ANALYSIS OF ODORANT RECEPTOR GENES

Yale University, New Haven CT

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Abstract

DESCRIPTION (From the Applicant's Abstract): This project is designed to reveal basic principles of olfactory system function and development, through a detailed analysis of the recently discovered DOR family of odorant receptor genes. The proposal addresses fundamental issues of receptor function, taking advantage of the strengths of Drosophila as an experimental system. Olfaction is an ancient sensory modality, and many principles of olfactory function and organization are well conserved among invertebrates and vertebrates. Moreover, understanding of insect olfaction may be useful in controlling insect vectors of human disease that find their human hosts or their mates through olfactory cues. The proposal aims first to identify and classify all members of the DOR gene family, including highly divergent members. Extant mutations affecting DOR genes will be sought. The distribution of receptors in the mature olfactory system will be addressed in two ways. First, the recent isolation of an antibody against a DOR protein allows a high-resolution analysis of receptor localization in the olfactory system. Results showing that the DOR22A.2 protein is present in the cavities of olfactory sensilla, as expected of an odorant receptor localized to dendrites, will be confirmed and extended by immunoelectron microscopy and with antibodies against additional DOR proteins. Second, the number of receptors per neuron will be investigated by double-label in situ hybridization. A developmental analysis of receptor expression is proposed. The developmental profiles of all DOR genes will be analyzed, with a view to determining how many genes are expressed early in development, as is DOR22A.2. Preliminary immunohistochemical results indicating that the DOR22A.2 receptor is present on the axons of olfactory receptor neurons will be confirmed and extended. A genetic analysis of selected DOR genes is proposed to test the hypothesis that they encode odorant receptors. DOR gene function will be altered through overexpression and by loss-of-function mutations. These experiments may identify a ligand for a DOR protein. They may also provide functional evidence regarding the number of receptors expressed per neurons, and the possibility of developmental roles for receptors.