Why Mosquitoes Hunt You: The GPCR Behind the Bite

How does ligand binding at the extracellular pocket of a GPCR reshape signaling on the intracellular side?Biased agonism is often measured through pathway activation assays, but the structural origin of ligand bias remains difficult to trace. Can molecular simulations reveal the communication routes that link ligand binding to G protein or arrestin signaling?In this conversation, computational biologist Anita Niveda explores how molecular dynamics and network analysis can map allosteric communication within GPCRs—revealing how microscopic structural pathways relate to macroscopic signaling outcomes. From discovering bioinformatics as an undergraduate to developing computational methods for quantifying ligand bias, the discussion moves through the scientific thinking behind modeling receptor signaling, collaborations between academia and industry, and how computational tools are becoming predictive instruments in drug discovery.Key Topics in This EpisodeHow molecular dynamics simulations reveal communication pathways connecting ligand binding sites to G protein or arrestin interfacesWhy mapping allosteric communication networks helps explain biased agonism in GPCR signalingWhat computational strategies can quantify ligand bias directly from receptor structuresHow receptor subtype selectivity emerges from subtle structural and dynamic differences in binding pocketsWhy academic–industry collaborations can accelerate method development in receptor pharmacologyWhat career decisions shape the path from computational biology training to drug discovery rolesTimestamps0:00 A structural question behind ligand bias1:30 Introduction and scientific background3:40 Discovering bioinformatics and computational biology7:30 First encounters with GPCR structural biology9:40 Finding and choosing a postdoctoral lab16:40 Entering GPCR research and allosteric communication18:20 Quantifying ligand bias using simulations20:00 Mapping signaling pathways through receptor residues23:30 Academic–industry collaboration with Boehringer Ingelheim27:00 Moving from academia to industry research35:00 Interviewing and transitioning into biotech45:00 Aha moments in computational GPCR research50:00 The diversity of GPCR families and signaling biologyKeywords: GPCR podcast, GPCR signaling, biased agonism, drug discovery, receptor pharmacology

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

Key TakeawaysHow does the precise localization of GPCRs in lipid rafts reshape drug discovery strategy? Examine implications for functional assays and therapeutic innovation.Explore the pivotal role of GPCR-lipid raft compartmentalization in receptor signaling, desensitization, and pharmacology research. Dr. Keyvan Sedaghat discusses assay approaches, regulatory mechanisms, and the translational impact of bitter taste receptors beyond sensory biology. Leveraging decades of experience in assay development and database creation, he offers actionable insights for researchers optimizing GPCR drug discovery pipelines.Compartmentalization of GPCRs in lipid rafts directly influences receptor signaling and drug response.Desensitization pathways of dopamine D1 receptors depend on precise phosphorylation domains—challenging classical paradigms.Bitter taste receptors demonstrate functional relevance in non-gustatory tissues with emerging therapeutic applications.Database-driven research accelerates the identification of receptor-microdomain interactions for novel targets.Integration of computational modeling and biochemical validation is essential for advancing GPCR assay strategies.Dr. GPCR Links & ResourcesAccess the Dr. GPCR Ecosystem at https://www.ecosystem.drgpcr.com/ for community, tools, and databases.Details on Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricingGPCR Weekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-newsExplore Dr. GPCR Premium for expanded translational resources and networking.About the GuestDr. Keyvan Sedaghat holds a pharmacy degree and a PhD in cellular and molecular medicine, specializing in pharmacology, from the University of Ottawa. With over two decades of academic experience, he has served as a professor, senior lecturer, and chief scientific officer in the pharmaceutical and cosmetic industries. Dr. Sedaghat’s work spans peer-reviewed publications and editorial roles across journals in molecular pharmacology, cell signaling, and G protein-coupled receptors. His scientific drive centers on unraveling molecular mechanisms underlying GPCR function and translating those findings into effective teaching, research, and drug discovery strategies.Guest on the Web:LinkedInGoogle Scholar

Episode SummaryPotent in vitro hits often fail in vivo—Martin Marro details how robust assay choice and pathway deconvolution can revive GPCR drug discovery programs.Listeners will learn practical approaches to assay development for GPCR drug discovery, the pitfalls of calcium readouts, and how identifying pathway bias impacts translational success. Dr. Marro shares his experience bridging in vitro–in vivo gaps, refining selection flowcharts, and leveraging pharmacology research to drive clinical candidates. His strategic perspective is rooted in years of leading multimodal discovery teams in pharma and biotech. Key TakeawaysAssay selection critically shapes the trajectory from hit to clinic.Calcium and IP1 assays may not predict in vivo efficacy for all Gq-coupled receptor targetsAlternative pathway analysis may be essential for mechanism elucidation.Persistence in probing beyond standard readouts can rescue high-profile discovery programs. Team structure and collaborative problem-solving are pivotal in resolving translational bottlenecks.Explore Dr. GPCR Resources- Dr. GPCR Ecosystem- Membership & Pricing- Weekly NewsExplore the full depth of GPCR resources, events, and member-exclusive tools with Dr. GPCR Premium.About the GuestDr. Martin Marro leads the Cell Pharmacology group in the DOCTA division at Lilly’s Seaport Innovation Center in Boston, MA. Trained as a pharmacologist, Dr. Marro has accumulated over 20 years of experience spanning large pharmaceutical firms—including GSK, Novartis, and Lilly—and innovative biotech such as Tectonic Therapeutic. He holds deep expertise in early drug discovery across small molecules, peptides, and antibody therapeutics for metabolic, cardiovascular, and gastrointestinal diseases.Dr. Marro’s research has been central to the discovery and characterization of multiple clinical candidates, with a focus on GPCR target validation, receptor pharmacology, and translational assay strategies. He played a key role in patenting and developing novel fatty acid-conjugated GLP-1 receptor agonists. Driven by the challenge of translating robust in vitro science into clinical proof-of-concept, Dr. Marro’s leadership continues to impact the field of GPCR drug discovery.Keywords: gpcr podcast, assay development, pharmacology research.

GPCR tools don’t move the field forward unless researchers can actually use them. This episode breaks down how collaboration turns probes into progress.SummaryIn the final episode of this series, David Hodson, Johannes Broichhagen, and Maria Majellaro unpack how academic labs and Celtarys Research partnered to scale fluorescent probes, improve assay development, and support gpcr drug discovery. The conversation spans receptor internalization, fluorescence assays, tech transfer realities, and why tool availability—not just invention—drives translational pharmacology research.Key takeawaysWhy accessibility defines the real impact of GPCR toolsHow industry enables scalable assay developmentLessons from receptor internalization studies in complex tissuesWhat makes academia–industry collaborations actually workRead more here: https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/scaling-glp-1-receptor-tools-through-academia–industry-collaboration

Chemical probes are reshaping how we map GLP-1R in real time — revealing receptor pools antibodies can’t reliably capture.This is Episode 2 of a 3-part GPCR tool-development series created in partnership with Celtarys Research.Summary:Dr. Johannes Broichhagen aka JB breaks down the design logic behind fluorophore-linked peptides, assay trade-offs, and what true receptor internalization looks like in live tissue. A concise masterclass in assay development and GPCR drug discovery.What you’ll learn:• Why antibody variability pushed JB toward chemical probe engineering• The design logic behind Luxendin-based fluorescent tools — and how structure guides function • What “good assay development” looks like when cells, tissue, and probe behavior collide• Behind-the-scenes stories from the collaboration with David Hodson• Why parallelized experiments matter for reproducibility and signal quality• How small-molecule probes outperform antibodies in live-cell and tissue imaging• The surprising breakthroughs that shifted JB’s entire research trajectory• Future directions: multi-color GPCR mapping, AI-guided ligand design, and in vivo chemical biology Dr GPCR Links & Resources:• Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/ • Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricing• Weekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

Precise receptor mapping is reshaping how we understand incretin biology. David Hodson explains how GPCR-targeted chemical probes reveal where GLP-1 and GIP receptors actually signal across pancreas and brain—and what this means for metabolic drug design.Learn how these tools refine gpcr drug discovery, clarify receptor internalization, and guide next-gen therapeutics.🎓 Join Dr. GPCR Premium for exclusive episodes + research tools → https://www.ecosystem.drgpcr.com/

What makes Monash a model for modern pharmacology? Dr. Michelle Halls reveals how collaboration, mentorship, and receptor organization shape today’s GPCR breakthroughs — from femtomolar signaling to cancer biology. A look inside a lab culture built on precision, openness, and impact.👉  Watch the complete episode: https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/leadership-luck-and-gpcr-signaling🎓 Join Dr. GPCR Premium for exclusive episodes + research tools → https://www.drgpcr.com/premium

Predicting, not just explaining, can change how we design GPCR-targeted drugs. Jens Carlsson reveals how modeling bridges structure, function, and pharmacology.Hear how predictive simulations shape assay development, GPCR drug discovery, and collaborations across disciplines.🎓 Join Dr. GPCR Premium for exclusive episodes + research tools → https://www.ecosystem.drgpcr.com/gpcr-university-pricing Watch the complete episode at https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/model-predict-discover

🔬 What if you could track GPCR internalization—no wash, high-throughput, and in endogenous systems?Discover how Dr. Eric Trinquet and Revvity built pH Sense, a next-gen fluorescence assay that redefines receptor internalization workflows. Learn assay trade-offs, tool design, and how to decode GPCR behavior with precision.🎓 Join Dr. GPCR Premium for exclusive episodes + research tools → https://www.ecosystem.drgpcr.com/gpcr-university-pricingWatch the complete episode at https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/from-rare-earth-probes-to-real-internalization-assays-the-ph-sense-story