# Molecular Mechanisms of Sugar Sensing by Insect Gustatory Receptors

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $353,319

## Abstract

PROJECT SUMMARY
Animals desire sugars for their energy potential and for the pleasurable sensation of tasting sweetness. Despite
the importance of sugar receptors in influencing nutrient sensing, metabolic responses, and taste perception,
few studies have been performed to identify the molecular mechanisms underlying sugar detection and
recognition. The proposed project will address this gap by integrating structural and functional studies to offer a
unique perspective on the biophysical basis for sweet taste. In the first two Aims, we will focus on a single
exemplary GR, Gr9 from the silk moth Bombyx mori, and couple structural methods with mutagenesis and
functional assays to understand why it can only be activated by a single type of sugar, D-fructose. In Aim 1, we
will investigate how this receptor binds D-fructose, how binding is coupled to the channel gate, and how different
subunits within the tetramer interact cooperatively to open the ion-conducting pore. In Aim 2, we will investigate
why other similarly sized sugars bind but do not activate the channel. In Aim 3, we will expand our analysis to
other GRs that are activated by different sweet compounds to resolve the relationship between receptor
sequence and ligand specificity. Our structural and functional analyses of GRs will provide a crucial foundation
to understand how different tastants are recognized by a diverse collection of receptors and present novel routes
for the design and optimization of small molecules that interfere with the gustatory systems of insect vectors of
human pathogens.

## Key facts

- **NIH application ID:** 10802517
- **Project number:** 1R01GM149636-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Joel Adam Butterwick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $353,319
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802517

## Citation

> US National Institutes of Health, RePORTER application 10802517, Molecular Mechanisms of Sugar Sensing by Insect Gustatory Receptors (1R01GM149636-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10802517. Licensed CC0.

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