Bridging Mass Spectrometry with GPCR Biology: Discovery of New Ligands and New Targets
Speaker
Wenqing Shui
ShanghaiTech University
Time
Venue
Online
Tencent
Abstract
G protein-coupled receptors (GPCRs) represent the largest class of cell-surface proteins and constitute a prominent family of therapeutic targets. Therefore, significant efforts have been invested on the identification of novel ligands that can modulate the activity of a GPCR target with high potency and selectivity. However, Due to limitations inherant to the most common techniques for GPCR ligand discovery, there is a pressing need for more efficient and unbiased ligand screening methods especially for the identification of allosteric modulators. Here we present a versatile affinity MS-based platform for the identification of chemical ligands towards GPCR targets in multiple forms. This new platform, when combined with omics technology or double-click chemistry, enables the discovery of a series of new GPCR modulators from either synthetic libraries or natural herbs.
On the other side, to improve our chances of identifying key regulators or potential drug targets from the GPCR family, we developed a proteomic approach aided by deep learning models for comprehensive profiling of transmembrane protein families in multiple mouse brain regions. Through revealing the transmembrane proteome remodeling landscape in the brain of a mouse depression model, our study led to the identification of two novel GPCR regulators of depressive-like behaviors.
Bio
Dr. Wenqing Shui is currently leading a research group of GPCR Omics & Ligand Discovery at iHuman Institute in ShanghaiTech University as Research Professor and Assistant Director of iHuman Institute. She has obtained her master degree from Fudan University and PhD from UC Berkeley. After a short industrial experience at Thermo Fisher Scientific, she returned to China to establish her independent research group. The main research interest of Shui Group is to develop high-throughput affinity MS techniques for the discovery of GPCR ligands with new chemical structures and unique pharmacological properties. In addition, Shui Group has developed experimental and bioinformatics approaches for in-depth transmembrane proteome analysis in tissues to facilitate potential drug target discovery from the GPCR superfamily. Her major research work has been published in Nature, Nat. Commun., Science Advances, Cell Research, ACS Central Science, etc.
