Chemosensory responses are critical components that direct several essential behaviors of insects that are vectors for pathogens responsible for many important human diseases. In particular, olfaction plays a major role in host seeking and selection behavior of blood-feeding female mosquitoes and as such constitutes a critical component of the mosquito's ability to transmit diseases such as malaria, dengue, yellow fever and West Nile Nile virus encephalitis. Within this context, I have undertaken a molecular examination of several elements of the olfactory signal transduction cascade in the principal African malaria vector mosquito Anopheles gambiae sensu stricto, where a significant preference for human hosts (anthropophily) underlies its inherent ability to transmit human malaria. An increased understanding of olfactory mechanisms and their underlying chemical cues in this system may provide insight in the processes of insect behavioral responses in general and vector disease transmission in particular. Moreover, this study would likely be instrumental in the development of novel mosquito control strategies targeted against this broad family of disease vectors, as well as other insects that pose considerable medical and economic threats through their ability to transmit disease and to act as agricultural pests. The objectives of this proposal complements ongoing studies in the laboratory of olfactory arrestins in A.gambiae and focus on an examination of a family of candidate odorant receptor proteins in A. gambiae (AgORs) that has recently been identified by this laboratory. Thus far, we have identified 44 candidate AgORs and have performed an initial characterization of a small subset of this gene family. While the exact number of potential AgORs remain to be established in A. gambiae, we proposed to begin a systematic analysis of this gene family by completing several studies focusing on their expression in the mosquito. Initially, in order to establish a strategic plan for future studies, we will employ a variety of molecular approaches to identify AgOR family members that exhibt sex-specific expression patterns. These AgORs will form our primary focus group for subsequent characterization of the developmental, spatial and temporal expression pattems of AgORs. In addition, in an extension of initial studies that specifically targets AgOR's role in the olfactory processes that underlie disease transmission, will we propose to conduct a series of detailed experiments to examine the temporal kinetics of AgOR expression in response to blood feeding.
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