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

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 17, 2022 9:00 AM PDT
MAY 17, 2022 9:00 AM PDT
Date: May 17, 2022 Time: 9:00am (PDT), 12:00pm (EDT), 8:00pm (CEST) Gene therapeutics have great potential to treat many severe diseases in an unprecedented, targeted manner. The biopharmace...
AUG 10, 2022 10:00 AM PDT
AUG 10, 2022 10:00 AM PDT
Date: August 10, 2022 Time: 10:00am PDT, 1:00pm EDT The global pandemic has increased focus and scrutiny on molecular diagnostic assay development, resulting in a need for assays that provid...
JUN 29, 2022 7:00 AM PDT
JUN 29, 2022 7:00 AM PDT
Date: June 29, 2022 Time: 7:00am (PDT), 10:00am (EDT), 4:00pm (CEST) Imaging live cells is key to reveal their inner workings, dynamics, and function. Current technological advances in confo...
APR 28, 2022 8:00 AM PDT
APR 28, 2022 8:00 AM PDT
Date: April 28, 2022 Time: 8:00am (PDT), 11:00am (EDT), 5:00pm (CEST) Human pluripotent stem cells (PSCs) and their derivatives hold great potentials in...
MAR 16, 2022 8:00 AM PDT
C.E. CREDITS
MAR 16, 2022 8:00 AM PDT
Date: March 16, 2022 Time: 8:00am (PDT), 11:00am (EDT), 5:00pm (CET) Handling of potent and/or hazardous substances is commonplace in sev.....
JUN 21, 2022 6:00 AM PDT
JUN 21, 2022 6:00 AM PDT
Date: June 21, 2022 Time: 6:00am (PDT), 9:00am (EDT), 3:00pm (CEST) The global understanding and practice of medicine is currently undergoing a revolutionary change. This shift to precision...
Loading Comments...
Show Resources