Genetic and Molecular Analysis of Olfaction

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): The long-term goal of this project is to reveal the mechanisms by which odors are encoded, and to elucidate basic principles of the organization of the cells that encode them. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows powerful molecular genetic analysis of olfactory genes as well as physiological and behavioral analysis of olfactory function. The results may have major implications for the control of insects that transmit disease. The project focuses on a large family of Odorant binding proteins (Obps) that are remarkable in their number, diversity, and abundance. Despite their prominence, their role in the coding of odors is poorly understood. The first aim is to complete a map of the Drosophila antenna, in which all of the abundant Obps are mapped to the sensory hairs, or sensilla, in which odors are detected and encoded. This aim is designed to uncover organizational principles of a model olfactory organ and to lay a foundation for an incisive analysis of Obp function. The Obps will also be mapped to cell types with a view to testing specific hypotheses about the logic of their function. The second aim proposes a strategic analysis of the role of an Obp in odor coding. The Obp-to-sensillum mapping has already identified a sensillum type that contains a single abundant Obp. The proposal capitalizes on this opportunity to examine the effects of depleting the sensillum of its sole abundant Obp. The analysis is designed to test hypotheses about the role of Obps in coding odor stimuli that vary in their temporal dynamics, identity and intensity. As a byproduct, the analysis should reveal new information about odor coding of stimuli that are common in nature but surprisingly understudied. The aim could also lead to the establishment of a new empty sensillum system that would allow systematic analysis of Obps in a powerful way. The third aim examines an unusual Obp with unique expression that is exceptionally well-conserved. Its localization suggests that it could act in the response to insect repellents such as DEET. The analysis is designed to characterize the expression of this Obp in detail and to test the hypothesis that its function is required for normal repulsion responses. A successful outcome could lead to new understanding of the mechanism of action of insect repellents and could suggest new means of insect control Diseases carried by insects afflict hundreds of millions of people each year, and these insects detect and locate their human hosts largely through olfaction. Advances in the understanding of olfaction may lead to new means of controlling these insect vectors of human disease. In particular, new insight into the molecular and cellular mechanisms by which insects respond to repellents may lead to the development of a new generation of insect repellents, with implications for the control of insect vectors and the diseases they transmit.