This project uses a new in vivo assay that allows the identification of the odorant receptors activated in live mice by any odor, making it possible to identify in one experiment many receptors activated by the odor. This accelerates the identification of receptors sensitive to any odor and when combined with in vitro assays for the function of individual odorant receptors, allows testing of hypotheses about the sets of receptors activated by odorants and odor mixtures.
The first aim targets a specific region of the broad universe of odorants, testing whether the overlap in sets of receptors responsive to these odorants depends on their structural similarity.
The second aim tests hypotheses about the possible interactions between odorants at odorant receptors. It begins with pairs of odorants that are known or suspected of interacting, mostly by the ability of one odorant to block activation of one or more receptors by another odorant. It then moves on to testing more complex mixtures, seeking to identify interactive effects between odorants at receptors - effects that are fundamental to the characteristic sensation of the odor and the discrimination of one odor from another. In addition to improving our understanding of the mechanisms of odor perception, these experiments provide knowledge expected to facilitate the development of more sophisticated ways of manipulating odor environments to benefit the quality of human life.
The array of sensors for odors is composed of hundreds of distinct odorant receptors in most mammals, but which of these receptors respond to the thousands of odor chemicals is virtually unknown, making it difficult to understand how we detect and discriminate odors. This project uses a newly developed, novel strategy to identify the sets of receptors responsive to any odor we choose to test. This information will help us understand how we discriminate odors, as well as lay the groundwork for developing pharmacological agents for altering odor detection, a direction that should lead to improved flavors and fragrances, blockers of noxious smells, and even improved pest control.
|Wang, Qiang; Titlow, William B; McClintock, Declan A et al. (2017) Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium. Chem Senses 42:611-624|
|Zhang, Guangfan; Titlow, William B; Biecker, Stephanie M et al. (2016) Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons. eNeuro 3:|