Odorant Receptor Expression and Sensitivity to Odorants

The application proposes to allow an investigator experienced in the molecular biology of the olfactory epithelium to cross the gap between microarray-based genomics to more computationally challenging approaches that generate next generation sequence data. 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) followed by mentored pilot experiments in both of these approaches and mentored data analyses of the data. The pilot studies take advantage of a unique resource that allows purification of olfactory neurons expressing subsets of odorant receptors. The pilot studies work toward testing two related, fundamental hypotheses about odorant receptors: (1) active chromatin modification is critical for the tightly regulated expression of odorant receptors, and (2) purification of olfactory sensory neurons marked by expression of an activity-dependent gene will allow RNA-seq methods to identify odorant receptors activated by specific odorants. The exquisitely specific control of odorant receptor expression is perhaps the greatest remaining mystery about the function of olfactory sensory neurons. Similarly, how the hundreds of odorant receptors allow the detection and discrimination of thousands of odorant chemicals is a critical question for odor coding, causes of hyposmia/anosmia and the future development of volatile chemicals that could be used to improve the quality of human life.