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w 16 | Profile cnrs I international magazine Biology Researcher Margaret Buckingham, a specialist in stem cells and in the formation of skeletal muscle and the heart, was awarded the 2013 CNRS Gold Medal. Margaret Buckingham At the Source of Cells BY Émilie Badin If she had not been a biologist, she might have been a painter, of the expressionist school perhaps. However, Margaret Buckingham devoted all her talent to research. She almost apologizes for not having done both, “but in life, you can’t do more than one thing well.” In her case, very well indeed. At 68, this CNRS emeritus research director and emeritus professor at the Pasteur Institute was awarded the 2013 CNRS Gold Medal, France’s highest scientific distinction. AGAINST ALL ODDS There is something very unpretentious about her, which puts you immediately at ease. Despite her prize, she has kept her feet on the ground. She insists that she did not expect it at all. “I was in the Eurostar on my way to a genetics meeting in Cambridge when my phone rang. When I heard ‘hello, this is Alain Fuchs, President of the CNRS,’ I wondered if I’d done something wrong! I’m very honored by this prestigious French prize.” Margaret Buckingham spent part of her childhood in the north east of Scotland. A place of harsh and majestic landscapes, featured on the photos on the walls of her study, a place where the weather, admittedly, is “impossible.” The daughter of a professor of philosophy specialized in Plato and Aristotle, the young Margaret had plenty of intellectual stimulation. Albeit not in science. “In my girls’ school, for lack of money, science wasn’t taught, or hardly,” she recounts. “Yet I remember the teacher who taught a bit of biology and who was happy to depart from the official curriculum to read us articles from Scientific American. Those were the days of the great discoveries about the genetic code. These articles immediately fascinated me and prompted me to study biology.” So much so that, at 18, when she sat the entrance examination for Oxford University, she was determined to do a degree in biochemistry. She went on to do a PhD on  histone  modification. She then left Oxford for Paris. “I wanted to go there,” she says. “First and foremost for the cutting-edge research into messenger RNA that was being done at the Pasteur Institute, which inspired us as undergraduates, and secondly because my artist grandfather had always dreamed of seeing Paris and the landscapes painted by the Impressionists. His dream never came true. I went instead, partly for him.” In 1971, François Gros, a prominent specialist in messenger RNA, took her into his lab as a postdoc. Since then, she continued to work in France and obtained dual nationality. The freedom to do the research that she thought was important encouraged her to stay in France. Recruited by the CNRS in 1975, she set up a small team within François Gros’s unit at the Pasteur Institute two years later. In 1987, she became head of the Molecular Genetics of Development Unit, a position she held until 2011. In 1992, she was appointed professor at the Pasteur Institute, where she was director of the Molecular Biology Department (1990-1994) and subsequently of the Department of Developmental Biology (2002-2006). PREDICTING CELL FUTURE “I chose developmental biology because I was—and still am—fascinated by this extraordinary phenomenon: a whole organism that develops from a single cell, the fertilized egg,” she explains. With her successive students and postdocs, she set out to understand how the first cells, which are all alike, acquire different cell fates. She first looked at how a so-called naive cell receives the signal to become a muscle cell in mammals. “We showed that, in the embryo in vivo, in the absence of the myogenic determination factor, Myf5, cells contribute to non-muscle tissues,” she explains. But she wanted to go further upstream, and understand how cells are gradually steered towards their final fate. In the early 2000s, she showed with her team that the transcription factor Pax3 is responsible for this regulation. In 2005, they demonstrated the role of a reserve of muscle stem cells that express Pax3 and also Pax7, present in the embryo and also in the adult where they are in close contact with the muscle fiber. “We showed that these so-called satellite cells, which are mobilized when the muscle is damaged, are responsible for muscle regeneration.” MEDICAL APPLICATIONS When asked which achievement she is most proud of, she mentions the regulation of muscle stem cell fate. But she also evokes congenital heart malformations histone. Nuclear alkaline proteins that participate in the packaging and structural ordering of DNA in the cell nucleus. “I chose developmental biology because I was fascinated by this extraordinary phenomenon: a whole organism that develops from a single cell.”


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