Functional Domains and Expression of Olfactory Receptors

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DESCRIPTION (provided by applicant): The mammalian olfactory epithelium does two remarkable things with its olfactory sensory neurons. These neurons detect odorants, translating the structure of volatile chemicals into a neural information code, and the epithelium can replace these neurons even if they are completely eliminated. These properties are of significant interest for both basic and applied neuroscience research. The goal of this project is to generate a finely detailed description of the phenotypes of the mature olfactory sensory neurons and their immediate progenitor cells, then use this description to predict critical steps in the molecular mechanisms that lead to the genesis of these neurons, their ability to detect certain odors, and their ability to survive in their exposed position. The first aim of this project combines a system-wide view of gene expression with our ability to purify certain cell types so that we can assign gene expression patterns and the biological processes they represent to their correct homes in the cells of the epithelium. The second aim takes advantage of predictions about genes whose products regulate the activity of other genes made by our preliminary data. We will test whether targeted knockout of six of these regulator genes, all expressed by immature olfactory sensory neurons, causes deficits in either the production of mature neurons or in critical functions of these neurons. The third aim is based on our belief that within the expression patterns we observe in olfactory sensory neurons are sets of genes responsible for survival of the neurons. We will use odor stimulation, which is known to enhance survival, to increase the activity of pro-survival genes (or suppress anti-survival genes) so that they can be detected. This project is an integrated approach to understanding the genes whose activity is important for generating the phenotype of mature olfactory sensory neurons and then maintaining these cells in the face of significant challenges.