The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to digitize the human sense of smell and develop a platform to create "humanized mice" that that express any human odorant sensor in the nose of a mouse. Tools have been developed to determine the unique odor codes for each individual odor mixture that exists today ranging from the fragrances in a perfumer's palette to the Chardonnay in your wine cellar. Such an olfactory code will allow flavor and fragrance companies to predict the "smell" of certain odor mixtures, and to engineer new compounds in a rational and more streamlined manner. This technology will have a significant commercial impact on existing consumer products, including food, personal hygiene, household products, and perfumes, by offering a solution to more efficiently design pleasing scents and flavors or to formulate compounds that block repulsive odors. In addition, the proposed chemical detector platform under development to generate this olfactory code has additional applications as a biosensor. It may be used to generate disease-specific chemosignatures identified in bodily fluids like urine, sweat or blood, which may have application in clinical diagnostics and biomarker discovery.
This SBIR Phase I project proposes to use human odor sensors produced in their native environment, an olfactory sensory neuron, and develop an ex vivo biochemical assay to screen for odor sensor activation in a quantitative way. Since human odor sensors (odorant receptors) have proven to be exceptionally difficult to express in vitro, high-throughput screening of odorants using conventional pharmaceutical methods have not been possible to date. As such, only 10% of all human odorant sensors have been linked to their single odor. The preliminary data show that the in vivo expression of human odor sensors in mouse olfactory sensory neurons are functional. The objective of this project is to show that in vivo expressed odor sensors, when removed from their biological model system, maintain their functionality (i.e., ex vivo). A secondary objective is to demonstrate that several types of odor receptors, each with an accepted odor profile, will respond as predicted when analyzed ex vivo using a biochemical assay measuring direct activation of odorant receptors. Successful assay development will allow the generation of a viable platform that may be expanded with additional odor receptors to further decode human olfaction.
