MENU

The development and application of TRUPATH biosensors to the study of GPCR pharmacology and functional selectivity

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Exscientia Ltd
    Biography

      Dr. Reid Olsen is the head of GPCR Pharmacology at Exscientia Ltd. (Exscientia.ai), an AI-driven drug discovery biotechnology in Oxford, England. Dr. Olsen received his Ph.D. from the University of North Carolina at Chapel Hill under the mentorship of Dr. Bryan Roth. Dr. Olsen’s research spans multiple domains within pharmacology and neurobiology, but has been primarily focused on the development of biological tools for the study of GPCR signaling in vitro and in vivo.


    Abstract

    G-protein-coupled receptors (GPCRs) remain major drug targets, despite an incomplete understanding of how they signal through 16 non-visual G-protein signal transducers (collectively named the transducerome) to exert their actions. Recent efforts in GPCR drug discovery have included the design or discovery of drugs that alter the engagement of specific subsets of these pathways—a concept termed functional selectivity or “bias.” However, traditional pharmacological tools to classify and rank the pharmacological activity of test compounds have largely depended on intracellular signaling pathways downstream of receptor activation and are heavily dependent on the intracellular milieu unique to each cell type or tissue, i.e. “system bias.” Because multiple transducers can link to common pathways, the disambiguation of specific G protein pathways can be especially laborious. To overcome this, multiple teams have developed FRET and BRET tools that directly measure ligand-mediated receptor-transducer engagement, though these have been largely incomplete or incompletely characterized. This talk will describe the development, characterization, and validation of the largest set of GPCR-G protein biosensors to date, collectively dubbed TRUPATH. Specific emphasis will be placed on the versatility of these types of tools in drug-screening and receptor-characterization efforts. These biosensors are freely and openly available to academic researchers for modification and use through an MTA with the University of North Carolina at Chapel Hill or through distribution by Addgene, the non-profit plasmid repository.

    Learning Objectives:

    1. Describe the mechanism of G protein signalling and by what properties are they classified into their families

    2. What are some key considerations when defining FRET or BRET probes?

    3. In your own words, define or describe functional selectivity


    Show Resources
    You May Also Like
    MAY 11, 2021 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    MAY 11, 2021 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    Date: May 11, 2021 Time: 10:00zm PDT Your samples are some of the most valuable assets in the laboratory. After spending countless hours on extraction and preparation, your conclusions could...
    NOV 18, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 18, 2020 8:00 AM PST
    DATE: November 18, 2020 TIME: 08:00am PDT We develop and implement technologies to solve some of the major bottlenecks in biomedical research. In particular, we establish new imaging approac...
    OCT 29, 2020 6:00 AM PDT
    C.E. CREDITS
    OCT 29, 2020 6:00 AM PDT
    Date: October 29, 2020 Time: 6:00am (PDT), 9:00am (EDT), Chronic inflammation can occur as a result of a combination of genetic predispositions and environmental factors. Epigenetic modifica...
    NOV 16, 2020 8:00 AM PST
    C.E. CREDITS
    NOV 16, 2020 8:00 AM PST
    Date: November 16, 2020 Time: 8:00am (PST), 11:00am (EST) CRISPR screening has become the prime discovery tool in modern biomedical research and drug discovery. At the same time, most screen...
    APR 01, 2021 8:00 AM PDT
    C.E. CREDITS
    APR 01, 2021 8:00 AM PDT
    Date: April 01, 2021 Time: 8:00am (PST), 11:00am (EST) Generating therapeutic antibodies is far more challenging than obtaining antibodies that merely recognize their targets. Engineering po...
    FEB 24, 2021 10:00 AM PST
    C.E. CREDITS
    FEB 24, 2021 10:00 AM PST
    DATE: February 24, 2021 TIME: 10am PST Automated lab instruments such as liquid handlers and cell sorters are increasingly common in all types of laboratories, driving fast results for labor...
    Loading Comments...
    Show Resources
    Attendees
    • See more