AChemS Career Networking Seminar Series

MARCH 2021

Josephina del Mármol, PhD and Richard Gerkin, PhD
Natural odors are composed of hundreds of different molecules that share no obvious chemical or structural features other than those required for reaching receptors. The logic that governs how olfactory systems detect and interpret diverse chemicals remains enigmatic. Dr. del Marmol and Dr. Gerkin work to understand how odorant stimuli are encoded by olfactory systems. Using perceptual and behavioral data, electrophysiology, and cryo-electron microscopy spanning humans, mice, and insects, they seek to understand the molecular basis of odor-receptor interactions and their transduction into olfactory perception.

"Structural principles of odorant recognition in insect olfactory receptors." by Josephina del Mármol, PhD

To detect and discriminate the vast chemical world, animals rely on olfactory receptors (ORs) with broad receptive fields that can recognize a wide variety of different odorants. The molecular logic that determines an OR’s receptive field has until now remained elusive, due to steep technical challenges surrounding the structural characterization of OR-odorant interactions. Here, we use cryo-electron microscopy to elucidate the atomic structure of an insect OR in complex with two ligands, the odorant eugenol and the insect repellent DEET. These structures, combined with functional studies of receptor tuning, shed light on the molecular logic of promiscuous odorant recognition that ultimately endow the olfactory system with its immense discriminatory capacity.

"Parsing Sage, Rosemary, and Thyme" by Richard Gerkin, PhD

Color and pitch perception are largely both predictable and describable from the characteristics of physical stimuli: the wavelengths of light and sound waves, respectively. By contrast, the prediction and description of olfactory percepts from odorous stimuli (volatile molecules) is much more challenging. No intuitive set of molecular features is up to the task. I will describe a few successful approaches to “feature engineering” of odorant molecules and what they reveal about the structure of olfactory perceptual space and our ability to predict the odors of novel molecules. I will also highlight the limitations of this approach, where structural data alone is inadequate to the task of accounting for odor perception and behavior.