The overall objective of this research is to discover novel compounds that control the destructive behavior of insect disease vectors such as mosquitoes. Many insect behaviors, including the location and recognition of human hosts by mosquitoes, are governed by the detection of chemical cues in the environment via the sense of smell, olfaction. This sensory process is thought to occur by the binding of specific odorous ligands to a diverse family of G-protein-coupled odorant receptors (ORs) located on olfactory neurons in the antenna. The goal of this proposal is to establish a cell-based assay system to identify small molecules that activate or block OR function in the malaria mosquito Anopheles gambiae. In preliminary studies we have identified seven candidate OR genes from Anopheles. To identify chemicals that activate these candidate ORs, the following specific aims are proposed: (1) Using fruit fly (Drosophila melanogaster) ORs with known ligands, we will establish a calcium-based assay to monitor insect OR activity. (2) We will then express the Anopheles ORs in this assay system and examine the responses to a range of odorous compounds that mosquitoes are known to detect. The health relatedness of these studies is that OR assays will useful for identifying compounds that act as mosquito attractants, repellents, or blockers of olfactory behavior, providing novel technologies for disease vector control and suppression. As this strategy may be widely applicable to the control of many different insect species, an immediate goal of this project is to establish the validity of using OR-based screening to identify compounds for pest management.