Winner of the 2023 Irène Joliot-Curie Award in the “Young Scientist” category, this chemist succeeded in reproducing the first experimental structure of a human olfactory receptor.
Claire de March is a scientist with intuition. In November 2023, along with four other laureates, she received the Irène Joliot-Curie Award of the Academy of Sciences as “Young Scientist of the Year”. A few months earlier, with an international team, she managed to obtain the first experimental structure of a human olfactory receptor. So far, scientists’ work has been based on structures obtained from vision receptors. A hypothesis that is certainly useful, but insufficient to encompass the complexity of the interactions between our neural system and the countless smells that inhabit our planet. ” Before this discovery, we knew nothing about these receptors. It was the researcher’s dream to be able to publish this discovery “, she rejoices.
A passion for smells, flavors and tastes
An award that comes at a crucial time, just three years later the global epidemic of Covid-19 that highlighted taste and smell disorders, and we still haven’t been able to solve some of the most fundamental questions about the mechanisms of smell. It also comes after years of hard work, although Claire de March has difficulty identifying a specific moment when her passion for her subject of study was born. ” Nothing predestined me to love science and embrace this careershe recalls. I had a very artistic childhood, my mother studied fine arts, my father studied electronics, and my grandmother was a cashier. The image of a scientist did not particularly attract me, but chemistry immediately spoke to me at school. What interests me is the complexity of mixtures and combinations. »
In her laboratory at ICSN, a young researcher is working on deciphering the mechanisms of smell.
She still remembers the time when, as a child, she cooked with her grandmother and chose ingredients to create recipes. ” The smells of vanilla and cake escaped from the oven. Smells are not memories that we often share with others. However, they remain important. » The researcher is sometimes still carried away by the scent of patchouli, which reminds her of the perfumes her mother wore when she was a child, or those ” which can be seen after the person leaves the room » as an olfactory signature.
Although we know that humans have almost 400 olfactory receptors in the nose, we have not been able to reproduce the structure of any of these receptors at the atomic level. I could only rely on hypotheses for my work.
This pronounced taste for compositions led her to naturally move towards a career as a chemist from high school. Claire de March is moving towards a technology baccalaureate, but wants to go further in her studies. After a long journey on which she tried ” escalate the university pyramid again “, she passed the competitive exam of the Versailles school for perfumers and aromatists: ” I did not have the necessary diploma to apply for the competition. I had to hang the wagons. But I was fortunate to encounter very kind teachers who allowed me to progress quickly and get up to speed. “, she admits.
After the competition was over, she joined an apprenticeship with the industrialist Bel, in the food department. Joining this sector was an accepted choice at an age when students were working on courses in perfumery. ” I never wanted my blends to smell good. I preferred the complexity of flavors and tastes », assures the one who takes as an example a truffle, which we would not imagine wearing as a perfume, but whose taste we still appreciate.
Claire de March is completing her MSc and then continuing her journey with a thesis in computational chemistry at the University of Nice. She hopes then practically recreate the human nose but he faces a big challenge: ” Although we know that humans have almost 400 olfactory receptors in the nose, we have not been able to reproduce the structure of any of these receptors at the atomic level. I could only rely on hypotheses for my work “. Then she turned to biologists and contacted Hiroaki Matsunami from Duke University in North Carolina, who had conducted the first in vivo tests of olfactory receptors in mice. A structuring meeting in his professional career.
In the origin of the first artificially reproduced human olfactory receptor
After defending her thesis, she went to the USA to join Hiroaki Matsunami’s team. He will remain across the Atlantic for seven years. With this mentor, Claire de March learns to channel her boundless energy, but also her worries as a young researcher. He is gradually gaining confidence. ” I learned that I can’t know everything without questioning myself and that as a scientist I have the right to make mistakes. “. Learning that will benefit him: ” When she arrived in December 2022, Claire joined an old and established team. She accepted this challenge brilliantly », welcomes Carine Van Heijenoort, deputy director of the CNRS Institute for the Chemistry of Natural Substances (ICSN), in Gif-sur-Yvette, who describes it as “ a caring, direct and open-to-discuss associate “. ” She is someone who is inspiring in the way she approaches things. She shows such enthusiasm that it builds momentum », adds Boris Vauzeilles, director of the institute.
The first structure of a human olfactory receptor. The odor receptor protein, OR51E2 (purple), which the researcher identified, is activated by the smell of propionic acid (a white and red molecule), one of the compounds that give cheese its distinctive smell.
This determination also allowed him to artificially reproduce the human olfactory receptor for the first time. Similar to the photosensitive cells in our eyes that respond to wavelengths corresponding to different colors, the olfactory receptor can actually be sensitive to a number of chemical functions and recognize a number of odor molecules; but the combinations are much more numerous for odors than for wavelengths.
It’s a bit like a grand piano: the smell is like a musical chord. This tuning can be achieved using several receivers which can be the keys of the instrument. The key in turn can be included in different musical chords.
Indeed, an odor molecule can in turn activate several receptors, which makes it possible to distinguish a multitude of odors, but makes Claire de March’s exercise even more complicated. ” It’s a bit like a grand piano: the smell is like a musical chord. This tuning can be achieved using several receivers which can be the keys of the instrument. The key in turn can be included in different musical chords “, she describes. To compile this assessment, the researcher observed how the olfactory receptor OR51E2 reacts to contact with different chemical compounds, and then reproduced its behavior on a computer, at the molecular level.
This process could change our knowledge of how we respond to smells: it could explain why some people find a smell pleasant, while others are completely indifferent to it. It also paves the way for the creation of new fragrances in areas such as perfumery and the food industry. In addition, certain olfactory receptors are also involved in other biological processes such as the release of serotonin in the gut or even prostate cancer. ” Odor receptors are becoming new potential therapeutic targets, especially in anti-cancer treatments. We don’t tell ourselves we’re going to save the world by researching the sense of smell, but it just might happen eventually! », the researcher begins to daydream.
Regeneration and activation of ancestral receptors
Another of his scientific endeavors is that he was able to virtually recreate one of the olfactory receptors of the Denis man – an extinct species from the genus Homo who lived on Earth more than 30,000 years ago – from their DNA. ” I really like history and archeology so this research was unexpected. When I saw this receiver activated on my machine, it was a small miracle. I remember thinking that this receptor had not been activated by an odor molecule for tens of thousands of years! », wonders Claire de March. The chemist also managed to practically recreate the ancestral receptors of the first organisms that could detect odors with the aim, once again, of facilitating future research in the field of smell.
Claire de March managed to virtually recreate one of the olfactory receptors of the Denisovan man – an extinct species from the genus Homo who lived on Earth more than 30,000 years ago – from their DNA.
She was recently inspired by the scientific work of other colleagues: Vanessa Rute, an American neuroscientist who deals with the mechanisms of odor recognition in insects. ” Impressive works, with which I can easily identify », explains researcher or researcher Noam Sobel of the Weizmann Institute of Science in Israel, who seeks to elucidate the cerebral mechanisms of the human olfactory system and their key role in our social interactions and emotions.
In addition to being a successful scientist, Claire de March also advocates for a better integration of women into the world of research. Upon arrival, she joined ICSN’s Equality-Parity-Inclusion Unit. ” We are only at the beginning of changes and it is still difficult for women to continue their careers in science », laments the chemist. She complains that female scientists also have few role models to lean on. ” In the world of fragrance research, fortunately, we have a Nobel Prize winner, Linda Buck ! “, she greets. Claire de March’s talent may one day inspire a new generation of researchers. ♦
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