US-French Research Proposal: Collaborative Research: Predicting Odorant-dependent and Independent Olfactory Neuron Activation Based on Receptor

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Smell is a powerful sense that can trigger intense emotion, stereotyped behaviors and durable memories. The sense offers an extraordinary opportunity to connect atomic-level objects (odorant molecules and smell receptors in the nose) to neural responses. This project will predict which smell receptors in the nose are activated by a given odor. To accomplish this goal, the team of investigators will apply computational approaches to develop chemical structure-based receptor models and test these models using odor molecules interacting with olfactory receptors. The success of the project will enable the team to understand more precisely how the brain perceives the external environment. The results will also have widespread and diverse industrial applications, including rational design of new flavors and fragrances and development of new biosensors for detecting various chemicals. Furthermore, this project will make broader impacts in training and educating high school, undergraduate, and graduate students in various disciplines as well as in outreaching activities. The complexity of the odor molecules, the large number of the smell receptors and combinatorial activation of the receptors make understanding odor coding an enormous challenge. This collaborative proposal represents the first of its kind that combines computational approaches with experimental measurements at both the receptor and the neuron level. Affinity calculations between odorants and the receptors, as well as the receptors' activation, will be obtained by nanosecond-scale simulations. Atomic-level simulations, initially assessed by experiments, will predict which odors would activate the receptors of interest. Comparisons between experimental findings and computational predictions will lead to a comprehensive computational model that converges with experimental data. A companion project is being funded by the French National Research Agency (ANR).