Female mosquitoes are vectors for some of the most debilitating infectious diseases of humans. Current chemical management strategies use insecticides that target the neuro-endocrine system almost exclusively. With insecticide resistance on the rise, there is a serious resurgence of mosquito-borne diseases, and therefore an urgent need to develop new targets for new strategies. Female of most mosquito species require vertebrate blood to provide nutrients for egg production and therefore need to locate an appropriate host mainly through their sense of smell. Consequently, mosquitoes have evolved an acute olfactory information processing system that detects and processes odor information to enable localizing the odor source, and finally rapidly inactivates the odor signal so as to maintain high odor sensitivity. Studies in the last several decades have greatly improved our understanding of how odors are detected and processed by the olfactory circuit, the neuroscience underlying odor-signal inactivation is poorly understood. Recent studies have suggested that antennal cytochrome P450s (CYPs) play an important role in odor molecule breakdown. In honeybees, a member of insect-specific CYP subfamily, CYP4G11, has been shown to degrade short-chain alcohols and aldehydes (common volatile odor molecules in plants and animal odor). The yellow fever mosquito, Aedes aegypti, has two functional CYP4G orthologs, CYP4G35 and CYP4G36. Our preliminary data show that CYP4G35 mRNA levels are highest in the head and peripheral olfactory tissues (antennae, maxillary palps, proboscis, and head). CYP4G35 knockdown by RNAi results in vertebrate host avoidance by the adults. Based on the evidence in the literature and our preliminary data, we hypothesize that the CYP4G35 is an odor degrading enzyme, important for odor clearance. We will test this hypothesis through two specific aims:
Aim 1) assessing the effects of CYP4G35 knockout on host and mate finding (olfaction and mating), and Aim 2) Functional determination of CYP4G35 as an odor degrading enzyme by determining enzyme substrates and localization in the antennae. We will employ techniques in molecular biology, biochemistry, and neuroscience/behavior to achieve these aims. This work will impact the field by providing 1) a novel target for mosquito control, and 2) an enhanced understanding of the olfactory information processing in mosquitoes.
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