EXCEED THE SPACE PROVIDED. To obtain a better understanding of the olfactory processes that allow mosquitoes to identify human hosts, a molecular study has been performed to identify and characterize molecules in the olfactory signaling pathway of the African malaria vector Anopheles gambiae. Using eDNA libraries from antennae of females and males, a collection of cDNAs encoding odorant binding proteins (OBPs) and other antennal proteins has been isolated and characterized. Their spatial and temporal gene expression in A. gambiae antennae using RNA and antibody probes will be determined, and the search for gender-specific expression of antennal genes will be continued. Concentrating on chemicals that have previously been shown to be attractants for female mosquitoes and also elicit an electrophysiological response, in vitro binding assays will be performed to study the interaction of specific odor molecules with mosquito OBP proteins. To investigate if altered expression of specific OBPs in antennae causes detectable behavioral and electrophysiological changes, transgenic mosquitoes will be generated that express RNAi against specific OBPs under the control of strong OBP promoters in their antennae. Suppression of OBP expression will be determined and the modified mosquitoes will be tested in wind tunnel experiments for behavioral changes in response to odorants, and for electrophysiological changes by single sensilla recordings. These studies will ultimately allow the development of better methods to interfere with the mosquito-host interaction and reduce transmission of the malaria parasite. PERFORMANCE SITE ========================================Section End===========================================
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