Odorant Receptor Expression and Sensitivity to Odorants

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DESCRIPTION (provided by applicant): The application proposes to allow an investigator experienced in the molecular biology of the olfactory epithelium to cross the gap from his expertise in microarray-based genomics to more computationally challenging next generation sequencing approaches. The plan includes: (1) training in R programming to allow the investigator take advantage of flexible analysis methods for ChIP-seq and RNA-seq techniques, (2) mentored pilot experiments in both of these approaches, and (3) mentored analyses of the data. The pilot studies take advantage of a unique resource that allows purification of olfactory neurons expressing subsets of odorant receptors to work toward testing two fundamental hypotheses about odorant receptors. (1) Active chromatin modifications (which can only be detected by enrichment for neurons expressing an odorant receptor) are critical for the tightly regulated expression of odorant receptors. Active chromatin modifications will be measured by ChIP-seq. The exquisitely specific control of odorant receptor expression is perhaps the greatest remaining mystery about the function of olfactory sensory neurons. (2) Odorants activate sets of odorant receptors that may overlap but must have at least one distinct member if the odorants can be discriminated. Enrichment for olfactory sensory neurons marked by expression of GFP from an activity-dependent gene locus will allow RNA-seq methods to identify sets of odorant receptors activated by specific odorants. Understanding the fundamental question of how hundreds of odorant receptors allow the detection and discrimination of thousands of odorant chemicals should help explain some causes of hyposmia and anosmia; and should allow the future development of odorant agonists and antagonists that could be used to improve the quality of human life.