Explore the world of GPCRs with Dr. GPCR Podcast! Join industry leaders as they share insights, stories, and groundbreaking discoveries, enriching our understanding of GPCRs. Delve into the science behind these vital components shaping our collective knowledge. Welcome to the Dr. GPCR Podcast - The Voice of the Community Conversations with the world’s leading GPCR scientists. Exploring discoveries, careers, and ideas shaping human health. In each episode, we sit down with leading experts to explore their career journeys, groundbreaking discoveries, and the impact of their research on our shared understanding of GPCR biology. Launched at the height of the pandemic, the Dr. GPCR Podcast was created with three goals: Share discoveries – Highlight the latest advances in the GPCR field. Amplify voices – Provide scientists a platform to showcase their work. Inspire the future – Motivate the next generation to pursue GPCR research. At its core, Dr. GPCR’s mission is simple yet ambitious: to bring the GPCR community together - across borders and disciplines - to connect, exchange, and collaborate in order to improve human health through a deeper understanding of GPCR biology. Latest Podcast Episodes More podcast episodes Dr. GPCR Podcast Audience Survey We are currently planning our next season and need your help. This short survey will help us understand your needs to bring you exciting and informative content. We also know that you are busy, which is why we designed this short survey that should take you 5 minutes. Fill out this form Be our Guest In each episode, we chat with an expert about their career trajectory, discoveries, and how their research contributed to the shared pool of knowledge about GPCR biology. We’d love to have you on our podcast. To be a guest, fill out the form below, and we’ll be in touch in 48 hours. Fill out this form What others are saying about this podcast "You made it a very comfortable and engaging experience, and it felt like we were chatting over coffee — Yamina thoughtfully guided our chat throughout." Anita Nivedha I think it's really well done. I'm genuinely interested to see how it evolves and grows over time, as I feel it has the potential to develop into something even more impactful. Anonymous This came at just the most perfect time. I hadn't heard a scientific talk outside my lab since February and was starved to hear someone else talk passionately about GPCRs. I've listened to the episodes multiple times and it's just like being at a conference getting new ideas. I just couldn't be happier y'all created this podcast. Anonymous Great initiative, thanks. Carrier paths, choosing research topics, switching fields, late start, failures and successes. Anonymous I enjoy the breadth of questioning that goes beyond just the science, and reveals a bit about the scientists as individuals/mentors/people. Anonymous Really enjoyable science podcast! Dr. Yamina Berchiche interviews leading GPCR scientists on this vibrant, entertaining podcast. I really appreciate the way the podcast educates and mentors, particularly towards junior scientists but also to the community as a wholen Yamina is a great interviewer, getting insight and personal history from her guests. Am very grateful for Dr GPCR livening up the week in these difficult times! Sam @Pharmamechanic Listen and subscribe where you get your podcasts

Advanced GPCR webinars for pharmacologists and biotech scientists. Live Q&A. Deep mechanistic insight. Reserve your seat. University / Free & Live Webinar Live GPCR Webinars with the World's Leading Experts. Deep-dive sessions focused on real pharmacology, real drug discovery challenges, and real translational insight. Live Q&A with the scientists shaping the field. Live for those who can be there. On demand for everyone else. 👉 Sign Up for Notifications Get the live link before each session Strategic Partners Webinars Upcoming Live & On Demand Webinars Tuning GPCR System Sensitivity: Revealing True Drug Activity Through Functional Volume Control Speaker: Dr. Terry Kenakin | Terry's Pharmacology Corner What you'll learn during the session: How functional system sensitivity for receptor expression becomes a tool for determining the properties of a molecule Why testing agonists in low sensitivity systems separates affinity and efficacy and enables prediction of agonism in other systems How testing antagonists in high sensitivity systems detects low levels of efficacy and, through constitutive activity, inverse agonism How volume control reveals essential properties of allosteric modulators, including PAM-agonism and changes in efficacy 📅 September 24, 2026 at 11:00:00 AM Details Recombinant Antibodies for GPCRs: A Challenge to the Community Speakers Dr. Alexander Ball, MD Dr. Alexander Ball of GeneTex joins Dr. GPCR to walk through what the company is doing about it, and the challenge it comes with: A high-throughput recombinant antibody platform built for specificity at scale Prioritized validation: CRISPR KO/KD, endogenous expression, cell fractionation, comparable antibodies, application-specific testing VirDTM-GPCR arrays for cross-reactivity screening when feasible More than 300 recombinant mAbs against almost 200 human GPCRs, and growing Free samples for GPCR researchers who will test the antibodies in their own labs and give structured feedback 📅 June 25, 2026 at 11:00:00 AM Details Receptor Signaling Bias: A Valuable and Accessible Property of New Drug Candidates Speaker Dr. Terry Kenakin - UNC Chappel Hill | Terry's Pharmacology Corner Topics Covered The biological basis of receptor signaling bias and ligand-dependent conformations How to design functional assay panels that quantify bias rather than infer it Interpretation pitfalls and what assay system choice does to bias estimates Translating pathway-level data into lead selection and optimization decisions Why potency alone is not enough for candidate-level decisions 📅 May 28, 2026 at 11:00:00 AM Details 1 2 1 ... 1 2 ... 2 1,400+ Scientists in the Ecosystem 30+ Countries Represented 60–90 Scientists per Live Session Free Always. No Paywall. No Catch. Use It Tomorrow Practical takeaways, every session. Walk away with something you can apply in your next experiment, assay, or project decision. Together in the Room Scientists from around the world, in the same conversation. The chat, the Q&A, the shared curiosity — the community thinking together in real time. Free and Generous No paywall. No catch. The ecosystem gives this away because GPCR scientists deserve access to high-quality science. Sign up, show up, bring your questions. Direct Access Ask an expert a live question and get a real answer. That direct access doesn't exist at conferences — it exists here. No Borders Live for those who can be there. On demand for everyone else. The GPCR community doesn't stop at borders — and neither do we. Stay Ahead Learn about methods, tools, and approaches before they become widely known. Be ahead of colleagues who aren't in the ecosystem. What Makes These Webinars Different? Not a lecture. A scientific exchange. Built for the GPCR community, by the GPCR community. Every session is designed to move your science forward. First Dr. GPCR event? Welcome. This is what the community looks like — scientists from around the world, thinking through discovery challenges together. There's no paywall, no catch. Just real science and real exchange. If this is your first session, there's a lot more where this came from. Want to Go Deeper? This Is Just the Beginning If a free webinar is this good, imagine what the full ecosystem looks like. Dr. GPCR University brings you premium Masterclass sessions, 200+ recordings, weekly curated news, and a global community of GPCR scientists — all in one place. Webinar → Weekly News → 14-Day Trial → University Premium 👉 Sign Up for Notifications These sessions are part of a larger mission: building the most trusted home for GPCR scientists worldwide. Frequently Asked Questions Questions about the webinars What are GPCR webinars? GPCR webinars are free, live online scientific sessions focused on G protein-coupled receptor biology, pharmacology, signaling, and drug discovery. Each session explores mechanistic models, translational challenges, and real-world therapeutic implications through presentations and live Q&A. They're designed for scientists who want deep, data-driven discussion rather than surface-level overviews. Who should attend? Any scientist working with GPCRs — pharmacologists, medicinal chemists, cell biologists, translational researchers, discovery teams, postdocs, PIs, and industry scientists. Whether you're deep in receptor biology or evaluating assay tools, these sessions are built for you. Are the webinars free? Yes. Always. No paywall, no catch. Sign up with a free registration and you'll receive the live link before each session. Recordings are also freely available on demand afterward. Are the webinars live or pre-recorded? All webinars are live events with real-time Q&A — that's the point. After the live session, the full recording becomes available on demand so scientists in every time zone can access the same content and depth. How are these different from conference talks or academic seminars? The Q&A is the core, not an afterthought. These sessions are designed for interaction — scientists asking direct questions and getting real answers. There's no travel required, no registration fee, and you're in a room with researchers from dozens of countries who share your focus on GPCRs. What topics are typically covered? GPCR pharmacology, signaling, structural biology, allosteric modulation, biased agonism, assay design, drug discovery workflows, translational challenges, and the science behind emerging tools and methods. Every session is grounded in receptor biology with a focus on what's practical and applicable. Do I need prior knowledge of GPCR pharmacology? A working understanding of GPCR biology helps you get the most from each session. That said, the presenters are skilled at making complex science accessible, and the Q&A often covers foundational questions alongside advanced discussion. Where can I find more advanced GPCR training? If you want to go deeper, Dr. GPCR University offers premium Masterclass sessions with frontier science, unresolved questions, and extended scientific exchange — exclusively with independent scientists. The webinars are the open door; Masterclass is the room you earn access to. You can explore University with a 14-day trial. Be in the Room When the Science Moves Forward Sign up to get notifications about upcoming webinars. Bring your questions. 👉 Sign Up for Notifications

Dr. GPCR Podcast - The Voice of the Community Whether you’re a scientist, student, or just curious, you’ll hear about discoveries, career stories, and the latest GPCR news. Jump in and get inspired! Strategic Partners Latest Podcast Episodes Select by Guest Name 2026-09-09 2026-05-13 2026-03-18 2026-02-04 2026-06-10 2026-04-29 2026-03-04 2025-12-17 2026-05-27 2026-04-01 2026-02-18 2025-12-03 1 2 3 4 5 1 ... 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 ... 16 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 Listen and subscribe where you get your podcasts

Join the scientific exchange in the room with the scientist, not watching from the audience. Access 200+ expert sessions at Dr. GPCR University. University / Live Masterclass Sessions In the room with the scientist, not watching from the audience. Live scientific exchanges with leading GPCR experts. Interactive, question-driven, frontier science. This isn't a lecture — it's a conversation with the people shaping GPCR discovery. Masterclass is included inDr. GPCR University Try it for 14 days Upcoming live sessions Your next Live Masterclass Session is waiting Each session focuses on a specific pharmacology or GPCR discovery topic, led by a recognized expert. Live Q&A means your questions get real answers. Introduction to GLP-1 pharmacology Dr. Marsha Pierce | Midewestern University October 29, 2026 Translational Pharmacology & Disease Models Details Conformational Biosensors for GPCR Activation Dr. Katarina Nemec and Dr. Romy Thomas December 10, 2026 Assay Development Details What makes this different? Not a lecture. Not a webinar. A scientific exchange. The Masterclass was created because the most valuable insights in GPCR science aren't captured in papers or conference talks. Scientist-to-scientist discussion Extended Q&A allows deeper exploration than typical presentations. You're engaging directly with the expert — not submitting a question to a moderator. Beyond conference time limits Topics are explored in greater depth than standard conference talks allow. Sessions focus on scientific reasoning, data interpretation, and real discovery problems. Focused audience of specialists Sessions bring together GPCR researchers, pharmacologists, and discovery scientists. The conversation stays at the right level because everyone in the room speaks the same scientific language. Every session recorded Can't make it live? Every Masterclass is recorded and available on demand in the library. Revisit the science anytime — over 200 sessions and growing. On-demand library 200+ expert sessions, available anytime Full recordings of every Masterclass session. Revisit the science at your pace — filter by category, level, or instructor. Explore all Recorded Masterclasses → The scientists Learn directly from world leaders in GPCR research Adriano Marchese Dmitry Veprintsev Marsha Pierce Sudarshan Rajagopal Andrew Tobin Jakob Höppner Matteo Pavan Terry Hébert Bryan Roth Katarina Nemec Romy Thomas Terry Kenakin Davide Calebiro Kenneth Jacobson Samuel Hoare Yamina Berchiche What scientists say? From the people in the room I am a convert! I will keep Dr. GPCR and the offered resources in my work sphere Dr. Hoare is very experienced in the field. What came as a pleasant surprise was how didactical and well-thought-out his course was—highly recommended. The really unexpected was that the Q&A sessions reached the highest level—beyond excellent. GPCR researcher Thank you for bringing this course with Dr. Kenakin. I wish Dr. GPCR the best for the sake of promoting more educational opportunities that are sorely needed in the field GPCR researcher The content had enough depth to satisfy the hunger for theory while being full of practical knowledge GPCR researcher The best pharmacology teacher teaming up with the best GPCR community platform to help train and inspire the next generation of scientists. Also super-valuable for those of us learning how to teach pharmacology GPCR researcher Dr. Hoare's extensive and elaborative explanation of the topics at hand was excellent and very digestible. Thoroughly enjoyed learning from him GPCR researcher Dr. Kenakin is a leading expert in the field. Aside from his vast experience in drug development, not to mention his extensive publication record, Dr. Kenakin is a masterful teacher and communicator. GPCR researcher The course was very practical and easily translatable to experiments that we could do in our own labs. It was clear that Dr. Hoare is very in touch with the technical and human challenges we encounter in our work GPCR researcher About the GPCR Masterclass What is a GPCR Masterclass? The GPCR Masterclass is a live scientific discussion with a leading expert in GPCR pharmacology, receptor biology, or drug discovery. Sessions focus on research questions, experimental interpretation, and emerging challenges in GPCR science. Are the sessions live or recorded? Masterclass sessions are conducted live with an invited expert. After the event, recordings are added to the Masterclass course library, where Premium Members can access them on demand. Who should join? The Masterclass is designed for GPCR researchers, pharmacologists, and drug discovery scientists working in academia, biotech, and pharmaceutical research. Can I watch sessions later if I miss the live event? Yes. All sessions are recorded and available in the Masterclass course library for Premium Members. Can I watch sessions later if I miss the live event? Yes. All sessions are recorded and available in the Masterclass course library for Premium Members. How do I fit this in my schedule? You can attend the live discussion or watch the recording later. The Masterclass library allows members to revisit sessions at any time. What makes the Masterclass different from reading papers or textbooks? The Masterclass focuses on scientific interpretation and discussion. Experts explain how they think about pharmacological data, experimental design, and discovery challenges—insight that is rarely captured in publications. What happens during the live discussion? Each session begins with a focused presentation from the guest expert, followed by moderated discussion and questions from participants. The format allows deeper exploration of pharmacology concepts than typical conference presentations. Masterclass is included in Dr. GPCR University Live sessions, 200+ on-demand recordings, plus premium intelligence, jobs, events, and a community of GPCR scientists — all in one place. See what it feels like for 14 days. Try University for 14 days — $50 Your professional home in GPCR science. $499/year after trial.

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Dr. Alexander Ball of GeneTex on the recombinant platform and validation strategy behind a challenge to GPCR researchers. Free live webinar, June 25. < Back to Webinars 📅 Thursday, June 25, 2026 at 11:00:00 AM EDT 🤝 Webinar in collaboration with: GeneTex Recombinant Antibodies for GPCRs: A Challenge to the Community Test them in your lab. Tell GeneTex what works and what doesn't. A reagent gap that holds back the biology GPCR activity is targeted by one-third of all FDA-approved drugs. Yet much remains to be learned about how these 800-plus receptors are expressed and how they function in living systems. Part of the gap is biology. Multipass transmembrane proteins are genuinely difficult targets. Part of the gap is the reagents. Reliable antibodies for human GPCRs are scarce, and without them, basic questions about expression and physiological function stay out of reach. Producing specific antibodies for human GPCRs is a formidable job. Expression levels in common cell lines are often low. Identifying an immunoreactive antigen sequence that is specific for a single receptor and detectable across applications is difficult on its own. The literature often disagrees on which antibodies actually work. Proving specificity for the intended GPCR is rarely straightforward. GeneTex is tackling that problem with a high-throughput recombinant antibody platform paired with enhanced validation strategies. The approach has already generated more than 300 recombinant monoclonal antibodies against almost 200 human GPCRs, and the catalog keeps growing. Inside the platform The production workflow is built to detect promising clones early and to hold specificity, scalability, and consistency steady once those clones are selected. Dr. Ball will walk through how the recombinant platform was built, what it takes to produce specific antibodies against multipass transmembrane targets including GPCRs at scale, and how the workflow handles the realities of low endogenous expression and tight specificity requirements. Validation that earns the catalog its place Every antibody is characterized through a prioritized validation set: CRISPR-based knockout and knockdown protocols, endogenous expression detection, cell fractionation, comparable antibody testing, and application-specific testing. When feasible, GeneTex uses VirDTM-GPCR arrays (CDI Labs, Mayagüez, PR), which present a nearly comprehensive library of human non-olfactory GPCRs individually expressed on herpes simplex virion envelopes for cross-reactivity screening. Dr. Ball will walk through each, explain why KO/KD testing is prioritized, and show how the validation data is shared with researchers. The challenge: test them in your lab This is the goal of the Dr. GPCR x GeneTex partnership. GeneTex is offering free samples of the recombinant antibodies to GPCR researchers in exchange for structured feedback, positive or negative. As Dr. Ball puts it in his own words, the primary goal is to get these reagents tested and evaluated by GPCR researchers. That is how a catalog earns the trust of the community, and how the community ends up with reagents it can actually rely on. Dr. Ball will explain how the challenge works, who it is for, and how to request samples. Speaker Dr. Alexander Ball , MD, Senior Scientist, GeneTex, Inc. Dr. Ball has been with GeneTex since 2012 and leads the company's enhanced antibody validation initiative. He earned an M.D. from the University of Southern California School of Medicine and completed internal medicine training at California Pacific Medical Center in San Francisco. He transitioned from clinical medicine to academic research at UC Irvine, where he worked on protein complexes mediating chromosome dynamics. At GeneTex, that background shapes how he thinks about reagent quality. Antibodies are tools scientists depend on, and validation is not optional. Organizers GeneTex GeneTex is a multinational antibody manufacturer founded in San Antonio, Texas in 1997. Since 2020, its recombinant monoclonal antibody facility has produced reagents paired with enhanced validation protocols and a strong emphasis on KO/KD testing. The company's GPCR program is building a comprehensive catalog of recombinant monoclonal antibodies for the human nonsensory and orphan GPCRs. More than 300 recombinant monoclonal antibodies against almost 200 human GPCRs, and growing Prioritized validation: CRISPR KO/KD, endogenous expression, cell fractionation, comparable antibodies, application-specific testing VirDTM-GPCR arrays for specificity screening when feasible Free samples available to GPCR researchers willing to give structured feedback Yearly Glow Strategic Partner in the Dr. GPCR ecosystem Dr. GPCR Dr. GPCR is a nonprofit ecosystem dedicated to advancing GPCR-targeted drug discovery. Through curated intelligence, community engagement, podcasts, webinars, and editorial content, Dr. GPCR connects scientists, tools, and decision-makers across academia and industry, all year round. Previous Webinar Next Webinar Don’t Miss the Next Live Session Dr. GPCR membership gives you access to all upcoming live, interactive webinars. Free. Takes less than a minute to join. Cancel anytime. Sign Up for Free

Gloriam on orphan GPCR biology, GPCRDB, biased signaling, and how the data analysis bottleneck is reshaping receptor pharmacology and drug discovery. << Back to podcast list Strategic Partner(s) David Gloriam: Orphan Receptors, GPCRDB, and the Data Revolution in GPCR Pharmacology GPCRs represent the largest and most pharmacologically important family of membrane receptors, yet a significant portion remain orphans - proteins whose endogenous ligands and physiological roles are still unknown. This conversation explores the intersection of computational biology, cheminformatics, and structural pharmacology through the work of David Gloriam, whose career spans the identification of 26 novel human GPCRs from genome sequence data to the development of GPCRDB, a community resource used by more than 4,400 researchers monthly. Gloriam's research addresses a central challenge in the field: how to move from a bare protein sequence to a pharmacologically characterized receptor with identified ligands, a determined structure, and a plausible role in physiology. The conversation covers the de-orphanization of GPR139 and GPR55, the unresolved promise of biased agonism as a strategy for safer drug development, and the concept of data-accelerated receptor evolution as a framework for engineering receptor-ligand interactions at the residue level. For Gloriam, this work began with a grandmother's cancer diagnosis and an early determination to develop drugs - a goal that led him through the human genome and into a decades-long pursuit of receptors whose functions remain to be written. ABOUT THE GUEST David Gloriam is a professor at the University of Copenhagen's Department of Drug Design and Pharmacology, where he leads a multidisciplinary research group working across data science, computational drug design, pharmacology, and structural biology. His primary research focus is orphan GPCR biology, with particular emphasis on identifying endogenous ligands and physiological roles for receptors discovered during the human genome sequencing era. He maintains and develops GPCRDB, a continuously updated database and tool platform that integrates structural, functional, and ligand data for the entire GPCR superfamily. His group contributed to the de-orphanization of GPR139 and GPR55, including the identification of sub-nanomolar peptide ligand candidates, and has published widely on computational approaches to GPCR drug discovery and receptor classification. SCIENTIFIC THEMES OF THE CONVERSATION Orphan GPCR biology - the challenge of connecting a protein sequence to a physiological function GPCRDB as community infrastructure for integrating and accelerating GPCR research The interdisciplinary de-orphanization pipeline: from bioinformatics to pharmacology to structure The data interpretation bottleneck - how the field's rate-limiting step has fundamentally shifted Biased agonism: from theoretical framework to the challenge of pathway-specific drug design Data-accelerated receptor evolution: engineering GPCR function at the single residue level KEY INSIGHTS FROM THE CONVERSATION The Human Genome as a Discovery Platform When Gloriam joined a bioinformatics group during his master's studies, the first human genome sequence had just become available. Working within that resource, his group identified 26 previously unknown GPCRs in the span of a few years - a pace of discovery that would have been impossible through classical biochemical approaches. The experience established his conviction that computational analysis could function as a genuine primary discovery tool, not merely as support for bench science. De-Orphanization Is a Full-Discipline Effort The process of characterizing an orphan receptor from protein sequence to identified ligand to determined structure cannot be completed within a single lab or a single methodology. Gloriam described the journey of GPR139 as spanning sequence-based phylogeny, database mining for tissue expression, virtual screening, pharmacological assay development, machine learning-guided ligand identification, and finally structural collaboration with external groups. The full arc took more than a decade and required sustained coordination across disciplines that rarely share a lab bench. Taking Over GPCRDB Without a Safety Net When the original GPCRDB team approached retirement, Gloriam chose to carry the resource forward despite holding no tenure and working under a two-year contract. He described it as one of the major single decisions of his career - a bet that the community would respond and the opportunity would justify the risk. The response exceeded his expectations: within years, researchers he had never met were greeting him at conferences by name because of the database. The Bottleneck Has Flipped For most of the history of pharmacological research, generating reliable data was the rate-limiting step. Gloriam argued that this has fundamentally changed: the volume and diversity of available data now far outpaces the field's capacity to analyze and interpret it. This shift places data scientists and computational biologists in a newly central role - not as support for experimentalists, but as the primary constraint to overcome in advancing receptor biology. Biased Agonism Still Needs Its Proof of Concept A drug designed around biased agonism principles received regulatory approval, but its actual functional selectivity has since been questioned - with some researchers arguing it may be a partial agonist rather than a genuinely biased compound. Gloriam identified this ambiguity as symptomatic of a deeper challenge: the field has not yet fully characterized which signaling pathways produce therapeutic benefit and which produce side effects across the GPCR targets most relevant to disease. Until that pathway-level map is built, designing genuinely biased drugs remains a hypothesis in search of its first clean demonstration. Leadership Is a Learnable Skill - If You Seek the Training Gloriam took formal research leadership training before his group was large enough to require it - acting on advice from mentors who recognized that funding panels wanted evidence of leadership readiness alongside scientific merit. He described coaching sessions, national leadership courses, and the deliberate selection of mentors who had recently navigated the specific challenges he was facing. The result was a structured group management model built around four specialized subgroups, each with a senior researcher as daily supervisor - a design that reduced bottlenecks and allowed the science to scale beyond what one group leader could hold. Open Science as the Next Infrastructure Problem Gloriam articulated a vision for GPCRDB as more than a data repository - a shared scientific workspace where researchers could surface big unsolved problems, correspond across institutions, design experiments collectively, and deposit results in a structured format accessible to the entire community. He described the complete characterization of biased signaling pathways across all GPCRs as one such challenge: too large for any single group, and structurally dependent on coordinated community effort that currently has no home. EPISODE TIMELINE Timestamps are AI-generated estimates based on the transcript and may not align exactly with the final edited episode. Verify against the published audio before use. 00:00 Welcome and introduction of David Gloriam 02:23 Career origins - from childhood medicine ambitions to pharmaceutical sciences and bioinformatics 05:34 The human genome treasure hunt - discovering 26 new GPCRs from sequence data 11:55 Orphan GPCRs - years spent chasing receptors with no known function or ligand 13:31 De-orphanizing GPR55 and GPR139 - the full pipeline from sequence to structure 17:21 GPCRDB - origin story, the career-defining decision to take it over, and its growth 23:21 Two frontiers: residue-level receptor function and the unresolved challenge of biased agonism 30:29 Managing a multidisciplinary group of 15 - subgroups, leadership training, and delegation 40:41 What excites Gloriam today - open science models and the long-term vision for GPCRDB 50:01 Career-defining moments, work-life balance, and advice for junior scientists SELECTED QUOTES "Whereas data generation used to be the limiting factor, today it's the analysis and the interpretation and understanding of the data - because we have so much data now, and it's actually our ability to understand it." "The day I stop learning, I might as well die. For me, the actual development - that's the thing. And that's the fun part." "I walked in there and I did the best performance ever. And I walked out and I felt - I think I did it. I did it, yes." "When I come into work and I have a group member that does something better than I do - that's actually what makes me the most proud." About this episode David Gloriam is a Professor in Computational Receptor Biology at the University of Copenhagen where he leads a research cluster for GPCR function and drug discovery and a Pharmaceutical Data Science unit. His group runs the GPCRdb database where ~4,000 researchers each month retrieve reference data and access online tools for analysis, visualization, and experiment design. David obtained his Ph.D. from Uppsala University in Sweden where he worked on the bioinformatic identification of 24 novel human G protein-coupled receptors. He later identified physiological hormones of such under characterized ‘orphan’ receptors and functional probes for a range of receptors. He completed two postdocs in the UK at the EMBL-European Bioinformatics Institute and GlaxoSmithKline . In 2018 he joined the University of Copenhagen, where he has received an ERC Starting Grant, Lundbeck Foundation Fellowship, and Novo Nordisk Foundation Ascending Investigator awards. Dr. Gloriam is a corresponding member of the Nomenclature Committee of the International Union of Pharmacology (IUPHAR). He is one of the coordinators of recommendations to describe ligand bias towards signaling probes and safer drugs. His group recently developed an online resource of biased ligands and pathway effects to advance the biased signaling field. Join me a learn more about David’s work, his career trajectory, and GPCRdb. Dr. David E. Gloriam on the web LinkedIn ResearchGate Twitter Google Scholar Computation Receptor Biology- Gloriam Group GPCRdb Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Terry Hebert on why challenge trials weren't ready, what it takes to hold a GPCR signaling lab together during a pandemic, and the BRET-based beta-1 adrenergic paper that landed in lockdown. << Back to podcast list Strategic Partner(s) Dr. Terry Hebert: A Pharmacologist Thinking Through Lockdown This resilience conversation with Dr. Terry Hebert was recorded in spring 2020, when Montreal was the national epicenter of the COVID-19 pandemic and every non-essential bench in the country was shut. The discussion moves across three scientific registers: the practical mechanics of holding a GPCR signaling lab together remotely; the continuity of receptor pharmacology work already in the pipeline before the shutdown, including a newly accepted BRET-based platform for beta-1 adrenergic receptor signaling built with the Bouvier lab; and a pharmacologist's reasoning about the then-unresolved question of whether human challenge trials were an ethical shortcut to a SARS-CoV-2 vaccine. Dr. Hebert's argument — that challenge trials depend on a reliable therapeutic the field did not yet have — sits at the intersection of drug discovery logic and public health ethics, and illustrates how GPCR scientists reason about pharmacology problems well outside their primary receptor. For Dr. Hebert, the conversation is also about what he had to let go of: the assumption that a lab, once built, runs on its own inertia. About the Guest Dr. Terry Hebert is a professor at McGill University in Montreal, where his lab studies G protein-coupled receptor signaling. His research spans BRET-based assay platforms for characterizing signaling downstream of specific GPCRs, the transcriptional regulation of signaling components as an underappreciated axis of pharmacological modulation, and long-running collaborations on beta-adrenergic receptor biology with the Bouvier lab and others. His work is grounded in careful assay development and a conviction that the signaling space around a receptor is richer than single-pathway readouts suggest. Scientific Themes of the Conversation Lab continuity during institutional shutdown — What it takes to maintain scientific output when the physical lab is closed and every operation has to happen remotely. BRET platforms for GPCR signaling — The role of resonance-energy-transfer-based assays in capturing signaling downstream of specific receptors, with the beta-1 adrenergic receptor as a worked example. Challenge trials and the therapeutic floor — Why the ethics of accelerating vaccine trials depend on having an adequate treatment for the disease under study. Vaccine development at scale — How to read a landscape of 90+ parallel vaccine candidates without confusing breadth of effort for probability of success. Mentorship under isolation — The practical and emotional work of keeping graduate students — especially international students far from their families — connected to a lab that has gone quiet. Pandemic preparedness as a scientific failure — The gap between what infectious disease researchers had been warning about and what institutions were actually ready to do. Key Insights from the Conversation Challenge trials don't work without a reliable drug. Dr. Hebert's core pharmacology argument is that proposing a challenge trial — where volunteers receive placebo or active virus — is ethically unworkable without a therapeutic that can rescue the ones who get sick. His position is that the drug problem has to be solved, or at least bounded, before the vaccine trial design can responsibly change. 90 vaccine candidates is a number about effort, not probability. The conversation pushes against the comfort of large numbers. A field running 90 parallel vaccine trials is a field hedging under uncertainty, not a field with 90 independent chances of success. Dr. Hebert is hopeful but careful about the distinction. BRET platforms carry work forward when the lab can't. The beta-1 adrenergic receptor paper — a BRET-based platform for capturing downstream signaling, built with the Bouvier lab — illustrates how assay-development projects remain productive when benchwork stops. The experimental data was in hand before the shutdown; the intellectual work of writing, reviewing, and revising kept going regardless. A lab is a social infrastructure, not just a physical one. Weekly Monday lab meetings, Friday journal clubs, daily Slack and Zoom contact, a faculty-vs-student trivia night — the lab's continuity came from translating routines, not suspending them. The most fragile link in the system was the isolation of international students away from their families. Reopening is a puzzle about labs, not benches. The hardest logistical problem isn't social distancing within a single lab — it's social distancing between labs sharing a floor, shared equipment, and a public transit system that funnels everyone through the same bottleneck. The warnings were there. Dr. Hebert's reflection on preparedness is quiet but pointed: the scientific community had been warning about this for years. The failure wasn't epistemic — it was institutional. And that failure is what will cost the most, borne hardest by the people least cushioned against it. The next one is coming. The most forward-looking moment in the conversation is also the most sober. This disease, for all its damage, is survivable for most people. The next one might not be. The open question is whether the system will have learned anything by then. Episode Timeline Timestamps were generated using AI for readability. 00:00 Welcome and Dr. GPCR Summit 2020 announcement 01:49 Check-in with Dr. Hebert — shutdown, reopening plans, and Montreal as epicenter 03:06 Paper acceptances, thesis writing, and 30 hours of Zoom teaching in one month 04:29 The beta-1 adrenergic BRET paper and a review on transcriptional regulation as a drug target 05:22 Lab meetings, journal clubs, and the Slack/Zoom scaffolding 06:12 Student wellbeing and the puzzle of reopening a shared floor 07:16 Why challenge trials aren't ready — and the remdesivir question underneath them 08:52 When pandemic infrastructure breaks down at national scale 10:16 Lessons for the next one, and the shape of the new normal Selected Quotes "So we made a decision a month and a half ago to kind of stop going to the lab. Montreal being the epicenter of the disease in this country — we don't regret that decision now." "I don't think [challenge trials] are a good idea because we don't really have good drugs to deal with the disease when people get sick. If we have a way to control the disease and keep people from getting really sick, I think we can go to challenge trials more rapidly." "Honestly it could be worse, right? This disease, most people survive. When the next one comes, let's hope we learn something from this one." "Those are the people we have to protect, not big corporations who, you know, are probably in a sense part of the cause. Globalization is not something that is without its consequences here." About this episode Dr. Terry Hébert is a Professor within the Department of Pharmacology & Therapeutics at McGill University. Much of his work is based on GPCR signaling in the context to cardiovascular diseases. In this special episode of the Dr.GPCR podcast , we re-connected with Dr. Terry Hebert to chat about how he and his team has been adapting to the new reality of working remotely. Terry tells us about the importance of adapting, communicating, and being mindful of those around us. Dr. Terry Hébert on the web Terry Hébert | Institute of Health Sciences Education Hébert Lab LinkedIn Hébert Lab The GPCR Consortium PubMed Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. GPCR Team About Dr. Yamina Berchiche Dr. Yamina A. Berchiche is the founder of Dr. GPCR, an ecosystem designed to bring together stakeholders interested in using G-Protein Coupled Receptors (GPCRs) that control virtually everything in the body as drug targets. The mission of Dr. GPCR is to accelerate GPCR drug discovery by sharing the latest research and technology advances in the field and providing exposure to scientists through the Dr. GPCR podcast. Dr. Berchiche obtained her Master’s and Ph.D. in Biochemistry at the University of Montreal in Canada before training at Rockefeller University in New York and the National Institutes of Health in Bethesda, Maryland. She developed expertise over the past two decades studying structure/function relationships of GPCRs using live-cell bioluminescence resonance energy transfer (BRET). Her work focused on chemokine receptors, members of the GPCR family that control cell movement in the body. Dr. Yamina Berchiche on the web Website LinkedIn Facebook Twitter ResearchGate PubMed Google Scholar Dr. GPCR About Dr. Shivani Sachdev Dr. Sachdev is an early career researcher in the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. Her research centers on developing nanobody-ligand conjugates to target GPCRs, with a focus on receptors relevant for treating osteoporosis, diabetes, and pain. She received her undergraduate degree in Biotechnology from KIIT University in India. She subsequently joined Professor Mark Connor's laboratory at Macquarie University in Australia. Dr. Sachdev pursued Ph.D. in the same lab where she investigated the molecular pharmacology of cannabinoid receptors. She is also very active within the pharmacology community and currently serves on the editorial board of the British Journal of Pharmacology. Given her expertise in GPCR pharmacology and scientific communication, she is poised to make valuable contributions to the field and expand our understanding of GPCR signaling. Dr. Shivani Sachdev on the web NIDDK ReseachGate Google Scholar LinkedIn Twitter Dr. GPCR About Dr. Inês Pinheiro PharmD by training and Ph.D. candidate in Hartley's lab at the University of Geneva. As a young researcher fascinated by chemokine receptors, molecular pharmacology, drug discovery, and immuno-oncology. Dr. Inês Pinheiro on the web LinkedIn University of Geneva Twitter Dr. GPCR About Dr. Monserrat Avila Zozaya I did a PhD in cell biology at CINVESTAV, Mexico. During that time, I investigated the effect of lung cancer-related mutations in the GAIN domain of the Latrophilin 3 receptor. My long-term interest is focused on understanding the mechanisms mediated by GPCRs at the cellular communication level. Dr. Monserrat Avila Zozaya on the web LinkedIn Antony Boucard Lab Dr. GPCR About John Azietaku John Teye Azietaku,PhD is a trained pharmacist, holding a Ph.D. in Drug Discovery Biology and Pharmacology from Monash University. Currently serving as a Post Doctoral research fellow at Monash University, John plays a pivotal role in the pharmacological screening of compounds for a commercial drug discovery program. With prior industry experience as a Clinical Research Associate at IQVIA and regulatory officer at the Food and Drug Authority (FDA) in Ghana, John has a proven track record of ensuring compliance with protocols and regulatory standards. Driven by a passion for advancing drug development, John is committed to leveraging his expertise to enhance healthcare outcomes and contribute to the growth of the pharmaceutical and biotech industry. John Azietaku on the web LinkedIn Dr. GPCR About Ya-Tzu Li Ya-Tzu is a Master's student at the University of South Florida, utilizing large-scale virtual drug screening to identify agonists and antagonists targeting Class A GPCRs. Since beginning her undergraduate studies, she has used computational methods like molecular dynamics simulations and free energy landscape analysis to understand the signaling pathways and activation mechanisms of the Dopamine D3 receptor and the CXCR4-CXCL12 complex. In August, Ya-Tzu will continue her academic and research pursuits by beginning her PhD training in Medical Science at USF, aiming to further contribute to the field of medical pharmacology. Ya-Tzu Li on the web LinkedIn Dr. GPCR About Cam Sinh Lu Cam Sinh Lu is a PhD student at Monash Institute of Pharmaceutical Sciences, Monash University, with a deep interest in understanding drug-receptor interactions. With an immense passion for molecular pharmacology, his research focuses on elucidating the molecular basis of membrane protein signalling using quantitative assays and molecular modelling. Further down the track, he aims to apply this knowledge to develop novel chemical treatments for neuronal and cardiovascular diseases. Cam Sinh Lu on the web LinkedIn Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Cheloha builds nanobody-GPCR ligand conjugates that rescue weak peptides, engineer receptor selectivity, and probe endosomal signaling at NIH. << Back to podcast list Strategic Partner(s) Ross Cheloha: Nanobody-GPCR Conjugates and the Engineering of Receptor Selectivity The parathyroid hormone receptor sits at the intersection of calcium homeostasis, bone metabolism, and a set of pharmacological questions that have resisted clean resolution for decades. How does receptor conformation shape the duration of downstream signaling? Why do some ligands continue activating from the endosome while others don't? And can selectivity for one receptor subtype be engineered without redesigning the ligand from scratch? Ross Cheloha approaches these questions from a chemical biology perspective - using synthetic peptide analogs, camelid single-domain antibodies (nanobodies), and bifunctional conjugates that split the binding event into two independently tunable pieces. In this conversation, he describes how attaching a moderately active peptide to a receptor-targeted nanobody can boost potency by up to 10,000-fold, and how the selectivity of the nanobody - not the ligand - is what engineers receptor subtype specificity. For Cheloha, the motivation traces back to a habit he carried from childhood: writing reports on exotic diseases and what scientists were doing to treat them. The experiment that mattered most was not a drug candidate or a clinical advance - it was a designed conjugate that worked when there was no clear reason it had to, every control behaving exactly as expected. About the Guest Ross Cheloha is a tenure-track investigator at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health. His research combines peptide chemistry, chemical biology, and nanobody engineering to build mechanistic tools for studying GPCR signaling, with a particular focus on the parathyroid hormone receptor and its downstream consequences for calcium homeostasis and bone biology. Trained in the Gelman lab at the University of Wisconsin-Madison and later in the Ploegh lab at Harvard Medical School and Boston Children's Hospital, he developed methods for covalently functionalizing camelid single-domain antibodies with synthetic ligands to probe receptor conformation, endosomal activity, and the duration of signaling responses. His work has demonstrated that nanobody-ligand conjugates can rescue pharmacologically weak peptides, engineer receptor subtype selectivity, and open mechanistic questions that conventional ligand design cannot easily address. Scientific Themes of the Conversation Peptide analog engineering and the stabilization of GPCR ligands using non-natural amino acids Receptor conformation selectivity: G-protein coupled versus uncoupled states and their downstream consequences Camelid single-domain antibodies (nanobodies) as a platform for GPCR chemical biology Nanobody-ligand conjugates as bifunctional tools for potency rescue, selectivity engineering, and mechanistic dissection Duration of signaling and endosomal GPCR activity: what wash-and-measure paradigms have been missing Tissue-specific receptor targeting and the pharmacological logic of reducing GPCR side effect profiles Key Insights from the Conversation 1. Conformation selectivity changes the duration of the signal PTH receptor exists in G-protein coupled and uncoupled states, and peptide analogs incorporating non-natural amino acids show differential affinity for each conformation. The analogs that preferentially bind the uncoupled state produce markedly prolonged signaling responses - in cells and in animal experiments - compared to ligands that do not. The biology may have been using this distinction all along: two natural ligands for the same receptor already show subtly different conformation preferences and different physiological profiles in vivo. 2. One nanobody, four orders of magnitude Connecting a short, weakly active PTH fragment (11 amino acids, approximately 100 nanomolar potency) to a receptor-targeted nanobody produced sub-nanomolar potency in cell-based assays - an improvement of up to 10,000-fold from a single engineering step. The working model is that the nanobody anchors the conjugate at the receptor surface, positioning the ligand for activation that would otherwise be too transient to drive a strong response. The selectivity comes from the nanobody's binding specificity, not from chemical modification of the peptide itself. 3. Selectivity without redesigning the drug PTH 1-34 activates both PTHR1 and PTHR2 with high potency, and engineering subtype selectivity through chemical modification of the peptide is technically demanding. Attaching a short PTH fragment to a PTHR1-selective nanobody produces a ligand selective for that subtype; the same fragment attached to a PTHR2-selective nanobody redirects it entirely. The implication generalizes: wherever a selective nanobody exists for a GPCR target, it can be used to introduce specificity into an otherwise promiscuous ligand without restructuring the pharmacophore. 4. Endosomal signaling is being missed Conventional GPCR assay design - stimulate, wash, measure endpoint - systematically misses signaling that continues after receptor internalization into the endosome. Cheloha's position is that the standard assumption linking tighter binding to longer signaling is incomplete. Endosomal activity is a distinct mechanistic process, and the tools to dissect it - bifunctional conjugates with independently tunable affinity components - are not available with conventional single-piece ligands. This is the central mechanistic priority he is bringing to his NIH lab. 5. Tissue-specific targeting as a strategy for reframing side effects The primary dose-limiting side effect of PTH-based therapies is hypercalcemia, driven in part by receptor activity in kidney tissue rather than bone. Connecting a ligand to a tissue-targeted nanobody could restrict receptor activation to bone and reduce unwanted calcium release. The pharmacological logic is sound, and the engineering framework to test it exists. Whether it holds in vivo remains to be demonstrated - Cheloha is careful to say so - but it represents a genuinely new angle on a long-standing problem in PTH pharmacology. 6. The experiment that had no reason to work - and did Among three scientific aha moments Cheloha described, the one with the clearest forward momentum was the first successful nanobody-PTH conjugate - designed not because a clear rationale existed, but because he wondered whether it was possible. No hypothesis guaranteed the result. Every positive and negative control performed exactly as designed. The conjugate worked. That single experiment, Cheloha said, opened more mechanistic doors than anything he had produced before - and it came directly from experience-built intuition rather than hypothesis-first design. Episode Timeline Timestamps are AI-generated from the transcript and are approximate. Verify against the final edited video before publishing. 00:00 Introduction 01:58 From pharmacy school to chemical biology: how the research path took shape 08:12 Academia versus industry - why freedom to ask non-translatable questions matters 09:43 The academic job search: 65 applications, six interview trips, and landing NIH 14:20 How a peptide chemist found the PTH receptor - and a collaborator who changed everything 17:20 Non-natural amino acids, protease stability, and receptor conformation selectivity 21:40 PTH receptor pharmacology: calcium spikes, bone biology, and why long-acting isn't always better 23:22 A detour into immunology and the discovery of camelid nanobodies 25:45 The first nanobody-GPCR ligand conjugate and an unexpected 10,000-fold potency gain 30:32 Engineering receptor subtype selectivity without redesigning the pharmacophore 36:10 Mechanistic priorities at NIH: endosomal signaling and duration of signaling 40:25 Are GPCRs still a good drug target? Biased agonism, endosomal signaling, and what remains 47:13 Three aha moments: first data, an email from Gardella, and the conjugate that worked Selected Quotes "I just thought of something - hey, I wonder if this would work. There was not necessarily an underlying scientific rationale for trying this. I wasn't thinking this is going to be a new drug. I just thought of something and said, I wonder." "I was convinced that I designed something that worked where it was not at all obvious that it was going to work. And that just opened up so many doors." "I don't think tight binding equals longer signaling is necessarily the whole story. I think in large part it's been missed." "Anything you can contribute to that end is hopefully going to provide a step forward in understanding disease and treating disease. The freedom and creativity - that's what I was really attracted to." About this episode Dr. Ross Cheloha is an Investigator at the National Institutes of Health in the Laboratory of Bioorganic Chemistry in Bethesda, MD, where he started in October 2020. He completed his postdoctoral training at MIT and Harvard Med School in the lab of Hidde Ploegh , where he developed new applications of single-domain antibodies (nanobodies). He earned his Ph.D. in Chemistry at the University of Wisconsin-Madison in the lab of Sam Gellman on the study of analogs of the GPCR peptide ligand parathyroid hormone. Work in his independent laboratory is focused on developing new pharmacological tools via chemistry and protein engineering to interrogate GPCR signaling. Ross and I chatted about his work and transition to an independent investigator; join me to learn more about class B GPCRs and Dr. Cheloha’s work. Dr. Ross Cheloha on the web NIDDK Cheloha Lab Google Scholar LinkedIn Twitter ResearchGate Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Bender uses virtual docking to find chemical probes for orphan GPCRs - receptors biology can't study because the tools don't exist yet. << Back to podcast list Strategic Partner(s) Brian Bender: Computational Probes for Orphan GPCR The GPCR superfamily contains hundreds of receptors that cannot be experimentally studied because no usable chemical probe exists for them. Finding an endogenous agonist - when one is even known - is rarely sufficient: a large peptide or lipidated compound may activate a receptor in vivo but is useless as a cell-based tool. This gap is one of the defining bottlenecks in receptor pharmacology, and closing it one receptor at a time will take decades. Brian Bender's work addresses this problem computationally. At UCSF, he develops structural models of GPCRs using sparse experimental data - combining restraints from X-ray crystallography, NMR, and electron paramagnetic resonance spectroscopy - and applies large-scale virtual docking to identify candidate chemical probes across the understudied GPCR landscape. His approach scales across the family rather than stopping at individual targets. Bender trained at the bench before moving fully into computation, and that transition was not planned. A stalled labeling project on the NPY2 receptor during his PhD at Vanderbilt redirected his entire trajectory - and eventually revealed that the patterns connecting receptors across the GPCR family were more interesting than any single structure. ABOUT THE GUEST Bender is a postdoctoral fellow at UCSF working at the intersection of computational structural biology and receptor pharmacology. His research focuses on predicting GPCR structural ensembles from limited experimental data and using virtual docking to identify chemical probes for orphan and understudied receptors. He trained as a structural biologist at Vanderbilt University, working with X-ray crystallography, protein NMR, and electron paramagnetic resonance before transitioning to computation during his PhD work on the NPY2, NPY1, and ghrelin receptors. His fluency in both bench and computational languages shapes how he builds models and how he interprets the experimental data that constrains them. SCIENTIFIC THEMES OF THE CONVERSATION Computational structural modeling of GPCRs from sparse and low-resolution experimental data Virtual docking as a strategy for pan-GPCR chemical probe discovery The orphan receptor problem - why endogenous agonists are not sufficient tool compounds Bench-to-computation transitions and what fluency in both languages enables Family-wide approaches to receptor pharmacology versus single-receptor studies Building scientific community at the early-career stage KEY INSIGHTS FROM THE CONVERSATION The probe gap is a biological bottleneck, not just a chemical one Without a usable chemical probe, a GPCR cannot be studied pharmacologically in a cell-based setting. Even when an endogenous agonist is known, it may be a large peptide or lipidated compound that cannot be practically dosed in vitro. Bender's work targets this gap directly - arguing that de-orphanizing a receptor biochemically and making it experimentally tractable are two separate problems. Virtual docking changes the scale equation Individual bench approaches to identifying tool compounds can take months to years per receptor. Virtual docking screens compress that timeline significantly and can be applied across many receptors in parallel. Bender frames this not as a replacement for bench pharmacology but as the only realistic path to coverage across the full orphan GPCR landscape. The failed experiment that built a career Bender's NPY2 labeling project - designed to generate DEER spectroscopy distance restraints for conformational modeling - never yielded usable data. Rather than a setback, it became a forced pivot into computation at precisely the moment his modeling skills were becoming sufficient to carry a project independently. The stalled experiment was the origin point of the approach he now applies at family scale. Bench experience as a modeling guardrail Knowing what an EC50 means experimentally, or what a Bmax implies about receptor expression, changes how computational restraints are built and applied. Bender credits his time at the bench with preventing the kind of over-interpretation that models built purely from computational intuition can produce - a perspective that shapes how he translates collaborators' data into structural constraints. The eureka of the whole family Months of manually reading sequence alignment tables - before Bender could write the scripts to automate the analysis - produced an unexpected result: structural and sequence patterns connecting receptors across GPCR subfamilies that he had not been told to look for. That period of laborious, close-range data inspection became the conceptual foundation of his pan-GPCR approach, and the moment he understood that one receptor was not enough. Connecting scientists is its own form of science Bender's role co-chairing the Gordon Research Seminar on Molecular Pharmacology is not separate from his scientific work - it is continuous with it. He articulates that the lateral connections formed at early-career conferences, between people who will be colleagues for the next 20 years, are a different kind of scientific output but no less consequential for where the field goes next. EPISODE TIMELINE Timestamps generated with AI assistance and are approximate. They may vary slightly from the final edited version. 00:00 Introduction 01:31 From structural biology to GPCR computation - how the path began 05:47 Modeling GPCR conformational ensembles from sparse data 07:44 Origin moment - a lab notebook at age 8 11:53 The NPY2 labeling project that stalled - and the pivot it forced 17:22 From NPY2 to ghrelin - when one receptor becomes a family question 19:54 Joining UCSF and building the pan-GPCR docking pipeline 21:53 Co-chairing the Gordon Research Seminar on Molecular Pharmacology 47:42 Why orphan receptors need chemical probes, not just endogenous agonists 52:54 Bench fluency as a guard against over-interpreting computational models 58:16 Advice for early-career scientists on connecting with the field 01:02:48 Eureka moment - patterns across the whole receptor family, read by eye SELECTED QUOTES "Are they crazy? Do they know the gold mine that they just gave me?" "It's hard to ever leave the GPCR world once you go into it, just because the longer you stay in it, the more you realize we still don't know in this family." "Taking time to think about what you're doing is way more valuable than just trying to do the next ten million experiments all at once." "I have to go into more receptors. I can't stay with just the one." About Dr. Brian Bender Dr. Bender completed his undergraduate studies at Colgate University in upstate New York with a degree in Biochemistry. Between undergraduate and graduate school Brian worked as a technician in an academic lab before moving to Nashville, TN for graduate work at Vanderbilt University where he joined the Department of Pharmacology. Brain’s work there primarily focused on structure prediction of GPCRs from sparse experimental data. He then moved to the University of California in San Francisco to continue his training as a postdoctoral researcher where he used structural models of GPCRs to virtually screen large compound libraries with the goal of finding new chemical matter to probe understudied and orphan receptors. Brian is involved in organizing the GRC/GRS Molecular Pharmacology meeting, which has been postponed to 2023. Brian is one of the organizers of the upcoming Transatlantic ECI GPCR Symposium . Dr. Brian Bender on the web LinkedIn Twitter ResearchGate Dr.GPCR Member Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

A conversation with Dr. Tore Bengtsson on β₂-adrenergic receptor signaling, muscle metabolism, and how GPCR pharmacology can lead to new therapies for metabolic disease. << Back to podcast list Strategic Partner(s) Tore Bengtsson: Rethinking β₂-Adrenergic Signaling in Metabolic Disease Scientific Abstract This conversation with Dr. Tore Bengtsson , professor of physiology at Stockholm University, explores how β-adrenergic receptor signaling can be reimagined to address metabolic disease, muscle physiology, and energy balance. Dr. Bengtsson’s research spans sympathetic nervous system signaling, brown adipose tissue biology, and skeletal muscle metabolism—fields deeply connected to obesity, type 2 diabetes, and metabolic health. A central theme of the discussion is the pharmacology of the β₂-adrenergic receptor , a GPCR traditionally associated with bronchodilation but increasingly recognized for its broader physiological roles. Dr. Bengtsson describes how classical β₂ agonists stimulate muscle growth and metabolic changes but are limited by receptor desensitization. His work focuses on developing novel β₂-adrenergic ligands that selectively engage signaling pathways without triggering rapid desensitization, enabling sustained metabolic effects. The conversation also examines how GPCR signaling is far more complex than a single downstream pathway. Instead, receptors integrate multiple signaling outputs, temporal dynamics, and interactions with other pathways to shape physiological outcomes. Dr. Bengtsson discusses how understanding this signaling complexity opens opportunities to design drugs that promote beneficial metabolic responses such as muscle growth and increased energy expenditure. Listeners gain insight into how basic GPCR pharmacology can translate into therapeutic strategies targeting metabolism, aging, and metabolic disease. About the Guest Dr. Tore Bengtsson is a professor of physiology at Stockholm University whose research focuses on sympathetic nervous system signaling, metabolic regulation, and skeletal muscle physiology. His work investigates how β-adrenergic receptors regulate energy metabolism, muscle growth, and glucose homeostasis. Dr. Bengtsson began his research career studying brown adipose tissue under the mentorship of Dr. Barbara Cannon and Dr. Jan Nedergaard, pioneers in thermogenesis research. His laboratory now explores how β₂-adrenergic receptor signaling can be manipulated to influence metabolism and muscle physiology. He is also an entrepreneur and founder of biotechnology companies translating GPCR pharmacology into therapeutic development. Scientific Themes of the Conversation β-adrenergic receptor pharmacology and signaling bias Sympathetic nervous system control of metabolism Brown adipose tissue and thermogenesis Skeletal muscle metabolism and glucose homeostasis GPCR signaling complexity and pathway selectivity Translating receptor pharmacology into metabolic therapeutics Key Insights from the Conversation A Childhood Physiological Experiment Sparked a Scientific Career Dr. Bengtsson recounts a formative experience when his father pushed him into icy water as a child to demonstrate survival in cold conditions. The intense physiological response—an adrenaline surge and rapid adaptation to cold—sparked his lifelong fascination with sympathetic nervous system signaling and stress physiology. Stress Is Not Always Negative A recurring theme in the discussion is that physiological stress is often misunderstood. Short bursts of stress—whether exercise, cold exposure, or sympathetic activation—can trigger adaptive responses that improve metabolic function and resilience. Muscle Is Central to Metabolic Health While brown fat has received considerable attention, Dr. Bengtsson emphasizes the dominant role of skeletal muscle in metabolic regulation. Approximately 75% of glucose disposal occurs in muscle, making muscle physiology central to metabolic diseases such as type 2 diabetes. Classical β₂ Agonists Have a Fundamental Limitation Traditional β₂-adrenergic agonists can stimulate muscle growth and fat loss but lose effectiveness over time due to receptor desensitization. This pharmacological limitation prevents their long-term use for metabolic therapies. GPCRs Do Not Produce a Single Signal Dr. Bengtsson highlights that GPCR signaling is inherently multidimensional. Activation of a receptor can generate multiple signaling pathways, and different ligands can bias signaling toward specific outcomes. Understanding this complexity is essential for modern drug discovery. Absence of a Signal Can Be a Discovery One of Dr. Bengtsson’s key scientific breakthroughs came from an unexpected experimental result: glucose uptake without detectable cAMP signaling. Rather than dismissing the result as an error, this observation led to the realization that β₂ signaling could be separated into distinct pathways. Scientific Discovery Requires Intellectual Independence Dr. Bengtsson advises young scientists to shift from passively following instructions to actively questioning experiments and interpretations. True scientific thinking begins when researchers take intellectual ownership of the questions they pursue. Episode Timeline 00:00 Introduction and research focus of Dr. Bengtsson 03:00 A childhood experiment that sparked interest in physiology 07:00 Cold exposure, sympathetic signaling, and brown fat research 10:00 β₂-adrenergic receptors and muscle physiology 15:00 Exercise, metabolism, and pharmacological modulation of muscle growth 17:30 Early research on brown adipose tissue and thermogenesis 22:30 Translating academic discoveries into biotech companies 25:00 GPCR signaling complexity and biased signaling 36:00 A key experimental observation leading to a new drug concept 38:30 Advice for young scientists and intellectual independence Selected Quotes “You will not know what happens before you do the experiment.” “People think a receptor produces one signal. In reality, a receptor produces many signals.” “Sometimes the most important discovery is when a signal is missing.” “You have to move from being told what to do to thinking for yourself.” Full Transcript (Formatted for readability — full transcript preserved) Yamina Berchiche: Hello, everyone. This is Yamina from Dr. GPCR. And today I'm very excited to have with me Dr. Tore Bengtsson. Dr. Bengtsson: Tore Bengtsson. And you got it right. Yamina Berchiche: I'm happy to have you on. For those who don't know, we've been chasing each other and postponing this conversation several times. I'm very excited that we're finally able to do it today. Dr. Bengtsson: Thank you. I'm very happy to be here. Yamina Berchiche: Let's start at the beginning. Could you introduce yourself and tell us about your research? Dr. Bengtsson: I'm a professor in physiology at Stockholm University. I've been working with pre-diabetes, type 2 diabetes, obesity, and the mechanisms behind these diseases for about 25 years. I'm especially interested in β-adrenergic receptors because I believe they regulate far more physiological processes than people typically assume. I'm also an entrepreneur. I've started several companies. One is Sigrid Therapeutics, which focuses on digestion and metabolic regulation. Another company, Atrogi, is based on our research on β₂-adrenergic receptors and the development of new drugs. We’ve already completed Phase I clinical trials and are preparing for Phase II. Yamina Berchiche: If you were not a scientist, what would you be doing? Dr. Bengtsson: I think I might have been a historian or a writer. I like storytelling. I'm very interested in Viking runes and ancient rune stones in Scandinavia. I can actually read runic inscriptions, and I find it fascinating to interpret what these stones tell us about history. Yamina Berchiche: How did you become a scientist? Dr. Bengtsson: I'll tell you a story I don't share very often. When I was about ten years old, I lived on an island in the Stockholm archipelago. My father and I went ice skating frequently during the winter. One summer he asked me: “What happens if you fall through the ice?” I said I didn't know. He replied: “We should test it.” Months later, during winter, he cut a hole in the ice. I asked what he was doing. He said he was catching a big fish. Suddenly he pushed me into the icy water. I went under, looked up at the hole in the ice, and quickly swam out. I remember the intense adrenaline surge. My body reacted instantly. I wasn't even cold at first. Walking home later I started to freeze, but in that moment I experienced a powerful physiological response. That event sparked my lifelong fascination with sympathetic nervous system activation. Yamina Berchiche: So your father pushed you into science quite literally. Dr. Bengtsson: Yes — and into physiology. Yamina Berchiche: And that connects directly to your later work on brown fat and sympathetic signaling. Dr. Bengtsson: Exactly. I've spent many years studying brown adipose tissue and how sympathetic activation stimulates thermogenesis. Later I became increasingly interested in skeletal muscle metabolism and how β₂-adrenergic signaling affects muscle growth and glucose metabolism. Yamina Berchiche: Could you talk about how β₂-adrenergic signaling relates to muscle growth? Dr. Bengtsson: For many years it's been known that β₂ agonists can stimulate muscle growth and reduce fat. This has been observed in athletes and even in livestock production. But traditional β₂ agonists lose effectiveness over time because the receptor becomes desensitized. The body adapts, requiring higher doses. That makes them unsuitable as long-term therapeutic drugs. So about 15–20 years ago I began working on the idea that we need a new type of β₂ agonist—one that activates the receptor differently and avoids desensitization. That’s what we’ve now achieved with new compounds that stimulate the receptor in a novel way. Yamina Berchiche: You mentioned something very important earlier: GPCRs don’t produce a single signal. Dr. Bengtsson: Yes. Traditionally people thought receptor activation leads to one downstream pathway. But GPCRs activate multiple signaling pathways simultaneously. Different ligands can bias signaling toward different pathways. That means we can design compounds that favor beneficial physiological responses while avoiding unwanted effects. That is exactly what makes GPCR pharmacology so fascinating and powerful. Yamina Berchiche: You mentioned an important experimental moment that led to your drug concept. Dr. Bengtsson: Yes. A doctoral student ran an experiment measuring glucose uptake. The compound produced strong glucose uptake but almost no cAMP signaling. She thought the experiment had failed. But I realized this might be something important: glucose uptake without cAMP. And that turned out to be correct. That observation opened the door to separating signaling pathways and designing new β₂ ligands. Yamina Berchiche: What advice would you give to young scientists? Dr. Bengtsson: Young scientists often follow instructions without asking why. Real science begins when you take control of the question. You must move from being told what to do to thinking independently. You have to be in the driver's seat of your own thinking. Yamina Berchiche: That’s a powerful message. Dr. Bengtsson: And another lesson I learned from my wife: success often depends not just on knowledge but on understanding how other people think. Science is not just experiments. It's communication, persuasion, and collaboration. Yamina Berchiche: Dr. Bengtsson, thank you very much for the conversation. Dr. Bengtsson: Thank you. This was great. Yamina Berchiche: Bye. Dr. Bengtsson: Bye-bye. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

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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 Scientific Abstract A female mosquito that has just fed on human blood stops seeking humans for three to four days while she digests that meal and develops eggs. Laura Duvall's lab has traced this suppression to a specific neuropeptide Y family receptor, one she first identified as a postdoctoral fellow and has since found expressed almost exclusively in an unexpected tissue, the mosquito rectum. Her group works at the intersection of neuropeptide signaling, behavioral genetics, and vector biology in Aedes aegypti, the species responsible for transmitting Zika, dengue, and chikungunya. This conversation traces her path from circadian rhythm research in Drosophila to mosquito behavior, and lays out why a receptor built to regulate host seeking and mating might offer a way to interrupt pathogen transmission at its source rather than treating each disease separately. What pulls Duvall back to this receptor personally is its apparent conservation: the same NPY family receptor she found in mosquito gut tissue has a close relative in the human colon, doing a job no one has fully worked out yet. About Laura Duvall runs a research lab in the Department of Biological Sciences at Columbia University, where her group studies how mosquitoes regulate innate behaviors, primarily blood feeding and mating. She trained in neuroscience during her PhD, characterizing how pigment dispersing factor and related GPCRs coordinate circadian clock cells in the Drosophila brain, then moved into mosquito research as a postdoctoral fellow with Leslie Vosshall at Rockefeller University. Her lab uses CRISPR based gene editing, automated behavioral assays, and video tracking to study neuropeptide Y family receptors in Aedes aegypti, with a particular focus on host seeking suppression and female mating receptivity. Scientific Themes of the Conversation - Neuropeptide Y family receptors as conserved regulators of feeding and reproductive behavior - Host seeking suppression in blood fed females as a druggable behavioral switch - Cross species pharmacological crosstalk between human and mosquito receptors - Unexpected receptor localization outside canonical neuronal tissue - Automated, experimenter free behavioral assays as a response to human bias in the data - Vector behavior disruption as an alternative to pathogen specific therapeutics Key Insights from the Conversation A single gene deletion reopened a closed behavioral window. Duvall's lab used CRISPR to mutate the receptor she had identified as important for host seeking suppression. Blood fed females that should have lost interest in humans for several days continued seeking hosts anyway. Watching one gene override such a strong, evolutionarily tuned behavioral drive was, in her words, almost magical. A neuropeptide receptor turned up in a tissue no one expected. When the lab went looking for where this NPY family receptor was expressed, they assumed brain tissue. Instead, expression was almost exclusive to the mosquito rectum, a structure Duvall says she did not know existed as a distinct entity until the result came back. The rectal finding stopped looking strange once the mammalian literature caught up. Humans and other mammals have NPY2 receptors in the colon, and non-neuronal excitable cells there are known to synthesize and release neurotransmitters. Work on neuropod and enterochromaffin cells in mammals has become a guide for what Duvall's lab looks for next in the mosquito gut. Removing the experimenter from the room removed a source of bias. Duvall's team built an automated system to deliver host associated cues to mosquitoes around the clock, including at 4am and in darkness, specifically because a human presence, and even which human is present, measurably skews mosquito attraction data. Baseline attractiveness to mosquitoes is real, stable, and not about soap. Referencing work from a former labmate, Duvall described how a person's attractiveness to mosquitoes stays consistent over time regardless of shampoo or soap, which is why her lab has to control carefully for who serves as the human stimulus in an assay. One receptor sits at the intersection of two very different behaviors. The same NPY family Duvall calls her favorite includes a receptor in the female mosquito that detects a male derived signal after mating and suppresses her receptivity to mate again, sometimes for the rest of her life. Disrupting it experimentally can leave females able to mate with multiple males. Disrupting one behavior could interrupt transmission of several diseases at once. Because Aedes aegypti transmits Zika, dengue, and chikungunya through the same host seeking behavior, Duvall argues that turning off attraction to humans at the level of the receptor could block all of these pathogens at their point of transmission, rather than requiring a therapeutic for each one. Episode Timeline - Growing up in rural North Carolina, where the path to science ran through a work study job in a lab - Choosing neuroscience and circadian rhythms as a graduate research focus - Studying pigment dispersing factor signaling in Drosophila clock cells, and a first entry point into GPCRs - An interview that turned into a mosquito postdoc with Leslie Vosshall - Identifying a neuropeptide Y family receptor important for blood feeding regulation - A CRISPR edit that reopened host seeking behavior in blood fed females - What CRISPR based mosquito gene editing looks like in practice, from guide design to the olfactometer assay - Moving to automated, video tracked behavioral assays to remove human bias from the data - Finding the receptor expressed almost exclusively in the mosquito rectum, and its parallel in the human colon - Disrupting host seeking behavior as a way to block transmission of Zika, dengue, and chikungunya - Building a mosquito research facility from scratch, and what day to day lab life looks like - The receptor behind mating suppression in female mosquitoes, and its favorite status in the lab Timestamps were generated using AI for readability. Selected Quotes "This mutant mosquito disrupting a single gene and changing this incredibly strong behavioral drive was something that was almost magical." "It's a neuropeptide receptor, but in fact it seems to be expressed exclusively in the mosquito rectum. A tissue that I did not know existed until we got this result." "There's nothing more satisfying than just sticking your arm in a tube and seeing if you can get them to turn down their attraction to your arm." "In some ways my view of neuroscience and signaling between the brain and the body is relatively narrow. It's really important to have these sensors everywhere in the system." Guest Links - LinkedIn: https://www.linkedin.com/in/laura-duvall-28a03485/ - Google Scholar: https://scholar.google.com/citations?user=Vk3KGSoAAAAJ&hl=en - Lab: https://www.duvalllab.com/ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Brian Shoichet About Dr. Brian Shoichet BSc in Chemistry from MIT, Ph.D. with Tack Kuntz at UCSF; Postdoc with Brian Matthews in protein stability-activity tradeoffs, crystallography; started my independent lab at Northwestern University Medical School (1996) was recruited back to UCSF in 2003. Dr. Brian Shoichet on the web Google Scholar Shoichet Lab Twitter Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Evi Kostenis About Dr. Evi Kostenis "Pharmacist by training - PhD in Pharmacology - Postdoc at the NIH with Dr. Juergen Wess - Postdoc and Group leader in Aventis, now Sanofi, Frankfurt, Germany - Head of in vitro Pharmacology at 7TM Pharma in Denmark; Full professor, department chair and director of the institute for pharmaceutical Biology at the University of Bonn. Research interests: Signaling mechanisms involving GPCRs and heterotrimeric G proteins" Dr. Evi Kostenis on the web University of Bonn ResearchGate LinkedIn Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Alessandro Nicoli shares how he models olfactory GPCRs with AlphaFold, mentors students, and builds science from scratch in a new lab. A fresh look at computational GPCR research. << Back to podcast list Strategic Partner(s) Smells Like GPCR Spirit: Cracking Olfactory Codes with Alessandro Nicoli The Accidental Path to Science Alessandro Nicoli didn’t grow up knowing he’d be a scientist. Like many, his path to GPCR research wasn’t linear—it evolved through academic exploration and mentorship. “I think I don’t have a linear trajectory… the beauty of seeing molecule design and reactions—thinking you can create molecules—was really exciting.” – Alessandro Nicoli He studied pharmaceutical chemistry in Padua, where his fascination with molecular design first took shape. But it wasn’t until meeting an inspiring professor, Prof. Moro, that he truly saw how molecules could go beyond the bench and interact with biology in powerful ways. The Moment Chemistry Met Biology Nicoli’s turning point came when he realized that molecules weren’t static—they could act , bind , and modulate biological targets. “It was not just a molecule—it was a partner that goes to interact with something else… a protein, DNA, RNA. That opened up a new world.” – Alessandro Nicoli That early spark led him to discover the role of medicinal chemistry and, eventually, molecular modeling. For Nicoli, chemistry became more than reactions—it became a bridge to biological insight. Falling for Computational Chemistry The "second academic love" arrived during his master’s thesis, where Nicoli dove into computational chemistry. “I got to know computational chemistry through a project on BCL2 proteins and drug discovery… I was in love with the topic.” – Alessandro Nicoli Working on docking and NMR studies for cancer-related proteins, he discovered the power of simulation in revealing molecular interactions. That experience convinced him to pursue a PhD and deepen his computational skills—eventually leading him to GPCRs. Finding the Right Mentor and Lab A birthday email changed everything. Professor Moro forwarded a PhD opening from Prof. Antonella Di Pizio’s lab in Munich. It felt serendipitous—and it was. “We had a super match… and after a month, I was already in Germany. I was her first PhD student.” – Alessandro Nicoli Starting from scratch in a young lab wasn’t easy, but it created a unique bond between PI and student. Nicoli thrived in this setting—helping shape the lab and its direction, particularly in computational studies of olfactory GPCRs . GPCRs, Receptors of Infinite Variety When asked about his favorite GPCR, Nicoli refused to pick. “Let’s embrace the challenge to study all of them… they’re unique in how they bind ligands, how selective they are.” – Alessandro Nicoli He emphasized that olfactory receptors , while underexplored, present an incredible challenge. With hundreds of subtypes and very few known ligands, the structure–function relationships remain largely mysterious—and incredibly exciting for a computational chemist. AlphaFold: A Turning Point in GPCR Research When Nicoli began his PhD, AlphaFold hadn’t yet revolutionized the field. But once released, it changed everything. “AlphaFold gave us a face to those proteins… now we have 400 models to start with.” – Alessandro Nicoli He explained how AlphaFold’s predictions, surprisingly close to experimental structures, provided a powerful starting point for docking, dynamics, and ligand design—especially for receptors previously “invisible” to structural biology. Modeling the Invisible: Olfactory Receptors Nicoli’s work centers on predicting ligand binding and receptor behavior for olfactory GPCRs. “The main challenge was: how do we get a face for these proteins when we don’t have ligands?” – Alessandro Nicoli He shared a detailed case study of working on a specific odorant receptor (R5VK1), where they leveraged known active/inactive ligands to validate models through iterative refinement , molecular docking , and mutagenesis-guided optimization . The goal? Build predictive models to discover new ligands . Why Molecular Dynamics Matters For Nicoli, molecular dynamics is more than simulation—it’s how we watch biology move . “You simulate over time… see how receptors move in physiological conditions, with water, membranes, ligands.” – Alessandro Nicoli He emphasized that MD allows researchers to observe allosteric changes , mutation effects , and even ligand entry/exit paths , offering dynamic insights that static structures cannot. It’s a critical complement to experimental work. From Researcher to Mentor: Growing Together Outside his research, Nicoli mentors students, manages interns, and even lectures. Balancing this with a PhD isn't easy, but it’s deeply rewarding. “You have people that rely on you… but you grow together, and that’s the most powerful thing.” – Alessandro Nicoli He reflected on learning to delegate—how hard it was initially to hand over tasks—but how vital it is for team science. He now sees mentoring as a way to shape the next generation while evolving himself as a scientist. Advice, Tools, and the Future of GPCR Research Nicoli offered advice to wet-lab scientists curious about computational work: Start with passion. Learn Python. Explore online resources like “Talktorials.” “We’re living in a golden era for computational chemistry… the tools are out there. You just need the motivation to explore.” – Alessandro Nicoli As for what’s next? More structures, better tools, and deeper insights into the elegant, complex world of GPCRs. He sees a future where wet and dry labs converge , and where computational methods are fully integrated into GPCR drug discovery pipelines. Key Takeaway Alessandro Nicoli’s journey is a compelling example of how computational chemistry can unlock new frontiers in GPCR research , especially in complex areas like olfactory receptors. By bridging structural prediction, molecular dynamics, and ligand discovery, his work not only deciphers biological mysteries but also inspires a new generation of scientists to think computationally. About Alessandro Nicoli Alessandro Nicoli is currently a PhD student in the Molecular Modeling group led by Prof. Dr. Antonella Di Pizio at the Leibniz Institute for Food Systems Biology at the Technical University of Munich (Germany). He obtained an MSc degree in Chemistry and Pharmaceutical Technology from the University of Padua (Italy). His training and passion for computational chemistry started in 2019 during his time at the Molecular Modeling Section (MMS) under the supervision of Prof. Stefano Moro, where he worked on integrated Nuclear magnetic resonance (NMR) and computational modeling strategies to target the antiapoptotic BCL-2 protein family, key regulators of cell survival, using small molecules. He then moved to Germany in 2019 to pursue his PhD. His research focuses on a group of 400 transmembrane proteins known as olfactory receptors, which mediate the sense of smell. Beyond the olfactory epithelium, these receptors are expressed in various tissues, where they play important but not yet fully understood roles in various physiological and pathological processes. Despite their relevance, they remain understudied due to the limited knowledge of their ligands and the lack of experimental structures. Alessandro PhD work aims to fill these gaps by leveraging computational structure-based tools and develop specific protocols to accelerate OR ligand discovery and improve our understanding of olfactory function at the molecular level. Alessandro Nicoli on the web Leibniz Institute for Food Systems Biology at the Technical University of Munich Technical University of Munich Google Scholar Pubmed ORCID ResearchGate X Bluesky Github Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Stephen Ferguson The History of the Great Lakes GPCR Retreat with Dr. Stephen Ferguson About Dr. Stephen Ferguson Dr. Stephen Ferguson is a Professor in the Department of Cellular and Molecular Medicine at the University of Ottawa. He did B.Sc. in biology at McGill University and received his Ph.D. under the mentorship of Dr. Brian Collier in the Department of Pharmacology and Therapeutics at McGill University (1994). He did his postdoctoral training with Dr. Marc G. Caron at Duke University (1994-1997), where he and his colleagues investigated the role of G protein-coupled receptor kinases and beta-arrestin in regulating G protein-coupled receptor endocytosis, trafficking, and signaling. He has held four Canada Research Chairs since 2001 and was previously a Heart and Stroke Foundation of Canada MacDonald Scholar (1998-2003) and Heart and Stroke Foundation of Ontario Career Investigator (2003-2016). He was a recipient of Canada's Top 40 under 40 award in 2004 and received Queen Elizabeth II, Diamond Jubilee Medal, in 2012. He has also received both Junior (2001) and Senior (2005) investigator awards from the Pharmacological Society of Canada. Most recently, in 2021, he was elected as a Fellow of the Canadian Academy of Health Science (FCAHS). His research career has focused on the investigation of the regulation of G protein-coupled receptors signaling mechanisms in health and disease. He currently holds multiple research grants from the Canadian Institutes of Health Research (CIHR) for his research investigating the role of metabotropic glutamate receptor signaling in Huntington’s and Alzheimer’s disease. Dr. Stephen Ferguson on the web Carlton University Canada Research Chairs Twitter ResearchGate LinkedIn Dr. GPCR Ecosystem Great Lakes GPCR Retreat on the web 21st Great Lakes GPCR Retreat More about previous GPCR Retreat meetings Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Juan José Fung About Dr. Juan José Fung Dr. Juan José Fung is a Principal Scientist at GPCR Therapeutics, Inc , a drug discovery company focused on targeting GPCR heteromers in cancer, headquartered in Seoul, Korea, with an R&D facility in the SF Bay Area. Dr. Fung received his Ph.D. from the Stanford University School of Medicine under the mentorship of Dr. Brian Kobilka , studying the dimerization of GPCRs. Dr. Fung continued his Postdoctoral training in Dr. Kobilka’s lab contributing to the elucidation of high-resolution structures of various GPCRs. Dr. Fung has spent significant time in the industry studying membrane proteins, antibodies, and HTS methods for drug discovery. His current work is mainly focused on screening and assay development to bridge the gap between in vitro and in vivo GPCR pharmacology. Dr. Juan José Fung on the web LinkedIn GPCR Therapeutics Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Anything BUT GPCRs with Dr. Mikel Garcia-Marcos About Dr. Mikel Garcia-Marcos "I was trained as a biochemist and molecular biologist during my Ph.D (2005) in Spain and Belgium, and subsequently as a cell biologist during my postdoc (2006-2011) with Dr. Marilyn Farquhar (UC, San Diego), a pioneer of modern Cell Biology. All my formal training was in the area of signal transduction, and I continued to work on this area since I established my own laboratory in the Department of Biochemistry at Boston University in 2012. My research aims to understand the mechanisms and consequences cell communication via heterotrimeric G-proteins (Gαβγ) because they represent major intracellular hubs of signaling with very direct biomedical relevance. To achieve this goal, we use a wide range of established approaches (biochemistry, cell biology, genetics) and experimental systems (purified proteins, cultured cells, model organisms) in combination with the development of novel tools (biosensors, chemogenetics, optogenetics). Our ongoing efforts have direct implications in cancer, embryonic development defects, and neurological disorders." AI Summary In the podcast episode "Anything but GPCRs" featuring Dr. Mikel Garcia-Marcos, the host Yamina explores Dr. Garcia-Marcos's academic journey, which spans training in Spain, Belgium, and a postdoctoral fellowship at UC San Diego, where he navigated a career focused on G protein-coupled receptors (GPCRs) while aiming to maintain broad scientific interests. Dr. Garcia-Marcos shares insights on transitioning from postdoctoral research to leading his own lab, addressing the challenges of applying for academic positions and the importance of networking, adaptability, and mentorship in fostering a collaborative research environment. The conversation further delves into the dynamics of managing a diverse team, emphasizing the role of personality assessments in enhancing team cohesion and performance. Dr. Garcia-Markos reflects on milestones in his research journey, reinforcing the passion that drives scientists in the GPCR field, and engages listeners to connect with the podcast for a richer community experience. Dr. Mikel Garcia-Marcos on the web Boston University LinkedIn Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Khaled Abdelrahman About Dr. Khaled Abdelrahman Dr. Khaled Abdelrahman graduated in 2006 with a BSc in Pharmaceutical Sciences from Alexandria University (Egypt) followed by MSc in Pharmacology in the same university that was conferred in 2009. He joined the laboratory of Dr. William Cole at the University of Calgary in 2010 for his Ph.D. where he studied the molecular basis underlying altered cerebrovascular function and blood flow in type 2 diabetes. In 2015, He joined Dr. Stephen Ferguson’s laboratory in the Departments of Cellular & Molecular Medicine and Neuroscience at the University of Ottawa as a Postdoctoral Fellow to explore novel G protein-coupled receptor (GPCR) candidates that can be targeted pharmacologically to slow neurodegeneration. He has been also studying what aspects of GPCR signaling are regulated in a sex-selective manner and how this can influence drug discovery in the area of neurodegenerative diseases. He is also a Registered Pharmacist in Canada and held two of the most prestigious Clinician Postdoctoral Fellowships offered by Alberta Innovates and Canadian Institutes of Health Research. He received the Canadian Society of Pharmacology and Therapeutics Postdoctoral and Publication awards along with many Young Scientist Awards from the American Society for Pharmacology and Experimental Therapeutics. Dr. Khaled Abdelrahman on the web Twitter PubMed Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 Webinars 📅 Tuesday, March 3, 2026 at 10:00:00 AM EST 🤝 Webinar in collaboration with: Celtarys Research Fluorescent Probes for GLP-1R and GIPR Imaging: From Cell Assays to In Vivo Systems Fluorescent tools for imaging endogenous incretin receptors across biological systems Interrogating Incretin Receptor Biology Across Biological Complexity GLP-1 and GIP receptors have emerged as central targets in metabolic medicine, yet their precise localization, nanodomain organization, and functional engagement within complex biological systems remain incompletely understood. Fluorescent chemical probes offer one of the most direct approaches for investigating receptor distribution and dynamics in native contexts — without relying on receptor overexpression or genetic modification. This webinar introduces two families of advanced fluorescent probes developed specifically for working with endogenous GLP-1R and GIPR across a range of biological complexity. Attendees will gain a technical understanding of probe design, selectivity, and validated applications — as well as practical guidance on handling, reconstitution, dilution, and storage to support immediate laboratory deployment. LUXendin Family Red and far-red fluorescent GLP-1R antagonists derived from Exendin4(9–39). Enable high-specificity labeling of endogenous GLP-1R in live and fixed cells, pancreatic islets, and whole-organ preparations — without triggering receptor activation. Available across multiple spectral ranges for confocal, super-resolution, and intravital imaging. daLUXendin Family Fluorescent dual agonists for both GLP-1R and GIPR (daLUXendin544+ and daLUXendin660+), structurally related to tirzepatide. Enable simultaneous visualization of endogenous receptor localization and nanodomain organization in pancreatic islet cells and neural sites of action in vivo. Speakers Dr. Johannes Broichhagen Group Leader Leibniz Research Institute for Molecular Pharmacology (FMP), Berlin Dr. Broichhagen trained in chemistry at the University of Erlangen-Nuremberg, completed his doctorate at LMU Munich in 2014, and undertook postdoctoral work at EPFL (Switzerland) and the Max Planck Institute for Medical Research (Heidelberg). Since 2020, he leads an independent research group at the FMP Berlin. His group focuses on the development of chemical tools — including fluorescent ligands and photopharmacological compounds — to investigate GPCR biology with spatial and temporal precision. He is a principal architect of the LUXendin and daLUXendin probe families. Dr. David Hodson Robert Turner Professor of Diabetic Medicine Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford Dr. Hodson is a veterinary surgeon by training who pursued postdoctoral studies at the CNRS in Montpellier before establishing his independent laboratory at Imperial College London as a Diabetes UK RD Lawrence Fellow. He previously served as Professor of Cellular Metabolism and Institute Deputy Director at the University of Birmingham. His research group develops and applies novel technologies to investigate GLP-1 and GIP receptors — two class B GPCRs central to glucose homeostasis, food intake regulation, and inflammation — within complex tissue environments including the pancreas and brain. His work carries direct translational relevance to diabetes and obesity therapeutics. Organizers Celtarys Research Celtarys develops and commercializes fluorescent chemical tools and related screening services that enable fluorescence-based methods across drug discovery. The company's portfolio is built around high-affinity, selective fluorescent ligands for GPCRs, supporting researchers working at the interface of chemical biology and pharmacology. Broad GPCR fluorescent ligand portfolio across multiple receptor families Fluorescence Polarization, HTRF, and High-Content Screening formats Fluorescence microscopy and flow cytometry applications Screening services using proprietary probes in living cells Custom chemical development for probe and ligand creation Dr. GPCR Dr. GPCR is a membership-based nonprofit ecosystem dedicated to advancing GPCR-targeted drug discovery. It provides curated industry intelligence, expert-led masterclasses, and structured engagement opportunities for scientists and biotech leaders working across pharmacology, translational research, and therapeutic development. Curated intelligence on GPCR drug discovery trends and developments Expert-led webinars and masterclasses with leading researchers Structured networking for scientists and biotech professionals Nonprofit model — community-first, member-driven Free membership tier available Previous Webinar Next Webinar Don’t Miss the Next Live Session Dr. GPCR membership gives you access to all upcoming live, interactive webinars. Free. Takes less than a minute to join. Cancel anytime. Sign Up for Free

Annette Gilchrist on why native cell systems change GPCR screening, constitutive beta-arrestin activity at FFA2, and the pharmacogenomics gap in drug discovery. << Back to podcast list Strategic Partner(s) Annette Gilchrist: Native Cell Systems, Biased Agonism, and the Pharmacogenomics Gap Biased agonism promised a cleaner path to better drugs - compounds that activate the beneficial arm of a receptor while leaving the harmful one alone. In practice, the picture is far more complicated. Whether a 20% reduction in beta-arrestin coupling matters therapeutically depends on the cell type, the complement of intracellular effectors present, and the receptor's own baseline activity in that tissue. These are questions you cannot answer in a HEK cell overexpressing a receptor it was never meant to see. Annette Gilchrist has built her research program around that premise. Working on chemokine receptor CCR1 in multiple myeloma, free fatty acid receptor FFA2 in type 2 diabetes, and muscarinic receptors, her lab screens in disease-relevant cell lines and looks early for signaling bias - not as a theoretical exercise, but as a practical filter on what a compound might actually do in a patient. That discipline led to a finding her field had not documented before: constitutive beta-arrestin activity at a wild-type FFA2 receptor, suppressible by an inverse agonist that then redirects signaling toward GQ coupling. For Gilchrist, the result was not a surprise so much as a confirmation - if you look in the right system, receptors show you things overexpression models never could. ABOUT THE GUEST Annette Gilchrist is Associate Professor of Pharmaceutical Sciences at Midwestern University, where her research focuses on GPCR signaling in disease-relevant contexts. Her lab studies chemokine receptor CCR1 in multiple myeloma and cancer-to-bone metastasis, free fatty acid receptor FFA2 in type 2 diabetes, and muscarinic M2 and M3 receptors, consistently prioritizing native and disease-proximal cell systems for screening. Before returning to academia, she co-founded two GPCR-focused biotechs with Heidi Hamm - CUE Biotech and Caden Biosciences - developing G-protein C-terminal mini-gene peptide tools that became widely adopted across the field. She also brings early industry experience from Pfizer, where her first sustained encounter with pharmacology as a discipline shaped how she has thought about the relationship between target validation and drug development ever since. SCIENTIFIC THEMES OF THE CONVERSATION The native cell argument - why overexpression models produce systematically misleading screening data and what disease-relevant cell lines reveal instead The practical limits of biased agonism - cell-type context, effector availability, and why the G-protein vs. beta-arrestin framing rarely holds at the clinical level Constitutive beta-arrestin activity and inverse agonism - a first-in-kind finding at wild-type FFA2 and its implications for biased ligand campaign design GPCR pharmacogenomics - natural receptor variation, interpatient drug response differences, and a largely unexplored opportunity in existing drug pipelines Antibody therapeutics for GPCRs - the pipeline case, the approval rate argument, and why orphan receptor targeting may not require knowing the endogenous ligand Receptor dimerization - BRET biosensors, what we still do not know about physiological relevance, and why the tools are finally beginning to close the gap KEY INSIGHTS FROM THE CONVERSATION The cell you screen in determines the biology you can find Running a GPCR screen in a HEK cell overexpression model removes the intracellular proteins a receptor actually encounters in disease tissue - effectors like Go or Gz that are critical in neuronal signaling, for example, and simply absent in standard lines. Gilchrist has argued for disease-relevant cell systems for over 15 years, and her lab's discovery of constitutive beta-arrestin activity at FFA2 is a direct product of that discipline - a result that would have been invisible in a standard overexpression model. Biased agonism is context-dependent, not receptor-intrinsic The field has treated biased agonism largely as a property of a compound and a receptor. Gilchrist's argument is that it is also a property of the cell. The same compound may produce a functionally meaningful shift in one cell type and a negligible one in another, depending on the G-protein isoforms present, the receptor conformation in that membrane environment, and what other proteins are competing for the same intracellular space. How much bias is enough is not a pharmacological question with a single answer. An inverse agonist where none had been reported - constitutive beta-arrestin coupling at FFA2 Gilchrist's lab entered the FFA2 project looking for GQ-biased agonists to drive insulin release. What they found instead was that FFA2 appears to be constitutively coupled to beta-arrestin in the relevant cell system - and that an inverse agonist against that constitutive activity effectively redirects the receptor toward GQ coupling. It was a result that had been documented in a mutant vasopressin receptor but never in a normal wild-type receptor. The aha moment was not the result itself but recognizing what it meant for how you could design the campaign. Pharmacogenomic variation in GPCRs may already be shaping clinical drug response - unacknowledged A paper by Hauser mapped pharmacogenomic variation across the GPCR-ome and showed, among other findings, that many of the GPCRs carrying the highest mutation loads are hormone receptors - FSH, LH, and others implicated in fertility. Patients taking drugs that target GPCRs with natural population-level variants are almost certainly responding differently based on their receptor genetics. Almost no company with an approved GPCR-targeting drug has gone back to look at what common receptor variants do to their compound. Gilchrist believes they should. The mini-gene origin: reading one paper, seeing the missing experiment While a postdoc in Heidi Hamm's lab, Gilchrist read a paper describing how BARK C-terminal peptides had been inserted into a plasmid as tools. The question that followed was immediate: why hadn't anyone done the same with G-protein C-termini? The peptides she developed - 11 amino acids rather than 55, which created their own detection challenges - became widely used across the field for measuring receptor-G-protein interactions and screening for allosteric modulators. The insight was not a long deliberation. It was a single reading of someone else's work and a recognition that an obvious experiment had not yet been done. Antibody therapeutics for GPCRs: the pipeline argument Biologics have a substantially higher success rate than small molecules moving through the drug development pipeline. GPCRs are well-validated targets with known physiological relevance. The combination of those two facts, Gilchrist argues, makes antibody-based GPCR therapeutics an underexplored area - particularly for orphan GPCRs, where compounds are already being developed against receptors whose endogenous ligands remain unknown. The precedent of drugging a receptor without knowing what activates it naturally, and getting therapeutic results, suggests the field does not always need the full biology before it can act on the pharmacology. The first screen: looking for antagonists, finding agonists instead The principle that Gilchrist now teaches - follow the unexpected result, ask why it happened, do not repeat it away - came from her own first encounter with exactly that situation. Running a small-molecule screen in Heidi Hamm's lab, looking for compounds that would block G-protein binding, she found agonists: compounds that made the G-protein bind better, some of which trapped the receptor in a state where it could not signal further. It was not the experiment she had designed. The years of research that followed came directly from not dismissing it. EPISODE TIMELINE Timestamps are AI-generated from the transcript and may not reflect the final edited episode. 00:00 Introduction 02:18 Career trajectory - from medical school intent to Pfizer, PhD in immunology, and an accidental entry into GPCR biology 07:25 Entering GPCR research through Heidi Hamm's lab - and why the committee said G proteins had already won their Nobel Prize 12:39 Co-founding CUE Biotech and Caden Biosciences - allosteric modulator screens and G-protein C-terminal peptide tools 17:17 Current receptors: CCR1, FFA2, and muscarinic M2 and M3 19:28 CCR1 in multiple myeloma - osteoclast/osteoblast imbalance and the cancer-to-bone metastasis problem 23:01 Why native cell lines change what a screen can detect 27:53 The limits of biased agonism - effector context, cell-type dependence, and allosteric complexity 32:08 GPCR pharmacogenomics - variant receptors, the Hauser paper, and what industry has not yet done with existing drugs 39:43 BRET biosensors, receptor dimerization, and what remains unresolved about physiological relevance 42:00 Antibody therapeutics for GPCRs and the case for orphan receptor targeting 48:27 Two aha moments: the G-protein mini-gene origin and finding an inverse agonist where none had been reported SELECTED QUOTES "Being a scientist is like being an artist. You do it because you can't imagine your life doing anything else. I do science because I love science. I love asking a question - I get to find an answer that nobody else knows, potentially." "I had no idea that I would find agonists, biased agonists, as well as antagonists the first time I did my screen. When you have a finding that is completely unexpected, you follow it. You ask the question: why did that happen? Instead of just trying it again." "How much is enough in terms of turning it down? Is a 20% reduction of beta-arrestin signaling enough? I think it is probably cell-dependent. So much of the interaction depends on the conformation of the receptor in that particular cell." "As much as it's been wonderful to get crystal structures and use molecular dynamics, there are still so many questions that we have no idea what the answer is. I guess that's one of the best things about GPCRs - there's always something to look at." About this episode Originally, Annette wanted to be a medical doctor but as luck has it, she didn’t get into medical school when she first applied. Instead, she discovered research and started her Ph.D. the day she should have started medical school. Dr. Gilchrist completed her Ph.D. in Biomedical Sciences / Immunology at the University of Connecticut and went on to become a postdoctoral fellow at UIC (University of Illinois at Chicago). Annette worked in industry, academia and her entrepreneurial side led her to three companies, Cue Biotech , Caden Biosciences , and MyGenomeRx in addition to being a consultant for over a decade. Dr. Gilchrist is also an associate professor at the Department of Pharmaceutical Sciences. Join me and learn more about Annette’s career, our common love for chemokines, and how you can use your training as a scientist in so many different ways. Dr. Annette Gilchrist on the web LinkedIn Midwestern University Google Scholar Pubmed Twitter Research Gate Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Amynah Pradhan on why mu opioids worsen migraine, why delta agonists may relieve it, and how chronic disease states rewrite drug discovery. << Back to podcast list Strategic Partner(s) Amynah Pradhan: The Delta Opioid Receptor and the Migraine Paradox Chronic migraine sits at a peculiar crossroads in opioid pharmacology: sustained mu opioid receptor activation is a well-documented driver of medication-overuse headache, while preclinical evidence points to delta opioid receptor agonism as a candidate to relieve the same disorder. Dr. Amynah Pradhan's lab at the University of Illinois at Chicago has spent years pulling apart that asymmetry — combining mouse models of chronic migraine, cortical spreading depression, and opioid-induced hyperalgesia with peptidomic screens and conditional genetics to ask where the two receptors diverge anatomically, pharmacologically, and in the chronic disease state. The work sits inside a larger argument Dr. Pradhan returns to often: that organisms in chronic pain are fundamentally different biological systems than naïve ones, and that drug discovery fails when it pretends otherwise. For her, this line of work is also personal — the delta opioid receptor has been her scientific focus for nearly two decades, through failed clinical trials in depression and pain, and migraine may finally be where it finds a clinical home. About the Guest Dr. Amynah Pradhan is Associate Professor of Psychiatry at the University of Illinois at Chicago, where her lab studies opioid receptor biology in the context of headache disorders, chronic pain, and their comorbid emotional states. She trained in pharmacology at McGill University with Paul Clarke and completed postdoctoral work at AstraZeneca, with Brigitte Kieffer in Strasbourg, and with Chris Evans at UCLA. Her research integrates behavioral pharmacology, ligand-directed signaling, and mouse models of migraine, and has become central to the small community of basic pharmacologists working inside the headache field. Scientific Themes of the Conversation The mu/delta asymmetry in migraine — why two receptors in the same family produce opposite clinical outcomes Chronic disease states as fundamentally altered biological systems — and what that means for drug discovery Ligand-directed signaling and receptor trafficking — how internalization shapes tolerance and adverse effects The emotional circuitry of chronic pain — and the kappa opioid / dynorphin link The unfinished GPCR frontier — PACAP, CGRP, and the persistent antibody problem Career mobility through collaboration — how a headache neurologist redirected two decades of work Key Insights from the Conversation The yin-yang that organizes the lab. Mu opioid agonists, in chronic use, exacerbate migraine and drive medication-overuse headache. Delta opioid agonists appear to relieve the same symptoms — pain, negative affect, and aura-related signs in preclinical models. Dr. Pradhan treats the contrast not as a side story but as the organizing question of her work. Chronic states are not scaled-up acute states. One of Dr. Pradhan's recurring arguments is that the organism in a chronic disease state is fundamentally altered, and that drug candidates fail in clinical trials partly because they are validated in naïve animals that do not resemble the patients they will eventually treat. Internalization is a design choice, not a side effect. Earlier work in her career showed that high-internalizing delta agonists drive receptor downregulation and tolerance, while low-internalizing agonists uncouple the receptor from ion channels without losing it. The ideal delta agonist, by her account, would be non-internalizing, brain-penetrant, long-half-life, and directed at forebrain circuits where emotional salience of pain lives. Delta agonists may finally have a disease. After failed trials in depression and pain, Dr. Pradhan argues that migraine — with its emotional comorbidity, its anatomical overlap with delta receptor expression, and its distinctive pain mechanisms — may be the clinical home the compound class has been looking for. The conviction is quiet but deeply held. The antibody problem is keeping a field from basic answers. Her "bugaboo": we still do not know reliably where many GPCRs live — which cell type, which compartment, surface versus intracellular — because antibodies for the family are widely unreliable. For a pharmacologist, the resolution problem sits upstream of every other question. A single collaboration can redirect a career. Her move from pure opioid pharmacology into migraine came from sharing a building with neurologist Andrew Charles at UCLA. She treats this as a generalizable lesson for junior scientists: openness to collaboration is not decorative — it is how fields get rewired. The invisible labor of being the only one in the room. Toward the end of the conversation, Dr. Pradhan turns to the structural weight carried by women and scientists of color in academia — the cumulative load of committee service, mentorship, and representation — and argues that real support requires institutions to account for it, not just request it. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction 01:13 From McGill to migraine — a path through four labs 04:19 Why mu worsens migraine and delta relieves it 09:27 What chronic dosing does to the receptor — tolerance, internalization, downregulation 14:17 Designing the delta agonist she wants 17:30 The emotional circuitry of chronic pain — and the kappa link 22:22 CGRP, PACAP, and why GPCR drug discovery is not out of runway 28:54 Biased ligands after the hype cooled 34:08 How you measure migraine in a mouse 40:44 Three aha moments — and why delta agonists may finally have a home 43:28 The hidden cost of being the only one in the room 57:05 What the pandemic did to a mouse colony Selected Quotes "The delta opioid receptor is my baby. I've been working on it for almost 20 years under lots of different contexts." "The organism is fundamentally altered in a chronic disease state. They're not in the same state as they were if they were naïve. Patients didn't come to the doctor to look for drugs because they were feeling fine." "Every person I know who studies G-protein coupled receptors will tell you — the antibodies suck. We're still arguing about where the receptor is. What cell type it's on. Is it on the cell surface? Is it inside the cell? The fact that we can't say that is kind of crazy to me." "Maybe the disease state where delta ligands would really be effective would be in headache disorders — in migraines specifically. Maybe this is where it all comes together." About this episode In this episode of the Dr. GPCR podcast , we meet with Dr. Amynah Pradhan. She is an Associate Professor of Psychiatry at the University of Illinois at Chicago. Amynah did her undergrad research measuring IP3 in airway smooth muscle cells and completed a Ph.D. at McGill University in Canada with Dr. Paul Clarck , where she studied opioid receptors. Her next career step took her to AstraZeneca as a postdoctoral trainee, where she studied animal models of pain and sensory neuron sensitive-receptor. She then returned to academia and worked on opioids as a postdoctoral trainee with Dr. Brigitte Kieffer , where she studied ligand-directed signaling at the delta-opioid receptor. Her career path-defining moment came from a third postdoctoral experience with Dr. Chris Evans at UCLA. Amynah studied how arrestins regulate ligand-directed signaling at delta-opioid receptors, and it is their collaboration with a headache physician-scientist Dr. Andrew Charles that who specialized in animal models of migraine and delta-opioid receptors as a therapeutic target to treat headache. Dr. Amynah Pradhan on the web Lab page LinkedIn Twitter Google Scholar PubMed Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Self-Learning, Collaboration, and Delegation in Science with Dr. Badr Sokrat About Dr. Badr Sokrat " After completing my undergraduate studies with an internship in the laboratory of Dr. Christian Baron studying bacterial secretion systems, I joined the molecular pharmacology laboratory of Dr. Michel Bouvier at the University of Montreal. There, I completed a PhD in biochemistry exploring the non-canonical functions and possible novel mechanisms of regulation of β-arrestin following GPCR activation. Among other projects, I studied the role of β-arrestin in G protein trafficking, the impact of GPCR ubiquitination on signaling and β-arrestin functions, and the characterization of novel β-arrestin interactors. At the end of 2023, I joined the research group of Dr. Nigel Bunnett at the NYU Pain Research Center as a postdoctoral researcher. My current research focuses on investigating GPCR signaling and trafficking in the context of inflammation and chronic pain. I am particularly interested in spatial signaling bias or how GPCRs can redistribute to different subcellular compartments to trigger distinct signaling events. " Dr. Badr Sokrat on the web PubMed ResearchGate LinkedIn Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick Recap Yamina and Badr discussed their backgrounds in science, their experiences in education, and the challenges of competition and mental health in their home province of Quebec. They also discussed Badr's career trajectory, the importance of self-learning, collaboration, and delegation in scientific research, and the need for a well-organized lab manager in their global scientific team. Lastly, they highlighted the challenges scientists face in academia and industry, the importance of projection and careful communication, and the potential for future collaboration. Next Steps Badr will continue focusing his research on GPCRs involved in pain and inflammation during his postdoc at NYU. Yamina and Badr will create a virtual genealogical tree mapping the connections between researchers in the GPCR field. Yamina will continue to develop and manage the Dr. GPCR University podcast, focusing on collaboration and learning opportunities for the GPCR community. Yamina will balance her scientific work with personal interests and activities to maintain a healthy work-life balance. Summary Podcast Recording and Science Backgrounds Yamina and Badr discussed recording their podcast with Samary Eye, who made a humorous error in transcribing "Edmond" as "agendie". They then shared their backgrounds and interests in science, with Badr recounting his journey from struggling with math in an engineering physics degree to excelling in biology and obtaining a Master’s degree in biochemistry. Badr worked in various science labs, including Dr. Christian Badr’s and Dr. Philip Woozab’s, focusing on bacterial secretion systems, GPCRs, and bioinformatics. Yamina, who also attended the University of Montreal, confirmed her interest in science and mentioned their shared passion for the subject. Education, Competition, and Mental Health Discussion Badr and Yamina shared their experiences about their education, with Yamina sharing her struggles during her first trimester in college and her eventual success due to the support of a theater group and a good teacher. They both discussed the intense competition in their home province, Quebec, and its impact on students' mental health and university admission prospects. They also talked about the negative aspects of this competition, such as students putting others down, and how it can be toxic. Lastly, Badr shared his transition into the field of GPCRs.. Badr recounted Badr's Journey, Multiplexing Assays, and Collaboration Badr shared his learning process and early tasks at Michelle’s lab, which involved creating stable cell lines and identifying potential protein interactions. He described a significant moment when he confirmed a previously uncertain interaction, underscoring the importance of confidence and motivation in scientific discoveries. Yamina emphasized the potential of multiplexing assays in expanding the scope of scientific exploration and finding new protein interactions. They also discussed the concept of serendipity in scientific research, illustrating with examples of Kathleen Curran and her father. Lastly, they concurred on the collaborative nature of the scientific community, where scientists build upon each other's work. Badr's Postdoc Plans and GPCR Research Yamina and Badr discussed Badr’s career trajectory and his decision to pursue a postdoc abroad after his PhD. Badr shared his passion for GPCR signalling and regulation, specifically in the context of pain and inflammation, and how his PhD research on non-canonical GPCR roles laid the foundation for his postdoc work. He also explained his strategy for finding a suitable postdoc lab, which involved reaching out to labs whose recent research aligned with his interests. Lastly, Badr emphasized the importance of choosing a city one would like to live in for several years when deciding on a postdoc position. Badr’s Journey to Overcoming Confidence Fluctuations Badr shared his journey of overcoming fluctuating confidence levels during his PhD journey, emphasizing the importance of viewing failures as valuable learning opportunities. He highlighted that he had to regain his confidence after a period of three failed experiments. Yamina expressed interest in understanding how Badr’s experiences influenced his current role, and Badr stressed the need for individuals to develop challenges outside of their work environment to foster greater confidence. Additionally, they both agreed on the importance of mentorship in building confidence, with Yamina sharing her positive experience of being advised by her supervisor, Nikolaos. Self-Learning, Collaboration, and Delegation in Science Badr and Yamina discussed the importance of self-learning and scientific confidence in managing projects and conducting experiments. They highlighted the significance of collaboration and delegation in scientific research, noting that knowing when to ask for help and when to delegate tasks can lead to more efficient and successful results. Yamina shared her experiences of starting a project independently and then delegating tasks, while Badr shared his plans for his current project, which involved learning certain techniques himself and delegating others to colleagues. They both agreed on the value of these strategies. Yamina’s Podcast Journey and Career Advice Yamina discussed how her podcast on chemokine ligands led to new collaborations and published work. She emphasized preparation and understanding guests’ backgrounds for engaging interviews. Yamina shared her experiences at Rockefeller, where she studied chemical receptors. She aims for Dr. GPCR to serve as a global hub for the GPCR community. Badr expressed interest in broadening his skills beyond the lab, such as project management and effective communication. Yamina advised him to consider career options after his postdoc and adapt to different systems. She highlighted the importance of learning behind-the-scenes skills and staying informed through resources like GPCR news. Improving Scientific Communication and Support Yamina and Badr discussed the need for a well-organized lab manager to facilitate communication within their global scientific team and ensure scientists could focus on their research. They identified the challenges scientists, particularly students and researchers, face, such as imposter syndrome, constant pressure from administrative tasks, and difficulties in maintaining a work-life balance. Yamina and Badr agreed on the importance of individuals struggling with imposter syndrome learning to set aside their fears and doubts to move forward. They also highlighted the benefits of maintaining a supportive network and engaging in non-lab activities for mental processing and relaxation. Academia and Industry Strategies Discussed Yamina and Badr discussed the challenges and strategies of a scientist in academia and industry. Yamina highlighted the need to project a certain presence and balance one’s actions against others in the field. She also mentioned the importance of careful communication, especially when working with a boss who has a different approach. Badr agreed to reach out for a future collaboration, and they discussed the possibility of meeting in Boston. Yamina committed to sending her contact details to Badr. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Arthur Christopoulos About Dr. Arthur Christopoulos " Arthur Christopoulos is the Professor of Analytical Pharmacology and the Dean of the Faculty of Pharmacy & Pharmaceutical Sciences, Monash University, Australia. His research focuses on novel paradigms of drug action at GPCRs, particularly allosteric modulation and biased agonism, and incorporates computational and mathematical modelling, structural and chemical biology, molecular and cellular pharmacology, medicinal chemistry, and preclinical models of behaviour and disease. His work has been applied to studies encompassing neurological and psychiatric disorders, cardiovascular disease, obesity, diabetes, chronic pain and addiction. He has received substantial, long-term support from international and national competitive, charitable and commercial sources, as well as being academic co-founder of three GPCR-focussed biotechnology companies. Professor Christopoulos has over 360 publications, including in leading international journals such as Nature,Science and Cell, and has delivered over 180 invited presentations. He has served on the Editorial Board of 8 international journals and was a Councillor of the International Union of Basic and Clinical Pharmacology (IUPHAR). He has also been the recipient of multiple awards, including the John J. Abel Award and the Goodman and Gilman Award from the American Society for Pharmacology and Experimental Therapeutics; the Rand Medal from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists; the British Pharmacological Society’s Gaddum Memorial Award; the IUPHAR Sir James Black Analytical Pharmacology Lecturer; the GSK Award for Research Excellence and a Doctor of Laws (Honoris Causa) from the University of Athens. Since 2014, Clarivate Analytics have annually named him a Highly Cited Researcher in ‘Pharmacology & Toxicology’, and in 2021 also named him a Highly Cited Researcher in the additional category of ‘Biology & Biochemistry’. In 2017, he was elected a Fellow of the Australian Academy of Health and Medical Sciences, in 2018 as a Fellow of the British Pharmacological Society, and in 2021 he was elected a Fellow of the Australian Academy of Science for his seminal contributions to drug discovery. In 2023, he was elected a Fellow of the Pharmaceutical Society of Australia. " Dr. Arthur Christopoulos on the web Monash University Wikipedia Google Scholar LinkedIn Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina and Arthur from Monash University discussed Arthur's career journey, the importance of hard work, failure, and differentiation in academic and personal lives, and the value of international conferences. They also explored the significance of translating fundamental discoveries into clinical applications, the potential of new drugs, and the unique challenges within universities. Additionally, they discussed the importance of hiring based on differentiation, impact, and interest, the need for workforce development, and the potential of involving junior scientists and postdocs in their podcast. Lastly, they touched upon the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and making pre-lesson materials available to students. Next steps - Yamina will share notes about PRISM and presentability with Arthur. - Arthur will share the story of PRISM's development and its impact on the field with Yamina. - Yamina will send an invite for a follow-up meeting with Arthur next Saturday at 9 PM. - Arthur and Yamina will prepare for the next meeting, focusing on the concept of biased agonism and discussing Dr. GPCR and the charity status. - Yamina will attempt to book Denise for a future podcast episode. Summary Arthur's Career Journey and Transition to Dean Yamina introduced Arthur to her team and discussed the use of a particular tool for meeting summaries. Arthur shared his career journey from pharmacy to becoming a professor, highlighting the influence of his mentors and the importance of his postdoctoral experience. They discussed the value of hard work, failure, and the significance of differentiation in their personal and academic lives. Towards the end, they focused on Arthur's transition to become Dean and his decision to move from Australia to the United States for a postdoctoral position. Postdoctoral Position, Scientific Dynamics, and New Drug Targets Arthur shared his decision to undertake a postdoctoral position with Nigel Bird's lab in the UK and his experiences of meeting influential figures during his time in the US. He and Yamina discussed the importance of preserving original work, the value of international conferences, and the dynamics between junior and senior scientists in a research environment. They also shared their admiration for the work of a mutual friend and discussed the history of muscarinic receptors, specifically focusing on the role of a compound that Arthur received from Fred. Lastly, they discussed the progress of new drugs targeting specific receptors for various diseases, with Arthur sharing insights on Eli Lilly's compound, Xanomeline, and the potential of M4 PAM for psychosis. Collaborative Research and Translational Approach Arthur and Yamina from Monash University discussed their collaborative approach to scientific research, emphasizing the benefits of combining their complementary skills and interests. They shared their unconventional approaches to research, including the creation of a critical mass of GPCR researchers in Australia and the initiation of a successful series of conferences. They also discussed the relocation of some university labs to facilitate collaboration and overcome the siloed department structure. Additionally, they explored the unique culture and structure of their Institute, highlighting its translational approach to research and its capacity to translate research into therapeutic commercialization. Lastly, Arthur shared three significant moments that shaped his career, including the evolution and impact of analytical pharmacology, particularly highlighting the role of Prism, a data analysis tool. Podcast Format, Team Culture, and Science Yamina and Arthur concluded their discussion and decided to take a short break. They talked about the format and length of their podcast, their professional interests, and their recent successful bid to bring Moderna to their university. They also explored the idea of starting a similar talk show format to 'Between Two Ferns', the importance of maintaining team culture, and the potential health issues among well-known scientists. Lastly, they discussed the growth and development of the Monash Institute of Pharmaceutical Sciences, the importance of knowing when to let go in scientific experiments, and the idea of a panel for building and incubating companies. Arthur's Pandemic Journey and Global Challenges Yamina and Arthur discussed Arthur's experiences during the Covid-19 pandemic, his journey as a research fellow in Australia, and his transition to the role of Dean. Arthur shared his insights into the unique grant funding system in Australia, the importance of impact in research, and the challenges of balancing administrative responsibilities with scientific pursuits. He also reflected on his personal health struggles, the growth of his university, and the faculty's successful response to the Covid crisis. The conversation also touched upon Arthur's career decisions, his scientific achievements, and the importance of learning from mistakes and self-confidence. Lastly, they discussed the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and having pre-lesson materials available to students. Translating Discovery Into Clinical Application Arthur and Yamina discussed the importance of translating fundamental discoveries into clinical applications in their research, highlighting the unique opportunities presented by their location and partnerships with other institutions. They stressed the necessity of making their research goals clearer, avoiding replication, and adopting a more assertive approach in grant applications. They also emphasized the significance of fundamental discoveries, the role of biotech, and the need for efficiency and process development in university systems. The conversation highlighted ongoing challenges within universities, including resistance to change and the need to communicate expectations and protect established cultures. Hiring Process, Collaboration, and Education-Focused Initiatives Arthur emphasized the importance of differentiation, impact, and interest in their hiring process and fostering a culture of collaboration. He shared his vision of breaking down barriers and promoting education-focused initiatives, encouraging his team to be innovative and apply their skills to education. Yamina expressed a desire to learn from successful leaders and the importance of recognizing talent and matching it with the needs of a particular project. They also discussed the disruption within the pharmaceutical sector, the importance of workforce development, and the need for maintaining a healthy work-life balance. Lastly, they deliberated on involving junior scientists and postdocs in their podcast and the possibility of writing a book about their experiences in academia. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Jacob Lee and Jin Cho, co-founders of GeneMode, on the ten billion dollars American labs waste every year — and why rebuilding research software from scratch is the most direct path to faster cures. << Back to podcast list Strategic Partner(s) Jacob Lee and Jin Cho: Rebuilding the Software Layer Under Modern Research Most scientific research still runs on infrastructure built for a different century. Spreadsheets lock when two people open them. Freezer inventories live in a senior postdoc's head. An estimated ten billion dollars is spent every year in the United States rebuying reagents already sitting on a shelf nobody could find. In this conversation, Jacob Lee and Jin Cho — co-founders of GeneMode — describe what they saw when they looked at that infrastructure as outsiders and as scientists at once. Lee is a bioengineer whose first year of graduate school was defined by scheduling thirty-minute appointments on a senior postdoc's calendar just to access the lab's inventory software, and that experience is what turned frustration into a company. Cho came from engineering software for military drones at General Atomics, and was stunned when he saw what his friend's lab was paying for a tool that looked straight out of Windows XP. They talk about the slow architecture of drug discovery, the compounding cost of irreproducibility, and why rebuilding the tools scientists use every day is, for them, the most direct path to getting cures to patients faster. About the Guests Jacob Lee is the CEO and co-founder of GeneMode. He trained as a bioengineer and worked as a research scientist in stem cell and cancer labs before founding the company. His frustrations as a first-year graduate student navigating inaccessible lab software became the seed for GeneMode. He leads the company's product vision, focused on inventory, experiment management, and research reproducibility. Jin Cho is the CTO and co-founder of GeneMode. Trained in electrical and computer engineering, he began his career at General Atomics building software for military drones before reuniting with his high-school friend Lee to rebuild research tools from the ground up. At GeneMode he leads the engineering team and the platform's weekly release cycle. Scientific Themes of the Conversation The cost of irreproducibility — waste, delay, and the compounding friction of bad tools Access asymmetry in research — who gets to use the lab's software, and who waits Research software as infrastructure — why tools built for scientists behave differently than tools adapted to them The drug discovery timeline — preclinical, clinical, and regulatory phases, and where software actually matters Collaboration in shared labs — real-time editing, shared freezers, and the Excel-lock problem Lab automation and the hidden operating cost of being a scientist Key Insights from the Conversation Ten billion dollars vanishes every year into duplicate reagent orders. Lee describes an estimate that American labs spend roughly ten billion dollars annually on reagents they already own but can't locate. The cost isn't just money — it's the erosion of reproducibility that follows from not knowing what's in the freezer. Access to the lab's tools is often rationed by seniority. In Lee's first graduate lab, only the principal investigator and a senior postdoc had logins for the expensive inventory software. As a student, he scheduled thirty-minute appointments on a postdoc's calendar to learn how to use a tool the lab had already paid thousands of dollars for. Excel is the default research tool because no one built a better one for scientists. The co-founders argue that most lab software wasn't built for scientists — it was built for general business use and retrofitted. That explains the locked files, the manual re-entry, the outdated look, and the poor fit with how research actually moves. Lab infrastructure is the hidden variable in drug discovery timelines. COVID-era conversations about why vaccines take eighteen months tend to focus on the clinical and regulatory phases. Lee reframes the question toward the preclinical phase, where data management and reproducibility quietly compound every delay downstream. Private and shared workspaces both matter, even in collaborative labs. Cho and Lee describe designing for the reality of shared benchwork: most labs want everything visible to everyone, but individual scientists still need space for protocols-in-progress or personal collections they're not ready to publish internally. Fast release cycles are a signal of infrastructure maturity. Cho describes shipping updates weekly, prioritizing customer-reported bugs and feature requests with a design-to-test-to-ship loop that most scientific software vendors don't attempt. That cadence is itself a philosophical statement about who the tool serves. A ninth-grade English class is an unlikely origin for scientific infrastructure. The GeneMode story starts with two teenagers in the same high-school classroom, different majors, different career paths, and a late-night message asking whether lab software could be hacked together in a weekend. The answer turned out to be no — but the question turned into a company. Episode Timeline Timestamps were generated using AI for readability. 00:00 Summit week welcome and episode introduction 01:34 Meeting the co-founders — CEO Lee and CTO Cho 03:11 From stem cell research to bioengineering frustration 04:03 The ninth-grade English class where the story starts 04:59 Seeing Windows XP-era software inside a modern lab 07:01 What GeneMode actually does that Excel can't 10:15 Onboarding a ten-person lab onto one shared platform 12:18 Ten billion dollars in wasted reagents 16:13 What's coming next — tools across the experimental lifecycle 18:32 Algorithms that predict when reagents will run out 22:43 A weekly release cycle built around user feedback 24:13 Why vaccines still take eighteen months Selected Quotes "A lot of the problems that we're solving is around data sharing for scientists — by having inventory, experiment management, applications, and data all in one collaborative workspace." — Jacob Lee "It looks like software that was built a couple of decades ago. And what surprised me even more was his lab was paying thousands of dollars for this legacy-looking software. I was mind-blown." — Jin Cho "In a lab of ten people, only the principal investigator and a very senior postdoc had access to the software. And as a student, I had to actually schedule times on my postdoc's calendar in thirty-minute segments just to learn how to use that tool." — Jacob Lee "The end goal is really much bigger than helping scientists manage their research projects or inventory. Our mission is to make that research repeatable and reproducible so that we can get those cures faster." — Jacob Lee About this episode In this special episode of the Dr.GPCR podcast , I sat down with the co-founders of Genemod . Jacob Lee and Jin Choe met in ninth grade in English class and have been friends since. Although both went to the same college, Jacob and Jin choose different career paths. One day as they were catching up, Jacob shared his struggles of managing samples and an incredible amount of data and projects in the lab with Jin. Our of this need Genemod was born. Today, Genemod has built a freezer management tool and a project management tool where scientists can manage their reagents, samples, and projects on one intuitive platform. The team is planning on building even more tools that will make Genemod the go-to platform for all research scientists to make research more efficient. Genemode on the web Website Jacob Lee on LinkedIn Jacob Lee on Dr. GPCR Ecosystem Jin Choe on LinkedIn Jin Choe on Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

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. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Aurélien Rizk About Dr. Aurélien Rizk "Dr. Aurélien Rizk is a scientist and entrepreneur in drug discovery. He is Chief Scientific Officer and co-founder of InterAx Biotech, where he specializes in the development of a technology platform deciphering cell signaling pathways combined with AI-based approaches to elucidate structure to signaling relationship. During four years of postdoctoral research at ETH Zurich and the Paul Scherrer Institute in Switzerland, under the guidance of Prof. Gebhard Schertler, he developed methods for kinetic mathematical analysis of GPCR signaling. He also worked on creating novel methods for systems biology using temporal logic specifications while pursuing his Ph.D. at INRIA Paris-Rocquencourt, France. Before focusing on the development of innovative mathematical modeling and simulation methods for drug discovery, Dr. Aurélien Rizk co-founded Algorizk, a company that created real-time physics simulations for education, serving over 1 million users. His academic background includes studies in mathematics, physics, and computer science at the French Grande École, École Normale Supérieure de Cachan." Dr. Aurélien Rizk on the web InterAx Biotech Paul Scherrer Institut The Org LinkedIn Google Scholar Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina Berchiche and Aurelien Rizk engaged in a conversation about their professional backgrounds and current projects. They explored the potential of merging mathematical models with biology, the complexities of GPCRs within cells, and the applicability of technology to other fields. They also discussed the founding of a company focused on GPCRs, the transition from academia to the biotech sector, the evolution of a company that started with the development of technologies combining mathematical methods and a wet lab, and the importance of interdisciplinary teamwork in drug and technology development. They emphasized the significance of mathematical models in systems biology and pharmacology and the challenges of transferring information between different families of GPCRs. They wrapped up the conversation by discussing job opportunities at Interax Biotech and their anticipation for future interactions. Summary Professional Backgrounds and Projects Discussed Yamina Berchiche and Aurelien Rizk had a conversation about their professional backgrounds and current projects. Aurelien Rizk, a co-founder and CEO of Interax Biotech, shared about the company's development of a discovery platform for GPCRs and their focus on signaling pathways. He also talked about his past experiences in mathematics, physics, and computer sciences, and his involvement in developing mathematical models for various systems. The discussion concluded without any clear decisions, action items, or open questions. Integrating Mathematical Models and Biology: A Fascinating Discussion Yamina and Aurelien Rizk had a conversation about the importance of merging mathematical models and biology. They highlighted that while there was a time when biology lagged due to the lack of appropriate tools, it is now progressing faster. They found it fascinating to integrate both fields and the potential it holds. Aurelien Rizk mentioned the importance of being able to test and adjust predictions in real-life scenarios. They also touched upon the transferability of this approach across different systems, which Yamina found attractive. GPCRs, Software, and Fluid Dynamics Yamina Berchiche and Aurelien Rizk discussed the complexities of GPCRs within cells and the potential for applying models from one system to another. Yamina also questioned Aurelien Rizk about his interest in software, computer science, and mathematics. Aurelien Rizk shared his journey of using these disciplines in biology and how his company, Interax, came to be. The discussion ended with Aurelien Rizk sharing his current work on numerical simulations of fluid dynamics. GPCRs: A Focus for New Company Aurelien Rizk and Yamina Berchiche discussed the founding of a company focused on GPCRs and the potential applicability of the technology to other fields. Aurelien Rizk shared that he had always focused on GPCRs but had also worked on other types of receptors, indicating that the technology could be applied broadly. Yamina asked if there was ever a consideration to work on targets other than GPCRs, to which Aurelien Rizk explained that they chose GPCRs due to their wide application and potential impact. The conversation concluded with Yamina asking if Aurelien Rizk had a favorite GPCR to work on, though his response was not included in the transcript. Cell Signaling and Cancer Metastasis Discussion Aurelien Rizk and Yamina Berchiche had a detailed conversation about the intricacies of cell signaling and chemokine receptors. Yamina shared her research experience, emphasizing the fascination of understanding how cells respond to gradients and signals, particularly in relation to cancer metastasis. Aurelien Rizk also contributed to the conversation, highlighting the complexity of the process. However, the transcript is somewhat unclear and disjointed, making it difficult to summarize the specific points discussed. Academia to Biotech: Strategic Planning and Interdisciplinary Approach Yamina Berchiche and Aurelien Rizk discussed the differences between academia and the biotech industry, with Aurelien Rizk sharing his experiences transitioning from academia into the biotech sector. They highlighted the strategic importance of planning in the biotech sector due to limited funds and the need to show positive results when securing new investments. Aurelien Rizk also mentioned the interdisciplinary nature of his company, which includes mathematics, signaling pathways, a wet lab for data generation, and AI and computational chemistry. The discussion also touched on recent changes in leadership at Aurelien Rizk's company, with the introduction of a new CEO a year ago and the valuable contributions of Mark Levick, a former reviewer for the European Medicines Agency and CEO of a biotech company. Technology Evolution and Ligand Residence Time Prediction Yamina Berchiche and Aurelien Rizk discussed the evolution of the company, which started with the development of technologies combining mathematical methods and a wet lab to ensure the technology functioned. They validated their technology and made collaborations for expertise on chemokine receptors. The conversation also revolved around the company's ability to predict the residence time of a ligand and its potential correlation with a therapeutic effect or activation of a specific signaling pathway. The discussion concluded with the idea that ligand residence time could be an important factor in effective therapy. Therapeutic Effect and Receptor Interactions Aurelien Rizk and Yamina had a detailed discussion about the importance of gaining more information about the therapeutic effect in patients or animals and the dynamics of receptor interactions. They emphasized the need to quantify the dynamics of the pathways and the residence time of the receptor. Yamina raised a question about the transferability of information between different families of GPCRs and the possibility of generating a mathematical model for potential patterns. They also discussed the challenges of system dependency in data and the need to express data in a uniform way to apply models. Mathematical Models in Systems Biology and Pharmacology Aurelien Rizk and Yamina discussed the importance and relevance of mathematical models in systems biology and pharmacology. They reminisced about previous meetings and events, including a GPCR retreat where Terry presented his work. Yamina mentioned her struggle with the mathematical aspects of Terry's papers but acknowledged their importance in quantifying and removing system biases. They also discussed plans to offer a course with Terry, due to high interest. Towards the end, Aurelien Rizk shared his top three 'aha' moments as a scientist, emphasizing the importance of learning and controlling systems. Interdisciplinary Teamwork and Drug Development Yamina Berchiche and Aurelien Rizk emphasized the significance of interdisciplinary teamwork in drug and technology development, noting the challenges of communication and collaboration across different fields. They also shared their preference for small molecule therapies over protein therapeutics. Aurelien Rizk confirmed his attendance at the upcoming GPCR-Targeted Drug Discovery Summit in Boston. The discussion concluded with a brief overview of job opportunities at Interax Biotech, with Aurelien Rizk and Yamina clarifying that job openings are communicated via email and through their job board. They expressed their anticipation for future interactions. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

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