# Olfactory and gustatory detection of aversive skin compounds by mosquitoes

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2024 · $505,238

## Abstract

ABSTRACT
 Mosquitoes use their olfactory and gustatory systems to find and land on a human host’s skin for a blood
meal, and in the process transmit diseases like Dengue to hundreds of millions of people worldwide. Therefore,
the two chemosensory systems are excellent targets for behavior disruption strategies. The gustatory system, in
particular, plays the most critical role in avoidance of the synthetic topical insect repellent DEET, however it has
not been leveraged for discovery of improved repellents. There is a huge need for better topical repellents; the
poor cosmetic properties and high cost for frequent application on the skin preclude the use of DEET by high-
risk populations in tropical countries. We reasoned that new behavioral actives could be identified from human
skin-associated compounds, the rationale being that anthropophilic mosquitoes, such as Aedes aegypti, exhibit
different preferences for individual humans based on differences in skin chemistry. In a recent breakthrough we
developed a Machine Learning cheminformatic method to predict odorant and tastant repellents from in silico
screening of skin-associated compounds. In preliminary testing using behavior assays, we found powerful
repellent effects from components of skin volatiles, sweat and even microbiome metabolites. The overarching
goal of this proposal is to identify skin compounds that affect close-range mosquito landing behavior and perform
an analysis of the cellular and receptor pathways (Or, Ir, Gr or TrpA1) that are required to sense these
compounds in olfactory and gustatory neurons of Ae. aegypti. The objective will be achieved via three specific
aims. First, we will validate the computationally-predicted skin repellents in mosquito behavioral assays designed
to evaluate close-range (olfactory) and contact-dependent (gustatory) effects, which will create priority lists for
the following aims. Second, compounds that act upon contact or are non-volatile will be prioritized for surveying
gustatory responses with single sensillum electrophysiology and in assays to examine residency and probing
behaviors, which occur after landing in preparation for blood feeding. Testing Gr and Ir co-receptor mutants will
identify chemoreceptor pathways involved in sensing any taste-active repellents. Third, compounds that are low-
volatility and act at close range (like DEET) will be prioritized for surveying olfactory responses with
electrophysiology. Contributions of chemoreceptor pathways involved in sensing the olfaction-active repellents
will be identified by testing Orco and Ir co-receptor mutants. Finally, we will test if blends of predicted skin
repellents that act on both olfactory and gustatory pathways can alter host attractiveness. Successful completion
of this proposal will provide a foundation for understanding how aversive components of complex skin-associated
cues can alter mosquito-host interactions at close range.

## Key facts

- **NIH application ID:** 11125022
- **Project number:** 1R56AI180224-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Anupama Arun Dahanukar
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $505,238
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11125022

## Citation

> US National Institutes of Health, RePORTER application 11125022, Olfactory and gustatory detection of aversive skin compounds by mosquitoes (1R56AI180224-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11125022. Licensed CC0.

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