. By curating protein, peptide, and antibody motifs known to bind GPCRs and inserting them at the top of the heavy chain CDR3, the library enters each panning campaign already biased toward the target class. The design decision is the library's main differentiator. A motif-directed library reaches targets its motifs weren't designed for. The same library has produced antibodies against orphan GPCRs and receptors without peptide ligands, because the surrounding CDR diversity provides enough variation to find binders outside the seeded motif content. Phage display's ~10¹⁰ variant ceiling can be broken by stacking libraries. Any single phage library is capped near ten billion variants. Running multiple libraries in parallel moves the effective diversity toward 10¹² — the idea Aaron calls his library of libraries. Eight to ten weeks from a GPCR target to a functional IgG is the platform's working tempo, not a best case. By skipping fragment-based screening and going directly to full bivalent IgG, the team hands functional biology teams a molecule that is ready for flow cytometry and receptor assays almost immediately. Aaron's strategy is deliberately greenfield. He looks for target classes where existing platforms have already failed — not because the biology is easier, but because new technology is rewarded most where the incumbents have stalled. GPCR family architecture is a discovery advantage. Receptors within a family share sequence and surface topography, so an antibody recovered against one member is often a legitimate starting point for discovery across the family. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction and sponsor acknowledgment 01:53 The conversation begins 02:29 From MIT crystallography to leading Twist Biopharma 04:21 Twist Bioscience, Twist Biopharma, and the silicon DNA platform 08:12 Using DNA for long-term data storage — a parallel vertical 09:17 Why antibodies to GPCRs have stayed so intractable 09:29 The motif-directed library — encoding receptor motifs into CDR3 12:34 Why one antibody can open up a whole receptor family 14:36 Eight to ten weeks from target to tested bivalent IgG 17:21 The library of libraries — scaling past 10 billion 18:42 Who partners with Twist Biopharma today 22:45 Beyond oncology — inflammation, metabolism, cardiovascular 24:55 Running a protein engineering team through a pandemic Selected Quotes "Synthetic antibody phage display libraries are actually best used for really difficult to drug targets." "I often love to look for my greenfield areas, where there's not a lot of competition because there's just really no technology that enables you to drug specific targets." "In phage display, you're oftentimes kind of capped out around 10 billion different antibodies per library. One way around that limited diversity is to actually have multiple libraries." "GPCR antibodies are just so intractable oftentimes." About this episode In this episode of the Dr. GPCR Podcast , I spoke to Dr. Aaron Sato from Twist Biopharma , a vertical within Twist Bioscience . Aaron is currently the Chief Scientific Officer and VP of Protein Engineering. He earned his Ph.D. at the Massachusetts Institute of Technology, where he studied MHC class II structure-function relationships. His path led him to work in an industry where he assumed various responsibilities and roles in the antibody space. Aaron has a proven track record as a biologics leader as he led teams to discover and develop novel first-in-class antibody therapeutics. Dr. Sato published over 30 peer-reviewed papers and contributed to 40 issued patents in the antibody space. During our time together, Aaron and I discussed how using Twist Bioscience’s proprietary technology to manufacture DNA at a scale, the team saw an opportunity to tackle the challenge of identifying novel functional antibodies targeting GPCRs by incorporating these natural binding partners into Twist’s antibody library design. We’d like to extend a special thanks to Twist Biopharma for sponsoring this episode of the Dr. GPCR podcast. Dr. Aaron Sato on the web LinkedIn Twitter Google Scholar Twist Bioscience Twist Biopharma Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Richard Premont About Dr. Richard Premont "Dr. Premont obtained his B.S. in Biology and Chemistry at the California Institute of Technology in 1985, and M.Ph . and Ph.D. in Biomedical Sciences (Pharmacology) at Mount Sinai School of Medicine (City University of New York) in 1990 and 1992, working with Ravi Iyengar on regulation/desensitization of the liver glucagon receptor and glucagon-stimulated adenylyl cyclase system. In 1992, he won a Helen Hay Whitney Foundation fellowship to support his post-doctoral work with Robert Lefkowitz and Marc Caron at Duke University. His initial project to identify and clone taste receptors was unsuccessful, but led to the identification of GRK5 and continued focus on GRKs (particularly GRKs 4,5,6) and arrestins as GPCR regulators and as mediators of distinct signaling pathways through partners including GIT1. In 1999, obtained an independent faculty position at Duke in Gastroenterology, where he remained until 2018 studying GPCRs and their signaling pathways in the liver and in liver disease. In 2018, he moved to Harrington Discovery Institute and Case Western Reserve University, where he studies GPCR regulation by S-nitrosylation. My research focus is on understanding how distinct cellular signaling pathways interact and are coordinated to produce integrated physiological responses, and how dysregulation of this coordination results in pathophysiology. For this, we have worked in three main areas: the regulation of G protein-coupled receptor signaling particularly by the G protein-coupled receptor kinase (GRK) – beta-arrestin system, the coordination of heterotrimeric G protein, small GTP-binding protein and protein kinase pathways by GIT/PIX scaffolding complexes during cellular signaling, and characterizing the role of protein S-nitrosylation as a signaling post-translational modification in mediating and regulating cellular signaling pathways, particularly in conjunction with better characterized signaling systems. In our work, we utilize methods including structural biology and proteomics, molecular biology and biochemical enzymology, primary and model cell culture, and transgenic, knockout, knock-in and conditional models of mouse physiology and behavior." Dr. Richard Premont on the web Google Scholar LinkedIn Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. John Streicher on how HSP90 flips direction between brain and spinal cord, why isoform-selective inhibitors may rescue oral delivery of opioid adjuncts, and how a student's side project on intermittent fasting erased morphine reward in mice. << Back to podcast list Strategic Partner(s) Dr. John Streicher: Reorganizing Opioid Signaling Beyond the Receptor The dominant strategy for improving opioid therapy has been to engineer new ligands at the receptor itself — biased agonists, partial agonists, multi-target molecules. Dr. John Streicher's laboratory at the University of Arizona works a different angle. His team treats opioid signaling as a problem of circuit organization: the same kinases and second messengers produce radically different outcomes depending on how they are scaffolded inside a cell, and the chaperones that do that scaffolding are themselves druggable. In this conversation, Dr. Streicher describes how heat shock protein 90 plays directly opposite roles in the brain and the spinal cord, why isoform-selective HSP90 inhibitors may finally solve the "brain always wins" problem of oral delivery, and how a graduate student's skeptically-received side project on intermittent fasting produced some of the strongest opioid-sparing data his lab has generated. He came to this field because a signaling cascade felt like a puzzle he could not stop thinking about, and the puzzle has only gotten more interesting. Listeners will get a concrete look at what it means to modulate opioid pharmacology downstream of the receptor — and why the safety margins the field has been chasing for decades might actually live there. About the Guest Dr. John Streicher is an assistant professor in the Department of Pharmacology at the University of Arizona. His lab combines cell and molecular biology with animal pharmacology to identify new signaling regulators of the mu, delta, and kappa opioid receptors. Current lines of work include isoform-selective HSP90 inhibition as a strategy for widening the opioid therapeutic index, signal organization downstream of opioid receptors, and the unexpected effects of intermittent fasting on morphine pharmacology. Dr. Streicher trained in signal transduction during his PhD on heart failure and p38 MAP kinase, and moved into opioid pharmacology as a postdoctoral fellow with Dr. Laura Bohn at Scripps Research Institute. Scientific Themes of the Conversation Opioid signaling specificity as a problem of circuit organization, not molecular identity HSP90 as a region-specific signaling scaffold — opposite roles in brain and spinal cord Isoform-selective chaperone inhibition as an alternative to receptor-level drug design The current state and replication troubles of biased agonism at the mu opioid receptor Downstream pharmacology as an underexplored route to safer opioid therapy Intermittent fasting as a metabolic modulator of opioid antinociception and reward Key Insights from the Conversation Specificity lives in circuit architecture, not in the kinase itself. ERK MAP kinase is Dr. Streicher's recurring example: the same molecule promotes opioid antinociception in one context, drives chronic pain in another, and functions as a mitogen in cancer. You cannot explain specificity by assuming each node does one thing. What differs is how scaffold proteins localize the kinase into distinct submolecular circuits. He teaches his students to think of kinases as components — a diode in a radio and a diode in a nuclear bomb can be identical — and the organization around them decides the outcome. HSP90 runs opposite programs in brain and spinal cord. In the brain, HSP90 promotes ERK activation downstream of the mu opioid receptor and is required for antinociception. In the spinal cord, the same chaperone acts as a brake on ERK activation. Block it spinally and the dorsal horn lights up with phospho-ERK in response to opioid, routing through RSK1/2 to stronger pain relief. Block it in the brain and antinociception collapses. This is not a quirk — it is the central clue the lab has built a therapeutic strategy around. The "brain always wins" problem is solved by isoform selectivity, not by dose. With a non-selective HSP90 inhibitor given systemically, the brain effect dominates and pain relief is lost. But the brain only uses HSP90α in this context, while the spinal cord recruits α, β, and GRP94. Collaboration with Dr. Brian Blagg at Notre Dame on β-and-GRP94-selective compounds has produced proof-of-concept IV data that reproduces the spinal-cord benefits — more potent morphine, reduced tolerance — without the brain blockade. The route from "intrathecal only" to "oral pill" runs through isoform selectivity. Biased agonism is in a harder place than the field often acknowledges. TRV-130 was denied FDA approval for lack of clear safety advantage. A phospho-null mu knock-in mouse from Stephan Schulz's group showed reduced tolerance but no respiratory-depression benefit. Attempts to replicate the arrestin-knockout phenotypes on clean mouse backgrounds have failed. Dr. Mary Canals' group has argued that some of the apparent bias benefits may actually reflect low intrinsic efficacy. Dr. Streicher calls himself an "informed outsider" on bias now, but his read is that the field needs deeper mechanism before the strategy can be rescued. A student's side project erased morphine reward. Graduate student David Duran wanted to test intermittent fasting in mice. Dr. Streicher was skeptical but gave the project room. The result: a six-hour feeding window for seven days increased morphine's antinociceptive efficacy in multiple pain models, strongly reduced tolerance and constipation, and completely blocked morphine reward in conditioned place preference. Receptor signaling assays showed efficacy shifts in the spinal cord and tolerance attenuation in the periaqueductal gray. The paper is published in Pain , and the translational path is unusually short — you don't need a ten-year IND process to test a feeding schedule in patients. Do not pursue something "completely novel" as a junior scientist. HSP90 in opioids was far enough off the beaten path that Dr. Streicher spent years fielding reviewer skepticism — no one has studied this, is this even real? His retrospective advice is to pick something novel but "still in the tent" — close enough to what the field recognizes that you earn credibility before trying to chase the real heresies. The lesson is not to play it safe; it is that unfamiliarity costs you credibility before your data can speak. Broad targets are not automatically undruggable. HSP90 is 2–3% of the protein content of every eukaryotic cell. A trained pharmacologist's first instinct is that the side effect burden would be crushing. But second-generation pan-HSP90 inhibitors have shown acceptable tolerability in oncology trials, Dr. Brian Blagg's KU-32 actually promotes neuronal survival in diabetic peripheral neuropathy and is now in Phase 1, and isoform selectivity narrows the footprint further. Dr. Streicher argues the field's default assumption — pick a low-expression, tissue-restricted target — is more habit than rule. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction 01:22 Meet Dr. John Streicher 01:49 From heart failure to opioids — a path through signaling 07:49 Why the mu receptor still anchors his lab 09:51 The specificity puzzle — why ERK does a million things 13:31 What happened to biased agonism — replications in trouble 19:08 What's missing, and why HSP90 flips in the spinal cord 28:44 The "brain always wins" problem and isoform selectivity 33:05 HSP90 as Pac-Man — co-chaperones and the AHA1 clue 38:52 Picking projects that are "novel but in the tent" 47:25 The student's side project that blocked morphine reward 59:52 Running a lab through the first months of COVID Selected Quotes "A diode in your radio at home and a diode in a nuclear bomb could be exactly the same component but do radically different things depending on how they're organized." "The brain always wins. And when the brain wins, the antinociception is blocked — which is not what you want." "I'm normally a pretty skeptical, hard-headed person. But the data is the data. And I'm going to follow it." "Pick something that is novel, but is sort of still in the tent." About this episode Our guest in this episode of the Dr.GPCR podcast is Dr. John Streicher from the department of pharmacology at the University of Arizona. John started grad school in 1999 and spent some time figuring out what he was interested in. It turns out that it was signal transduction, and he worked on the signaling cascades involved in heart failure. His encounter and interest in signaling in the context of GPCRs during his postdoctoral training in Dr. Laura Bohn’s lab at Scripps Research Institute in Florida. Today, John and his team focus on understanding how signal transduction cascades downstream of the opioid receptors work, including the unique organization of chaperone protein Hsp90 modulation of opioid signaling in the brain versus the spinal cord. Dr. John Streicher on the web University of Arizona Department of Pharmacology Google Scholar Pubmed LinkedIn Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Discover Media Partner Packages with Dr. GPCR Ecosystem. Amplify your brand, reach a targeted scientific audience, and showcase your organization in the GPCR community. The Yearly Glow Only 12 companies per year are invited to become Yearly Glow partners. This isn't advertising — it's a strategic partnership that puts your brand at the center of the scientific conversations that matter most. 1,400+ GPCR scientists reached 25–50% Newsletter open rate 12 strategic partnerships per year — because quality matters Partner with us Today! Who Media Partnerships Are For? Companies that think in years, not quarters Strategic Media Partnerships are ideal for GPCR-focused companies that want to: Strengthen brand credibility and recognition within the GPCR research community Associate their brand with high-quality science, experts, and long-term ecosystem initiatives Be consistently visible across trusted educational and content platforms Build awareness and trust over time — not chase immediate leads If your primary goal is to drive inbound inquiries or make your services discoverable at the point of need, the GPCR CRO Bank may be a better fit. "Dr. GPCR is the world's largest nonprofit community focused on GPCRs. As a strtegic partner, you'll gain trusted access to an engaged audience of academic researchers, biotech teams, and drug discovery innovators — without having to fight for attention." Why Partner with Dr. GPCR? Featured across our nonprofit platform, trusted by thousands As a media partner, you'll be featured across our nonprofit platform, trusted by thousands of GPCR scientists and biotech professionals. Reach Qualified Researchers Connect with scientists who are actively looking for tools like yours, without the noise of general platforms. Build Trust Develop content that speaks their language and establishes your credibility in the GPCR research community. Join a Curated Ecosystem Become part of a collaborative, curated ecosystem — not just another name on a crowded vendor list. What You Get as Media Partner? Active visibility, not passive placement These touch points are designed to reinforce brand presence and credibility through repeated, trusted exposure — not direct lead generation. Yearly Glow Exclusive Gated Content Premium content assets created in partnership — gated to capture and nurture scientist engagement while contributing genuine value to the community. Strategy Partnership Ongoing strategic collaboration to align visibility initiatives with your goals and the community's needs. Launch Campaigns Strategic campaigns that actively drive scientist awareness and traffic toward your offerings, timed to maximize community attention. Logo Positioning Strategic Partner logos are featured across multiple high-traffic ecosystem pages, creating repeated visual association with trusted GPCR content and resources. Base Package — Included 🎙️ Featured Podcast Episode ✓ Be the guest on a dedicated episode of the Dr. GPCR Podcast ✓ Feature up to 3 team members to share your story ✓ Distributed across podcast platforms and social media ✨ Logo positioning ✓ Strategic Partner logos are featured across multiple high-traffic ecosystem pages, creating repeated visual association with trusted GPCR content and resources. 📣 Social Media Promotion ✓ Engaging posts about your organization ✓ Targeted to GPCR researchers and biotech professionals ✓ Shared on LinkedIn and X (Twitter) 📝 Blog Contributions ✓ Contribute to blog posts on the Dr. GPCR platform as a valued partner ✓ Share insights on product launches, scientific discoveries, or customer stories ✓ Reach a targeted scientific audience with your contributions. 📄 Custom Company Page ✓ Permanent company profile on the Dr. GPCR Ecosystem ✓ Logo, branding, and description of your mission ✓ Contact links and key highlights 📬 Newsletter Visibility ✓ Featured in our highly read weekly newsletter ✓ Tell your story with context, clarity, and purpose ✓ Bonus: Mentioned in podcast intros/outros 👩🔬 Premium Licenses ✓ 10 Scientists Premium Accounts ✓ 3 Non-Scientists Premium Accounts 🎤 Co-Branded Events & Training ✓ Collaborate on webinars and virtual training sessions to showcase your expertise ✓ Host educational events that focus on GPCR research ✓ Engage directly with the GPCR research community through these initiatives 12 per year — a commitment to quality Only 12 Yearly Glow seats are available each year to keep our ecosystem curated, impactful, and community-focused. Every partner deserves dedicated attention, personalized strategy, and genuine integration. This is real selectivity — a reflection of how seriously we take partner quality and community trust. Previous Partners Join these leading organizations Join these leading organizations in the GPCR research ecosystem. Book Book a 30-minute Strategy Call with Yamina Ready to Connect with the GPCR Community? With only 10 spots remaining for 2026... Secure your place in our exclusive media partner program today.

<< Back to podcast list Strategic Partner(s) Yao Lu (Jackie) About Yao Lu (Jackie) "Jackie is a Ph.D. student, at Monash University, Australia, investigating the role of functional selectivity in a novel class of potential antipsychotics for the treatment of schizophrenia. Her work involves the pharmacological and structural characterisation of novel putative antipsychotic small molecules. Her research aims to provide a molecular explanation of small molecules for their pre-clinical efficacy and to support the design of novel therapeutics. " Yao Lu (Jackie) on the web Monash University Georgina Sweet Fellowship Authorea Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Lukas Grätz About Dr. Lukas Grätz "After a BSc in biology and a MSc in bioinformatics, I have been working in David Gloriam's group as a bioinformatician. My initial focus was on creating an automated chimeric homology modeling pipeline for GPCRs and since have branched out to multiple areas of GPCR research such as sequence alignments, generic numbering systems, structure data, G protein and arrestin coupling and more. As a developer, and more recently the lead developer of GPCRdb my day-to-day work centers around the maintenance and resource/tool development of GPCRdb and its sister databases. I am also affiliated with György Keserű's group at the RCNS in Hungary. I lived in Denmark, Poland, now I live in Hungary. I am married, I have two daughters. In my free time I like to play the guitar, sing and play board games. " Dr. Lukas Grätz on the web Karolinska Institutet ResearchGate PubMed Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Oliver Hartley About Dr. Oliver Hartley Oliver Hartley is VP for Drug Discovery at Orion Biotechnology . He is the inventor of OB-002 as well as the key technology underlying Orion’s discovery platform. Trained as a biochemist, he completed a PhD in protein engineering (Cambridge, UK) with Sir Gregory Winter (Nobel Prize for Chemistry, 2018). Since then Oliver has worked at the University of Geneva, where his research on peptide engineering and GPCR pharmacology has led to a series of high-profile publications and new intellectual property, and at the Mintaka Foundation for Medical Research with a role as co-founder and Chief Scientific Officer. Dr. Oliver Hartley on the web LinkedIn Orion Biotechnology Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Nobel laureate Robert Lefkowitz traces the accidental origins of his receptor research — from a Vietnam War draft to the cloning of the beta-2 adrenergic receptor — and reflects on what it takes to choose the right scientific problem and survive 50 years of failure. << Back to podcast list Strategic Partner(s) Robert J. Lefkowitz: Beta-Adrenergic Receptors, the GPCR Family, and Fifty Years of Discovery The existence of hormone receptors as discrete molecular entities was, for much of the 20th century, an open question. When Robert Lefkowitz arrived at the NIH in 1968 — not by scientific calling but by a Vietnam War draft assignment — the prevailing view held that receptors were at best allosteric binding sites on adenylyl cyclase. There was no proof they were physically distinct molecules. Over the following decades, Lefkowitz and his collaborators transformed this conceptual uncertainty into molecular fact. Using radioligand binding assays developed for the beta-adrenergic receptor system, his lab purified, then cloned the beta-2 adrenergic receptor — a 1986 Nature paper that unexpectedly revealed structural homology with rhodopsin and established the GPCR superfamily. The same system yielded the discovery of beta-adrenergic receptor kinase (now GRK2) and the beta-arrestins — three of the four central molecular components of GPCR signaling. This conversation traces the scientific logic and human contingency behind those discoveries: how to choose a problem at the edge of tractability, what failure looks like at 98%, and why Lefkowitz considers sharing a Nobel Prize with his own trainee the most personally meaningful moment of a fifty-year career. ABOUT THE GUEST Dr. Robert J. Lefkowitz is James B. Duke Distinguished Professor of Medicine and Biochemistry at Duke University, where he has led his laboratory since 1973. His research established the beta-2 adrenergic receptor as the primary model system for understanding GPCR structure, regulation, and signaling — work that produced the first purification, cloning, and sequencing of a GPCR and led directly to the recognition of the receptor superfamily. His lab developed the GRK (G protein-coupled receptor kinase) family and discovered the beta-arrestins, proteins now understood as central mediators of receptor desensitization and G protein-independent signaling. In 2012, Dr. Lefkowitz was awarded the Nobel Prize in Chemistry, shared with Brian Kobilka, for studies of G protein-coupled receptors. SCIENTIFIC THEMES OF THE CONVERSATION The receptor hypothesis before proof — The conceptual and experimental gap between classical pharmacology's functional receptor concept and the physical demonstration that receptors are discrete molecular entities. Beta-adrenergic receptors as a model system — Why the adrenergic system, with its rich pharmacological toolkit and cardiovascular relevance, made it the right platform for receptor biochemistry. Radioligand binding and the first demonstration of GPCR structure — The methodological progression from iodinated hormone binding to radioligand development to purification, and what each step required. The cloning race and the serendipity of the intronless gene — Competing against Genentech's molecular biology infrastructure, screening a genomic library against expert advice, and the unexpected absence of introns that closed the race. High output vs. low output failure: choosing the right scientific problem — The framework Lefkowitz articulates for navigating between trivial, solvable problems and important, intractable ones — and how that judgment is transmitted through mentorship. Scientific lineages and the transmission of scientific taste — How the values that make a scientist effective — problem selection, tolerance for failure, the instinct to pursue surprising results — are absorbed through proximity rather than instruction. KEY INSIGHTS FROM THE CONVERSATION 1. Receptors were an unproven concept when Lefkowitz chose to study them When Dr. Lefkowitz committed to receptor research in the early 1970s, prominent pharmacologists, including Raymond Ahlquist — who had introduced the alpha/beta receptor classification — publicly disputed the physical existence of receptors. At a 1973 symposium, Ahlquist responded to Lefkowitz's research plans by stating in print that hormone receptors were "a figment of Dr. Lefkowitz's imagination." Choosing that problem required betting a career on a concept that the field's own architects considered speculative. 2. The strategic logic behind choosing beta-adrenergic receptors The selection of the beta-adrenergic system was not intuitive — it was architectural. Dr. Lefkowitz identified three requirements: a receptor linked to adenylyl cyclase (providing a proximate, measurable downstream signal), cardiovascular relevance (matching his clinical training), and a pharmacological toolkit deep enough to support radioligand synthesis, analog competition studies, and affinity chromatography. The adrenergic system was the only one that satisfied all three. He reflects, fifty years later, that it was probably the smartest research decision he ever made. 3. The cloning race was won by doing the thing experts said was stupid Competing against Genentech — then the world leader in recombinant DNA technology — Dr. Lefkowitz's lab was getting nowhere screening plasmid libraries. When Brian Kobilka proposed screening a genomic library, Merck's molecular biology collaborators called it a stupid idea: introns would make a genomic clone useless. Lefkowitz and Kobilka screened it anyway. Not only did they pull clean clones immediately — they found that the beta-2 adrenergic receptor gene contains no introns, only the third mammalian gene to that point discovered to be intronless. The race ended. 4. The moment the GPCR family became visible As sequencing of the cloned beta-2 AR proceeded in 1985–86, Lefkowitz expected the receptor to look like nothing else — the first member of an unknown family. The discovery that it was structurally homologous to rhodopsin was a complete surprise. Functional analogies between the two systems had been recognized — both were G protein-coupled — but no one had predicted structural relatedness. The realization that the sequence matched a known protein was, as Dr. Lefkowitz describes it, "a total shocker." It was the moment they understood that all GPCRs would share this architecture. 5. The 98% rule and what it means to take on important problems Dr. Lefkowitz describes a senior scientist at the NIH who told him early in his career that the difference between an average scientist and a world-class one is the failure rate: 1% success versus 2%. He has carried that framing for fifty years. When a collaborator once told him that nearly everything he was working on was succeeding, Lefkowitz told him that was a problem — if 50% of your experiments work, you are not working on hard enough problems. He aims for 10–20%. 6. Mentorship is absorbed, not taught Dr. Lefkowitz argues that the most critical skill in science — choosing a problem that is important but tractable — cannot be explained by a mentor. It is acquired by watching: how a scientist moves between problems, when they persist, when they drop something, what surprises them enough to redirect attention. This is why scientific lineages exist. The values that produce important work are transmitted the way values always are — through proximity, observation, and time. 7. Sharing the Nobel with a trainee he never interviewed When Dr. Lefkowitz learned at 5 AM on October 10, 2012, that he had won the Nobel Prize in Chemistry, his first reaction was not elation — it was relief. The question he had been asked for years — when are you going to win the Nobel Prize? — would never need to be asked again. His second reaction, on learning he would share the prize with Brian Kobilka, was more personal. Kobilka had applied to Duke without ever meeting him, had joined the lab without an interview, and had been the scientist at the bench for the cloning work that anchored the prize. "That brought a tear to my eye." EPISODE TIMELINE Timestamps are AI-generated from the transcript and are approximate. Exact times may vary slightly from the published recording. 00:00 Introduction 01:29 How Dr. Lefkowitz became a scientist — a story of pure accident 08:12 The Vietnam War draft, the NIH, and the two-year assignment that redirected a career 14:02 The Yellow Berets: one 100-person cohort and ten future Nobel laureates 22:30 Choosing the beta-adrenergic receptor system — the strategic logic behind fifty years of work 39:30 High output vs. low output failure: navigating between the trivial and the intractable 46:32 Mentorship as osmosis — what you absorb from watching a scientist think 53:42 Cloning the beta-2 adrenergic receptor and the unexpected homology with rhodopsin 01:05:33 The intronless gene: how a "stupid idea" ended the race against Genentech 01:08:09 On failure: why 20% success means you are not taking on hard enough problems 01:15:17 The Nobel call at 5 AM: quiet relief, a pot of coffee, and one phone call to Brian 01:35:54 Work-life balance: an honest answer SELECTED QUOTES "It was that serendipitous event of the Vietnam War and going to the NIH — not because I was dying to do research, but just because I didn't want to be dying in Vietnam. It was that serendipitous event that basically changed the entire course of my life and career." "He got up and said, it's all very nice. But he says, this is a figment of Dr. Lefkowitz's imagination. There's no such thing as a receptor. And I remember thinking to myself as a young buck at the time: I'm going to show this guy. It took a hell of a long time." "If half of everything I'm trying to do is working, I'm not taking on very challenging stuff. I really stick around 10 or 20%. What you're seeing is a trivial fraction. Most of what we do fails. But that's science." "It was more a sense of relief, I think, and quiet satisfaction. The monkey's off my back. I realized in that moment that I would never again have to answer the question: Bob, when are you going to win the Nobel Prize?" About this episode It was December 14th, 2020, 1:50 pm, when I turned on my laptop and signed into Zoom for my chat with Bob. Bob, who, you might ask? Well, it’s the one and only Robert J. Lefkowitz, M.D., 2012 Nobel Prize in Chemistry, which he shared with Dr. Brian Kobilka . Bob doesn’t really need an introduction since his reputation precedes him. Before we pressed record, I asked if I could call him Bob, and he answered that only his mom used to call him Robert, especially when she was upset with him. I then pressed record, and we chatted for almost 2h about Bob’s career, discoveries, difficulties (yes, he’s had some too), Nobel week, and his memoir that he just published in collaboration with Dr. Randy Hall. Bob is James B. Duke Professor of Medicine and Professor of Biochemistry, Chemistry, and Pathology at the Duke University Medical Center. He began his career in the late 1960s and has been an Investigator of the Howard Hughes Medical Institute since 1976. His legacy lies in the numerous discoveries he and his team made in the GPCR field and in all those who trained in his laboratory and went on to pursue stellar scientific careers. I very much enjoyed chatting with Bob, and I hope you’ll enjoy learning more about him as well. Dr. Robert J. Lefkowitz on the web A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist Duke University Wikipedia Nobel Prize HHMI Lefkowitz Lab Google Scholar Pubmed Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

xperience everything inside Dr. GPCR University for 14 days. Live Masterclasses, 200+ recordings, the GPCR Intelligence Hub, job listings, and a 1,400+ scientist community. $49 — credited toward your first year if you stay. 🎓 Dr. GPCR University See what it feels like to have a professional home in GPCR science 14 days. Full access. Everything inside University — Masterclasses, intelligence, jobs, community. And if you stay, your trial fee comes back as a credit. $49 14-days of full Premium access Credited toward your first year Start Your 14 Days Your $49 becomes a credit toward the $499/year membership. You pay $450 if you stay. 1,400+ Scientists in the community 200+ Recordings $0 Net risk if you convert The Hook The Masterclass alone is worth the trial Live sessions with leading GPCR scientists. Ask your question. Be in the room. This is the single experience that makes people realize what University is worth — and it's yours from day one of the trial. What's Inside Everything University members have. Nothing held back. For 14 days, you're not testing — you're experiencing what it's like to have a professional home in GPCR science. Live Masterclasses Monthly sessions with leading GPCR scientists. Ask questions, hear perspectives, be part of the scientific conversation — live. Premium Weekly News Curated GPCR intelligence with job listings, events calendar, and classified industry news that free members don't see. 200+ On-Demand Recordings Every past Masterclass, searchable and organized. Filter by category, level, or instructor and learn at your pace. Community & Forum Ask the Ecosystem. Connect with peers. Access the full member network of 1,400+ GPCR scientists worldwide. GPCR Intelligence Hub The most comprehensive searchable GPCR resource archive in the field. Every resource, every tool — filterable and at your fingertips. Job Listings & Events GPCR-specific positions and upcoming events curated for the community. See what's opening in your field — before everyone else. The Math Your trial fee is never lost The $49 comes back as a credit. Either way, you win. Your $49 becomes a coupon. The trial fee becomes an investment, not an expense. You Already Belong The trial opens the rest of the house If you're reading the Weekly News, listening to the podcast, or you attended a Happy Hour — you're already part of this community. Walk in. Weekly News reader - Podcast listener - Happy Hour attendee 🔥 Upgrade to Premium 14-Day Full Access Trial $49 $ 49 Get 14 days of full access to Dr. GPCR University for $49. Explore expert-led masterclasses, curated intel, and a scientific community shaping GPCR drug discovery. Valid for 14 days Join Premium Today! On-demand masterclass library Weekly curated intelligence briefings with expert analysis Community access — connect with scientists and biotech leade Full resource library and member tools Priority invitations to live expert Q&A sessions "The conversation you have inside a Masterclass — that alone changes how you think about your work. University is where GPCR scientists come to stay sharp." — Jay, Dr. GPCR University Member The Comparison A society membership costs more and gives you less Here's what $450 (net after trial credit) gives you inside Dr. GPCR University compared to a typical scientific society. Questions Before you walk in What do I get during the 14 days? Full Premium access to everything inside University — live Masterclass sessions, 200+ on-demand recordings, the GPCR Intelligence Hub, Premium Weekly News with job listings and events, Ask the Ecosystem forum, and the full member network. Nothing is restricted. What happens to my $49 if I become a member? It becomes a credit. You receive a $49 coupon toward the $499/year membership, so your net cost for the first year is $450. Your trial fee is never lost. Is this a free trial? No — and that's by design. The $49 means you're serious, and we're serious about giving you the full experience. Nothing is held back. You get everything Premium members have for 14 days. Can I start anytime? Yes. Your 14 days begin when you start. The trial is not tied to a specific Masterclass date — though starting near a live session means you'll get the highest-impact experience. What happens when the 14 days end? You'll receive a $49 coupon toward the $499/year membership. If you stay, you pay $450 for your first year. If you don't, you've spent 14 days with full access to the most comprehensive GPCR ecosystem in the field. Either way, you win. How does this compare to a society membership? Most GPCR-relevant society memberships cost $200–$600+ per year and offer a fraction of what University includes. Monthly live Masterclasses, a searchable intelligence archive, curated job listings, a weekly premium news digest, and a focused community — all for $450 net after trial credit. Come in. See if it's home. 14 days. Full access. $49. And if you stay, it comes back as a credit toward your first year. Start Your 14 Days $49 credited toward $499/year membership · Net cost $450 if you stay

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Browse past events hosted by the Dr. GPCR Ecosystem, featuring scientific meetings, workshops, and collaborations that brought the GPCR community together. Past Events - Where the Dr. GPCR community comes alive Welcome to the page where the heart of the Dr. GPCR community comes alive! Here, we celebrate the incredible moments that brought scientists, researchers, and GPCR enthusiasts together to share groundbreaking discoveries, spark new ideas, and forge lasting connections. From immersive workshops and high-energy summits to intimate retreats and virtual conferences, each event represents a milestone in our shared mission to advance GPCR science and collaboration worldwide. 👉 Dive into our event archive below to relive the energy, inspiration, and community spirit that make Dr. GPCR truly special. Be part of our journey — stay inspired by our collective passion for science, learning, and discovery. Adhesion GPCR Workshop 2024 Endocrine Metabolic GPCRs Meet Inoviem Team GPCR ECI Transatlantic 2022 Editorial: GPCR and G Protein-Mediated Signalling Events in the Nervous System Dr. GPCR Ecosystem 2.0: Collaborating better Dr. GPCR: Advancing GPCR Drug Discovery Through Collaboration Discovery On Target 2024 GPCR targeted drug discovery Summit 2024 GPCR targeted drug discovery Summit 2023 The Dr. GPCR Podcast GPCR targeted drug discovery Summit 2022 Dr. GPCR: Where all GPCRs are created equal Dr. GPCR: Beyond the lab GRS and GRC Switzerland GPCR Retreat 2023 Leadership is a learned skill - PhageMed Unige GPCR Retreat 2022 Dr. GPCR: Beyond the lab Dr. GPCR: From idea to Ecosystem Dr. GPCR: Beyond the lab