For 20 years, Déborah Bourc’his has been fascinated by the epigenetic mechanisms that affect the DNA of mammals, particularly during reproduction. Thanks to her discoveries, the researcher has just been awarded the Liliane-Bettencourt prize for life sciences.
As a child, Déborah Bourc’his had her own personal take on biology: in the forests of the Touraine area in France’s Loire valley, she used to enjoy looking for flints shaped by cavemen. She would also spend her days picking flowers and other plants, before carefully filing them in her herbarium. "I loved collecting things from the natural world”, she recalls. Four decades later, she has still not outgrown this childhood passion: in her lab at the institut Curie in Paris she is fascinated by the collection of the tens of thousands of genes contained in mammal DNA. "I thought I wanted to be a doctor”, explains the scientist. “But I became really interested in genetics at high school. The examples were very simple ones, but I was fascinated by the thought processes required to study the topic, along with this idea of transmission and heredity." Her father, a French teacher, and her mother, a hospital manager, were full of encouragement. "I was entering a very prestigious area, everyone was delighted."
At university, in the early 1990s, the young woman witnessed the beginnings of a small revolution. In the midst of all the usual terms employed when talking about genetics (DNA, genes, replication), a new concept emerged: methylation – i.e. the fact that DNA can undergo natural biochemical changes via the addition of methyl groups. The activity of the genes can be modified as a result, without the DNA sequence changing. This methylation can also be transmitted during cell divisions and even to subsequent generations. This revolution soon became known as epigenetics.
We didn’t really understand much about the mechanics, but it was clear that we needed to incorporate this new knowledge into what we already knew about the transmission of traits. I knew straight away that I wanted to work on DNA methylation
Few labs were interested in the subject at the time. In 1996, the young researcher joined Evani Viegas-Péquignot’s team at Necker hospital in Paris, to carry out a Ph.D. thesis on ICF syndrome, a rare genetic disease related to a constitutive methylation defect and combining immunodeficiency, chromosomal instability and facial abnormalities. While there, she identified DNMT3B methylation mutations. In 2000, the "budding methylation expert” set off for the USA. "Going to live in New York was a childhood dream of mine. My grandfather had worked there in the 1920s and I was always entranced by his stories. When I was 5 years old, he taught me how to whistle through my fingers for a yellow cab like they do there!" she laughs.
At the prestigious Columbia University, in its genetics and development department, she discovered during her post-doctorate work that sperm and eggs need special stimulation to acquire methylation of their DNA, via cofactor 3 DNMT3L. "It was a fabulous experience”, she recalls. It was there that I met Timothy Bestor, my mentor. Working alongside him was a great way to learn from example, as we discussed the concepts emerging from our research. We’re still very close today."
In 2009, after being recruited by Inserm as a researcher, another very exciting opportunity came along. The field of epigenetics was radically changed by the advent of large-scale mapping technologies. These make it possible to analyze all the epigenetic modifications of the DNA of the genome, as well as of histones 3 around which the DNA molecule is wrapped.
The institut Curie, with the support of the CNRS, Inserm and Pierre-et-Marie-Curie University, opened a new unit dedicated to genetics and developmental biology. "Edith Heard, who manages the unit, asked me to join it in order to form one of the teams focusing on epigenetic decisions and mammal reproduction", explains the researcher.
To start with; we were just four team leaders and we had to do everything until reinforcements arrived! It was a great opportunity to build a scientific identity. Today, there are more than a hundred of us working in the unit and ten teams.
Déborah Bourc’his’ team recently made two discoveries: the demonstration that the size of an individual in adulthood is determined from the very first days of development by the indelible methylation of a specific DNA sequence, then the unexpected identification of a new DNA methyltransferase – an enzyme that enables methylation –, dubbed DNMT3C and specialized in the methylation of spermatozoa and male fertility. In total, the researcher had therefore deciphered three of the five known methyltransferases (DNMT3B, DNMT3L and DNMT3C).
Asked about the widespread differences of opinion in the world of epigenetics, she readily opts to take the side of what she calls “the epigenetics police”. "Some might call me rigid, but I believe that this discipline needs to advance within a clearly defined framework: first and foremost, we must work to fully understand the basic mechanisms underpinning epigenetics. At present, we still have a long way to go. Others already prefer to talk about the influence of the environment on these epigenetic markers: for me, this tangent tarnishes what epigenetics really are, in other words, primarily normal development mechanisms, not something that will necessarily have a negative impact on an individual’s health", she explains.
Déborah Bourc’his is set to be kept pretty busy in the immediate future: in addition to being the young mother of a little boy, Merlin, she has just been awarded the Liliane-Bettencourt prize for life sciences. Worth some 300,000 euros, the prize is awarded to a researcher under the age of 45 recognized for the quality of their publications, their status as a reference in their field, a promising research project and, above all, remarkable personal qualities. It will enable the scientist to cover the salaries of post-doctoral researchers, but also to implement innovative approaches, rarely supported by funding agencies. "Good news of this magnitude is pretty unusual in the world of French research. I am extremely proud and honored to have been awarded this prize, especially as it’s the first time it has been given to a woman since 2009. The gender gap in research leadership positions is very real. Young women need to see examples of women who have combined a successful professional career with a fulfilled family and social life", concludes the researcher.
Find out more about Déborah Bourch'is
Déborah Bourc’his directs the Epigenetic decisions and mammal reproduction team (Inserm unit 934/CNRS/Institut Curie/Université Pierre-et-Marie-Curie, Developmental Biology and Genetics) at the Institut Curie in Paris.
- 1996-2000 Doctorate at Necker hospital in Paris
- 2000-2005 Post-doctorate at Columbia University in New York
- 2005-2009 Inserm research fellow at Paris-Diderot University in Paris
- 2009 Head of the Epigenetic decisions and mammal reproduction team, Developmental Biology and Genetics unit at the institut Curie in Paris
- 2017 Liliane-Bettencourt prize for life sciences