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Updated: Jan 26, 2026

High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity
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High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity

Published on: June 2, 2014

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Rapid Deorphanization of Human Olfactory Receptors in Yeast

Emily A Yasi1, Sara L Eisen1, Hanfei Wang1

  • 1School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States.

Biochemistry
|April 13, 2019
PubMed

Insights

Researchers identified new ligands for colon olfactory receptors (ORs), enabling studies on host-microbiome communication and the neuroscience of olfaction. This work advances understanding of ectopic OR functions in various tissues.

Area of Science:

  • Neuroscience
  • Gastroenterology
  • Microbiology

Background:

  • Ectopic olfactory receptors (exORs) are found in over 16 tissues, but their functions are poorly understood due to a lack of identified ligands.
  • Olfactory receptors in the colon are particularly interesting for studying host-microbiome interactions in this diverse microbial environment.

Purpose of the Study:

  • To deorphanize specific olfactory receptors highly expressed in the colon.
  • To identify novel ligands for colon exORs, facilitating research into their roles in host-microbiome communication.

Main Methods:

  • Utilized a G-protein-coupled receptor (GPCR)-based yeast sensor strain to create sensors for seven colon ORs.
  • Screened these colon OR sensors against 57 chemicals known to interact with olfactory receptors.

Main Results:

  • Successfully deorphanized two colon exORs, OR2T4 and OR10S1, for the first time.
  • Identified alternative ligands for the OR2A7 receptor.
  • Demonstrated a workflow applicable to deorphanizing other GPCRs.

Conclusions:

  • The identification of ligands for OR2T4, OR10S1, and OR2A7 enables future studies on their functions within the colon.
  • Developed colon OR-based sensors can be used to discover endogenous colon metabolites that activate these receptors.
  • This research contributes to the neuroscience of olfaction and understanding exORs in non-olfactory tissues.

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