Insects that transmit disease often detect humans through olfactory cues, making it imperative to better understand how odors are encoded and elicit behavior in insects. The long term goal of this proposal is to illuminate fundamental processes in insect olfactory signaling, with particular focus on a subset of olfactory neurons, coeloconic neurons, known to detect human odorants. Given the evolutionary conservation of olfactory systems amongst insects, we propose to make use of the genetic and behavioral tools available in Drosophila to understand the molecular basis of attraction to these odorants. In my first aim, I will expand the range of odors known to activate coeloconic neurons by characterizing their responses to additional odorants using electrophysiological recordings. In particular, I will focus on amines and carboxylic acids, attractive odors found in human emanations. In my second aim, I will dissect the behavioral significance of coeloconic neuron signaling by utilizing genetic manipulations and a well-characterized behavioral assay with adult flies. Finally, I will identify additional signaling components enriched in coeloconic ORNs that are necessary for olfactory receptor activity by probing the function and localization of candidate genes obtained from an RNA Sequencing screen. Together, these experiments are designed to elucidate molecular mechanisms of olfactory signaling and the means by which environmental signals are transformed into behavior in insects. PUBLIC HEALTH RELEVANCE: Insect-borne diseases, including malaria, kill more than a million people each year. Insects such as mosquitoes primarily rely upon their olfactory system to detect humans. This project is designed to shed light on how human odorants are encoded and elicit behavior in insects. The results could lead to the development of improved insect repellents and traps.