NOV 09, 2016 09:00 AM PST

A duplexed assay to measure GPCR-mediated calcium signaling and β-Arrestin recruitment from single well using FDSS/µCell functional screening system

SPONSORED BY: DiscoverX, DiscoverX
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  • Head of Molecular and Cellular Pharmacology, Bioprojet Biotech
      Dr. Thierry Calmels is currently heading the Molecular and Cellular Pharmacology department at Bioprojet Biotech, with a focus on Neuroscience and Inflammation therapeutic areas. Dr. Calmels' main research focus is on G-protein Coupled Receptors (GPCRs) with the aim of setting up screening and secondary assays, as well as to dissect their signaling mechanisms for proposed drug targets. Dr. Calmels has specialized in implementing calcium mobilization assays for GPCRs in drug discovery as well as for human iPSC-derived cardiomyocytes in cardiac safety. Dr. Calmels got his Ph.D. in Applied Genetics at the University of Toulouse (France), after which he moved to Pittsburgh (USA) for a Post-Doc in Pharmacology with Dr. J. Lazo. After spending 3 years in Pittsburgh, Dr. Calmels joined the Molecular Oncology department with Pr. D. Stéhelin at the Pasteur Institute in Lille, France, followed by 5 years at GlaxoSmithKline (GSK) within the Cardiology Unit before joining Bioprojet in 2001.

    DATE: November 9th, 2016
    TIME: 9:00 AM PT, 12:00 PM ET

    The screening and functional characterization of novel ligands for G-Protein Coupled Receptors (GPCR) remains a key focus in drug discovery. Of late, an increasing awareness of the subtleties of receptor signaling and potential for ligand bias requires multiple endpoints to be monitored for the same screening campaign. In addition, efforts to reduce costs and improve efficiency of screening are always a key consideration for any screening campaign. In this webinar, we describe a duplexed assay for the Histamine H1 receptor using the PathHunter β-arrestin clonal cell line from DiscoverX. We have adapted existing assay protocols to monitor intracellular calcium signaling in real time along with the recruitment of β-arrestin to the Histamine H1 receptor, from the same well on a plate. We discuss protocol development and successful implementation of the final assay with this multiplexing approach, through data presented on Histamine H1 agonists and antagonist pharmacology. This duplexed assay clearly demonstrates an overall increase in screening efficiency and a total reduction in cost for running similar screening, lead optimization, and characterization programs for GPCR drug discovery.
    Learning Objective 1 : Screening approaches for GPCR drug discovery
    Learning Objective 2 :Creating a duplexed assay to monitor Calcium and β-arrestin in a single well

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