# Mechanisms of chemosensory recognition

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $428,743

## Abstract

ABSTRACT
The olfactory system encodes and analyzes odorants. Chemicals bind to members of large families of receptor
proteins tuned to different chemical features. While we have a comprehensive inventory of the receptor genes
that underlie olfactory detection, we are far from having a similarly comprehensive understanding of the
chemical features detected by olfactory systems.
 This proposal leverages four developments—the ability to record the output of an entire olfactory
system (the vomeronasal system), a large and structurally-rigid class of odorants (sulfated, carboxylated, and
glucuronidated steroids), a new tool to identify the receptor gene(s) that have particular ligand detection
profiles, and a new tool for ectopically expressing a chosen receptor gene and studying its function—to
develop the first system-wide understanding of how an olfactory system represents the chemical world. The
overarching goal is to develop insights analogous to (and with similar predictive power to) the role of cone
photoreceptor tuning curves in our understanding of color vision.
 The specific aims of the proposal are (1) to reveal new principles of combinatorial coding through a
system-wide analysis of the vomeronasal system’s coverage, redundancy, and specificity via a large ligand
screen and quantitative analysis of the structural features required for activating each receptor; and (2) to
reveal relationships between receptor sequence and odorant structure by deorphanizing a large subfamily of
vomeronasal receptor genes. Preliminary data suggest that structural rigidity of steroid metabolites
contributes greatly to the tractability of these aims, supporting quantitative and predictive analysis on a
system-wide scale.

## Key facts

- **NIH application ID:** 10870101
- **Project number:** 5R01DC020034-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Timothy Holy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $428,743
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870101

## Citation

> US National Institutes of Health, RePORTER application 10870101, Mechanisms of chemosensory recognition (5R01DC020034-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10870101. Licensed CC0.

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