A Scalable, Multiplexed Assay for Decoding GPCR-Ligand Interactions with RNA Sequencing.

Journal Article (Journal Article)

G protein-coupled receptors (GPCRs) are central to how mammalian cells sense and respond to chemicals. Mammalian olfactory receptors (ORs), the largest family of GPCRs, mediate the sense of smell through activation by small molecules, though for most bonafide ligands, they have not been identified. Here, we introduce a platform to screen large chemical panels against multiplexed GPCR libraries using next-generation sequencing of barcoded genetic reporters in stably engineered human cell lines. We mapped 39 mammalian ORs against 181 odorants and identified 79 interactions that have not been reported to our knowledge, including ligands for 15 previously orphaned receptors. This multiplexed receptor assay allows the cost-effective mapping of large chemical libraries to receptor repertoires at scale.

Full Text

Duke Authors

Cited Authors

  • Jones, EM; Jajoo, R; Cancilla, D; Lubock, NB; Wang, J; Satyadi, M; Cheung, R; de March, C; Bloom, JS; Matsunami, H; Kosuri, S

Published Date

  • March 27, 2019

Published In

Volume / Issue

  • 8 / 3

Start / End Page

  • 254 - 260.e6

PubMed ID

  • 30904378

Pubmed Central ID

  • PMC6907015

Electronic International Standard Serial Number (EISSN)

  • 2405-4720

Digital Object Identifier (DOI)

  • 10.1016/j.cels.2019.02.009


  • eng

Conference Location

  • United States