The broad long-term objective of this research is to determine the molecular mechanisms underlying detection of volatile odorants and pheromones in Drosophila melanogaster. This work is significant because insects transmit devastating diseases to humans and they use olfaction to find hosts and mates. Understanding these mechanisms will facilitate new approaches for its disruption. Drosophila is an excellent model system to reveal mechanisms underlying olfaction due to its wealth of genetic tools, including unbiased genetics screens. We recently found lipid translocation, mediated by the phosphatidylserine (PS) flippase dATP8B, is essential for normal odorant sensitivity. We are now leveraging this discovery to identify the components and pathways underlying lipid translocation and its relation to odorant sensitivity. This work represents a new path of investigation. Using a genetic screen, we identified a protein kinase C that genetically interacts with dATP8B and appears to transduce most of the effects of PS localization. We propose experiments to decipher how this kinase impacts olfaction. Aim 1 is to explore the role of PKC98E in olfaction by characterizing its localization in olfactory neurons, and evaluating the phenotype of null and dominant alleles to analyze the olfactory consequences. Aim 2 explores the role of conserved PKC phosphorylation sites in ORCO on olfactory sensitivity and receptor trafficking, and whether phosphorylation is odorant-dependent in vivo. Aim 3 is to identify additional components involved in this process from a pool of 35 pre-selected candidates to gain a more complete understanding of this mechanism. Successful completion of these aims will significantly advance our understanding of insect olfaction and may provide exciting insights into the role of lipid translocation in modulating olfactory signal transduction.