Born in Paris to French parents, Seydoux had a somewhat nomadic childhood, living in France, Italy, and (briefly) in the United States, where her father, a biochemist, did his postdoctoral research. “I remember being in his lab, waiting for him to finish his work,” she recalls. Seydoux’s father died when she was 13, and several years later, her mother moved temporarily to Maine. Seydoux decided to attend college in the U.S., enrolling at the University of Maine. She chose biochemistry as her major, not, she says, because it had been her father’s field of study but because it presented less of a language barrier for her. “Science is a universal language, so it was easier to take physics than literature classes,” she notes with a laugh. Seydoux also knew that as a foreign student, her opportunities to work and earn money during the summers were limited—except if she worked as part of a science research program.
It was during one of those summer programs—at the Cold Spring Harbor Laboratory in New York—that Seydoux became fascinated with genetics. “I did my first genetic screen that summer, and it was so much fun,” she recalls. “You could let the organism speak to you. You didn’t have to go in with any preconceived notions of what you would find.”
After that summer, Seydoux knew she wanted to pursue genetics. She also wanted to stay on the East Coast. So, in 1986, she enrolled at Princeton University, eventually finding her way to the laboratory of molecular biologist Iva Greenwald. “She was looking for new people to fill up her lab,” says Seydoux. “She asked me if I wanted to look at C. elegans under the microscope, and as we did so, I saw a cell divide. That just blew me away. I thought, this is a wonderful organism to study. I did a rotation with her, and that was that.”
In Greenwald’s lab, Seydoux studied cell-to-cell interactions in C. elegans embryos. She demonstrated that the membrane-associated protein LIN-12 mediates signaling between cells by acting as a receptor, a finding that was confirmed for similar proteins (Notch family) discovered in other organisms including humans. She also made the unexpected finding that competition between cells to become “signaling” or “receiving” cells is an important mechanism to generate different cell types during animal development.
For her postdoctoral studies, Seydoux worked with molecular biologist (and future Nobel Prize laureate) Andrew Fire at the Carnegie Institution for Science in Washington, D.C. “We were trying to figure out when cells start to transcribe their own genes in the early embryo, but at that time there were a lot of technical hurdles,” she recalls. Then one day, after trying a new protocol provided by a colleague at the Carnegie Institution, Seydoux was able to overcome that research barrier. “The embryo only had four cells, and we could see that three of the cells were making their own RNA in their nuclei,” she recalls. “But one cell didn’t—and that was the precursor to the germline. That meant RNA transcription was happening in the somatic [non-reproductive] cells, but not in the germ cells.” This chance discovery is what led Seydoux to focus on germ cells and her eventual discovery that repression of transcription is essential for germ cell fate.
In 1995, Seydoux accepted a faculty position in the department of molecular biology and genetics at the Johns Hopkins University School of Medicine, where she has remained ever since. In the ensuing years, she has combined genetic biochemical, and cell biological approaches to make groundbreaking discoveries about how the germ line of C. elegans is established and how the fates of its germ cells are determined. In addition to demonstrating that specific transcriptional silencing prevents new germ cells from adopting somatic fates and that translational control governs germ cell specification, Seydoux has shown that this translational control is largely mediated by the three prime untranslated regions (3’ UTRs) of mRNAs and their interaction with Puf proteins. These findings have underscored the global importance of mRNA stability on gene expression. Seydoux and her team have also described how mRNAs important for germ cell development are recruited to P granules, dynamic compartments in germ cells that are not bound by membranes. Her lab has shown that P granule assembly and disassembly is controlled by tiny protein/RNA aggregates that adsorb to the surface of P granules, the first documented example of a biological “Pickering agent”. Through this work, scientists have developed a better understanding of how membrane-less compartments, sometimes referred to as biomolecular condensates, can be studied genetically.
Seydoux has received numerous awards and honors during her career, including membership in the National Academy of Sciences and the American Academy of Arts and Sciences. In 2001, she received a McArthur Fellowship. “That was really amazing,” she says. “It was like a warm hug from the scientific community. It also gave me confidence to continue taking risks in my research.” She is also an investigator of the Howard Hughes Medical Institute. Seydoux, who has two grown children, lives in Baltimore.