Josefina Del Mármol

2022 Regional Award Winner — Post-Doc

Current Position:
Assistant Professor

Institution:
Harvard Medical School (previously, The Rockefeller University)

Discipline:
Molecular & Cellular Biology

Recognized for: Providing the first, structural snapshot of odor detection by an olfactory receptor (OR) from any species at the near atomic-level. At the molecular level, odors are composed of combinations of millions of chemically diverse compounds that animals must sense with only tens or hundreds of ORs. Through the use of cryo-electron microscopy, molecular biologist Josefina del Mármol, PhD, determined the atomic structure of an insect OR and how multiple odorants, including the insect repellent DEET, interact with it in a structural and biochemical fashion. del Mármol’s discoveries provided the first conclusive evidence that DEET targets insect ORs and supports the hypothesis that DEET ‘scrambles’ the olfactory signal to ‘confuse’ mosquitos.

Areas of Research Interest and Expertise: Olfactory Receptors, Structural Biology, Mosquitos, Odorants, DEET

Previous Positions:

Licenciatura, Universidad de Buenos Aires, Argentina (Advisor: Roberto Etchenique)
PhD, The Rockefeller University (Advisor: Roderick MacKinnon)
Postdoctoral Scholar, University of California, Berkeley (Advisor: Steve Brohawn)
Postdoctoral Associate, The Rockefeller University (Advisor: Vanessa Ruta)

Research Summary:

At the molecular level, odors are composed of millions of chemically diverse odorant compounds that animals must sense with only tens or hundreds of olfactory receptors (ORs). ORs were discovered over 20 years ago, but the structural and chemical interactions of how ORs can detect such chemical diversity has remained elusive. Molecular biologist Josefina del Mármol, PhD, is the first to demonstrate how ORs detect odorant chemical diversity. Through the use of cryo-electron microscopy, del Mármol determined the atomic structure of an insect OR and when bound to either the odorant eugenol or the insect repellent DEET. Her study provides the first structural snapshot of odorant-receptor odor detection by an OR in any species.

del Mármol also incorporated electro-physiological measures to determine how dozens of odorants, including eugenol and DEET, activate the ORs. Despite the fact that these odorants were structurally and chemically distinct, all of them were able to activate the same OR. By synthesizing the structure of this OR and the biochemistry of the dozens of odorants, del Mármol brilliantly created a mutant OR whereby DEET could no longer activate it. For decades scientists believed that DEET interacted with the mosquito OR, but del Mármol was the first to provide conclusive evidence that insect ORs are a molecular target of DEET and could act by ‘scrambling’ the olfactory signal and ‘confuse’ the mosquito.

By combining the structural insights of ORs with pharmacological screens, del Mármol aims to develop targeted insect repellents that could directly impact human health by curbing the spread of deadly mosquito-borne diseases such as malaria, Zika virus, and Chikungunya. 

This recognition is an outstanding vote of confidence as I start my independent career. It reinforces my commitment to continue working on unraveling fundamental mechanisms of sensory neurobiology and mentoring the next generation of scientists.

Key Publications:

1. del Mármol, M.A. Yedlin, V. Ruta. The structural basis of odorant recognition in insect olfactory receptors. Nature. 2021.
2. J.A. Butterwick. J. del Mármol, K.H. Kim, M.A. Kahlson, J.A. Rogow, T. Waltz, V. Ruta. Cryo-EM structure of the insect olfactory receptor Orco. Nature. 2018

Other Honors:

In the Media:

Quanta Magazine – Secret workings of smell receptors revealed for the first time

News Atlas – Science of smell: The first molecular images of odor receptors at work

Popsci – We have now seen our sense of smell in action

Trends in Biochemical Sciences – Spotlight: Seeing smell: the structural underpinnings of insect olfaction

Nature – News and Views: Insights into a receptor that lets insects sense scents

Servicio de Información y Noticias Científicas, Gobierno de España – Primeras imágenes moleculares de un receptor olfativo en funcionamiento

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