Biophysical Society Bulletin | September 2024

Biophysicist in Profile

Emmanuel Margeat Area of Research Single-molecule fluorescence to study the structure and dynamics of membrane proteins

Institution Centre de Biologie Structurale, Montpellier, France

At-a-Glance

Emmanuel Margeat, Group Leader at the Centre de Biologie Structurale in France, was drawn to sci ence from an early age and has built a successful career in large part by embracing collaboration and new techniques—or new applications of existing techniques. He believes in the importance of giving back to the biophysics community, currently serving as inaugural Chair of the Biophysical Society’s newly established Committee on Sustainability.

Emmanuel Margeat

As far back as he can recall, Emmanuel Margeat was fascinated by science. As a child growing up in the small town of Tarbes, France, close to the Spanish border, he read books about as tronomy, geology, and computer science in his spare time. “I was probably the first kid in my hometown to have a personal computer—with 4K memory, running on tapes—because my father was a TV reseller and saw the opportunity to sell the first computers in his store,” he remembers. There was no university in Margeat’s hometown, so at age 17 he moved to Toulouse, France to pursue higher education at the University Paul Sabatier. He had trouble deciding wheth er to study chemistry, astrophysics, or computer sciences, eventually settling on physical chemistry. At the end of his undergraduate years, he was not sure what his next steps would be. He shares, “I was hesitant on what to do next, but by chance, I trained in a lab that was doing some biology. I discovered that my skills in physical chemistry—especially in spectroscopy and crystallography—could be useful to study biological processes at the molecular level. I borrowed a cou ple of books on structural biology at the library. A few months later, I started a graduate program at the University of Montpellier in Structural Biology. There, a new lab called the “Centre de Biologie Structurale” was being set up. I started working with atomic force microscopy and fluorescence and met Catherine Royer , the future president of the Biophysical Society, who had just moved to set up her group in France. I became her first PhD student in France.” He attended his first BPS Annual Meeting in 2000 as a PhD student, which was an opportunity to make connections and get to know people. He shares, “I remember finishing the poster session totally exhausted, having talked for two hours non-stop. It gave me confidence in my work and convinced me to look for a postdoc position later in the United States, and the science I saw started fueling my interest for sin gle-molecule experiments.”

Margeat notes, “During my PhD, thanks to the connections my adviser had in the United States, I had the chance to travel to the United States to spend a couple of weeks at the Laboratory for Fluorescence Dynamics in Urbana to work with Enrico Gratton and his group. We did FCS [fluorescence cor relation spectroscopy] experiments on estrogen receptor, the protein I was working on during my PhD.” He explains, “It was my first experience with research in the United States and with single-molecule microscopy as well. I discovered that a microscope could not only produce beautiful images, but also provide quantitative information about a biological system as well. It pushed me to look for a postdoctoral position in the United States, and preferably in the field of single-molecule biophysics, which was blooming at the time.” He joined the lab of Shimon Weiss at Lawrence Berkeley National Laboratory in Berkeley, CA, which relocated to the University of California Los Angeles shortly thereafter. He says, “I was working on a collaborative project with Richard Ebright from Rutgers University that aimed originally at look ing at DNA rotation during transcription using single-molecule fluorescence polarization. That proved extremely challenging, and finally I learned to do single-molecule FRET [Förster-res onance energy transfer] on this system. Together with Achilles Kapanidis , who was a postdoc on the RNAP [RNA polymerase] project as well at the time, and other talented people in the group, we joined forces and managed to make a decisive con tribution to understanding the mechanisms of transcription initiation.” After his postdoc, Margeat returned to France and a Centre National de la Recherche Scientifique research position, with the idea of establishing a group applying single-molecule FRET to biological systems. He explains, “I started a couple of projects related to transcription termination, focusing on transcription antiterminators, and the helicase Rho. But I wanted to bring the technologies I had in hand toward new

September 2024

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