Emmanuel Margeat, Group Leader at the Centre de Biologie Structurale in France, was drawn to science 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.
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 astronomy, 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 whether 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 couple 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 single-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 correlation 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 looking at DNA rotation during transcription using single-molecule fluorescence polarization. That proved extremely challenging, and finally I learned to do single-molecule FRET [Förster-resonance 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 contribution 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 biological systems, and preferably toward systems that can be handled and imaged more easily in live cells. I therefore started to work on membrane proteins and started new collaborations: first within my institute, with Pierre Emmanuel Milhiet, with whom we pioneered single-particle tracking experiments on tetraspanins; and then with Jean Philippe Pin across the street and Claus Seidel in Dusseldorf, Germany, with whom we published the first study of the structural dynamics of a G-protein coupled receptor using single-molecule FRET.”
Now, Margeat is a group leader at the Centre de Biologie Structurale, where he started his career. In France, a research group typically involves several senior researchers with independent, but interrelated research topics. He explains, “The group I co-supervise with Pierre Emmanuel Milhiet is called “Integrated biophysics of membranes” and comprises seven senior researchers. As the name says, we integrate several biophysical approaches toward the study of membranes and membrane proteins, such as single-molecule fluorescence of course, but also atomic force microscopy, NMR [nuclear magnetic resonance], DNA origami, and cell biology. On my side, our most recent developments involve the use of unnatural amino acids, click chemistry, and multicolor FRET to study molecular systems of increasing complexity, such as metabotropic glutamate receptors heterodimers. In addition, in January 2024 I became director of the Centre de Biologie Structurale, which gathers around 10 research groups and 30 PIs [principal investigators] around structural biology, biophysics, and synthetic biology.”
The biggest career challenge for Margeat has been to compete at the highest level with research groups from other countries who, from his point of view, “seem to benefit from unlimited funding and the capacity to attract an extremely skilled workforce. To face this challenge and stay competitive, I chose first to identify a niche for which my skills could give me a competitive edge. This was another argument to start working on membrane proteins, which require skills in sample preparation that were not necessarily mastered by the groups performing single-molecule fluorescence at the time, which were traditionally run by physicists. Second, I relied on what the French system has always promoted, i.e., collaborating and joining forces with other PIs in my institute and beyond.”
In recent years, Margeat has been active in various leadership roles within BPS, including as a member of the Public Affairs Committee and Council. He says, “This has given me the opportunity to meet with my peers, who I admire scientifically and who share my vision of the importance of giving some of our time and energy to run scientific organizations such as BPS, as public service. The Biophysical Society allows us collectively to be stronger to promote our science, but also to carry a credible and impactful voice when talking to decision makers and the general public. In addition, as Chair of the newly created Committee on Sustainability, I find urgent and vital that we all think about some issues, like the way we do science and plan experiments, our topics of research, and the way we communicate and travel. I think we should try to align our professional practices with the objectives of sustainable development in general and take into account environmental issues in particular.”
Outside of his research and service commitments, Margeat has in recent years developed a passion for astrophotography. He says, “I realized how easy it is to capture striking images of galaxies, star clusters, nebulae, or planets, with relatively limited equipment that you can have in your backyard—even if you live in a light-polluted area. The concepts and techniques of astrophotography are really connected to those I use every day in the lab, trying to image single molecules in my microscopes: it is all about PSF [point spread function], signal to noise, and trying to catch the maximum number of photons!”