# Molecular and functional characterization of olfactory pathways in the arbovirus vector mosquito Aedes aegypti

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2024 · $79,085

## Abstract

Project Summary Abstract
Mosquitoes infect hundreds of millions of people with deadly pathogens every year. Since mosquitoes
identify humans and other important resources primarily via their sense of smell, the disruption of
mosquito olfactory systems has long been recognized as a potential strategy for controlling these
pathogens. For example, repellants that scramble or block the detection of odors may be used to push
mosquitoes away from humans and the areas where we live and work. Conversely, irresistibly attractive
blends of volatile chemicals may be deployed to pull mosquitoes into lethal traps. Despite some
advances in this area over the past decade, progress has been limited by the fact that the olfactory
systems of our most important vector mosquitoes remain largely uncharacterized. We know that
mosquitoes detect odors using hundreds of ligand-specific olfactory receptors expressed in ~60 different
types of odor-sensing neurons scattered across their antennae and maxillary palps. But we don’t yet
know exactly which of these neurons mosquitoes use to detect humans nor which receptors are
expressed in those neurons. The parent award of this administrative supplement aims to characterize the
molecular and functional properties of all major odor-sensing cell types on the antennae of biting females
of the dengue, yellow fever, and zika vector mosquito Aedes aegypti. In Aim 1, we proposed to identify
the molecular receptors expressed in each of the ~60 types of odor-sensing neurons using single-
nucleus RNA sequencing. This work has been completed successfully and is currently being prepared
for publication. In Aim 2, we proposed to generate the genetic tools necessary to manipulate each type of
odor-sensing neuron using CRISPR/Cas9 genome editing. This work is in progress. In Aim 3, we
proposed to use the genetic tools from Aim 2 to identify the chemical odorants detected by each odor-
sensing neuron type. This third aim represents a critical final step in our overarching goal to determine
exactly which odor-sensing neurons mosquitoes use to detect humans. However, it requires the use of a
sophisticated two-photon microscope for imaging neural responses in odor-sensing neurons, and this
microscope recently malfunctioned. In this application, we are requesting an administrative supplement
to cover the cost of the unexpected repair to this microscope. Without these funds, we will not be able to
complete the goals of the parent award. Taken together we expect to generate a receptor-neuron-ligand
map for Aedes aegypti vector mosquitoes and a library of genetic tools with which to manipulate them—
opening the door to the efficient and rational design of chemical repellants and attractants for use in
vector control.

## Key facts

- **NIH application ID:** 11132254
- **Project number:** 3R01AI175490-02S1
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Carolyn Sarah McBride
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,085
- **Award type:** 3
- **Project period:** 2024-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11132254

## Citation

> US National Institutes of Health, RePORTER application 11132254, Molecular and functional characterization of olfactory pathways in the arbovirus vector mosquito Aedes aegypti (3R01AI175490-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11132254. Licensed CC0.

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