BRAIN EAGER: Solving the Code of Olfaction Using Nano-Robot Switchable Odorants

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The sense of small (olfaction) holds in it a major mystery: No scientist or perfumer can look at the structure of a novel molecule and predict its odor or molecular structure. This project aims to develop molecules that bind to individual olfactory receptors in the nose and thereby help solve the code by which odors result in odor perception. The proposed approach has broad implications and applications: It may pave the path towards the introduction of odor into everyday devices. The idea of odor-emitting televisions, computer game boxes, cell-phones, etc, has existed for some time. However, this goal remains unattained, mostly for "simple" technical reasons: Even if one successfully generates an odor-emitting device, what does one then do with the emitted odor? For example, a car-racing computer game may emit the smell of burning rubber tires, but how does one then evacuate the smell of burning rubber from the room? Moreover, given that odors linger, how can one rapidly switch from one odor to the next? The technology proposed here may solve these problems because it will entail particles that are odorless, yet take on a given odor as a function of rapidly-switchable externally applied fields. If successful, the proposed mechanism will drive a revolution of odor devices. Further, the "switchable chemical" approach will be extendable to other receptors in the brain, and can be applied towards asking basic questions concerning emotion, sensorimotor-coordination, memory and learning, as well as developing potential novel therapies for diseases associated with receptor signaling failure. To develop a path towards solving the combinatorial code of olfaction, the Bachelet lab will design DNA strands called aptamers that assume a 3D structure that will specifically bind to a single type of olfactory receptor and induce signal transduction. These DNA-based "artificial odorants" will be tagged with a nanoparticle that changes its conformation in response to an external electromagnetic field. The product will be artificial odorants that are externally switchable in vivo. The Matsunami lab will use tissue culture cells expressing olfactory receptors to validate the function and selectivity of these switchable nano-robot odorants. The Sobel lab will then apply these artificial odorants to the human olfactory system, and measure perception and neural activity following switching the artificial odor on and off. This three-level approach will allow closure of the loop from receptor to perception, and potentially answer in this way what remains a fundamental question in olfaction.