Decoding Human Odor Detection in Aedes aegypti: Mapping Odorant Receptor Pathways for Global Health Applications

Abstract

Aedes aegypti is a highly effective vector of mosquito-borne diseases such as Dengue, Zika, Chikungunya, and Yellow Fever. Its strong preference for human hosts is largely driven by olfactory cues, making the mosquito’s olfactory system a critical area of study for understanding and mitigating disease transmission. This thesis investigates the organization of olfactory sensory neurons (OSNs) and their projections to specific glomeruli in the antennal lobe, with a focus on five odorant receptors (Or6, Or16, Or23, Or52, and Or94) that may play roles in human odor detection. Using transgenic mosquito lines generated through CRISPR and the Q-binary expression system, fluorescently labeled olfactory sensory neurons (OSNs) were visualized via confocal microscopy. Glomerular positions were mapped and compared to existing anatomical and molecular atlases to propose new receptor–glomerulus pairings. Additionally, glomerular volumes were calculated using 3D reconstructions in ImageJ, and receptor expression was quantified across antennal segments to examine spatial distribution patterns. Results show preliminary evidence for assigning Or6 and Or94 to glomeruli PD1 and V3, respectively, and suggest revised candidate glomeruli for Or16, Or23, and Or52 based on anatomical alignment and RNA expression data. These findings contribute to a more comprehensive understanding of the Ae. aegypti olfactory system and offer valuable targets for future studies exploring host-seeking behavior and vector control. By identifying key olfactory circuits involved in human odor detection, this work supports the broader goal of disrupting mosquito-human interactions to reduce disease burden.