Edith Heard, enthusiastic epigeneticist

                      Elphège Nora and Edith Heard in their office at Institut Curie

PSL:  What is epigenetics to you, and why did you choose this field?

Edith Heard: For me, epigenetics is first and foremost the discipline that connects the dots between genetics and developmental biology. That is how Conrad Waddington defined it in 1942. The concept has evolved in the interim, of course, with other components being added, such as the heritability of cellular memory (or how a decision made by a cell is passed down in a stable fashion to its child cells). I am a geneticist myself, and I went into developmental biology after writing a dissertation on genetic instability related to cancer in London. Through this work, I developed an interest in epigenetics, a factor suspected to be involved in the development of cancer, and in molecular bases, which had been studied very little. This led me to do my post-doc on an epigenetic process that takes place during embryogenesis in mammals, the deactivation of the X chromosome. That’s how I ended up as a postdoctoral fellow at Institut Pasteur, on the team of Philip Avner, a specialist in the field. In 2001, I was hired as a young team leader for the Nuclear Dynamics and Genome Plasticity unit directed by Geneviève Almouzni, another epigenetics specialist. From there, in 2008, I joined the new center devoted to developmental biology created by Daniel Louvard before becoming director of the Genetics and Developmental Biology unit. We now have 10 teams of scientists – and several of us are working on epigenetics (Déborah Bourc’his, Raphaël Margueron, Alena Shkumatava, etc.).

PSL: In your opinion, where does Institut Curie fit in with the world’s major epigenetics research centers?

EH: Institut Curie is recognized for its work in epigenetics thanks to all the teams teaching and working on the topic. Geneviève Almouzni’s involvement over the past years in developing European epigenetics networks (Epigénome, Epigenesys, etc.) has done a great deal to help build this recognition. More generally, France has an excellent network of epigeneticists in cities such as Montpellier and Lyon. There is also a high concentration of epigeneticists in Paris, particularly at PSL (Paris Sciences & Lettres). In addition to the Institut Curie teams I mentioned before, this also includes the work of Vincent Colot, Chris Bowler and Lionel Navarro at IBENS (Institut de Biologie de l’ENS), and Marie-Hélène Verhlac and Alain Prochiantz at Collège de France... I can’t list them all, but there are many people working in the field.

PSL: What advice would you give a student wanting to join your team?

Science is expensive, we are incredibly lucky to get to pursue this career, and in return it demands high standards and an unwavering attention to detail.

EH: Apart from an interest in epigenetics... I think it’s essential to understand the qualities of a good researcher, namely passion, a sense of duty, and high standards. Science is expensive, we are incredibly lucky to get to pursue this career, and in return you must have an unwavering attention to detail and a certain level of devotion. Even outside the laboratory, scientists are constantly mulling over their subject and nurturing their lines of questioning... So I think it’s essential for students to fully inhabit their subject. At the lab, we provide them with tools, resources, and supervision, but the research is their own, and it’s up to them to bring it to fruition. This teaching approach has produced results: some of the biggest discoveries by my team were made by students. Former students and post-docs have also gone out to form their own teams, develop their own projects, and make new discoveries: that’s wonderful, and we are so proud of them! In fact, I am currently in contact with the young researchers they have trained themselves, as though they were part of my team: it’s as though we are passing along an approach to science. Sort of like epigenetics! (laughs)
 

PSL: In your opinion, what are the major challenges facing future PhDs in epigenetics?

It takes only a few weeks to generate a mutated mouse, instead of 2 or 3 years like before. If ever there were a time when the effects of science were measurable, it’s now!

EH:There are so many--we’re just starting out! The first that springs to mind is exploring the way epigenetic changes can be reversed. This would involve a much more molecular-level understanding of the basis of epigenetics, i.e. chemical and not just biological, to determine how to interfere with, change, and modulate the epigenetic process. On my team, chemist Lucile Marion-Poll (a neurobiologist) is already working on these questions by looking at how gene expression contributes to neurodegenerative diseases like Alzheimer’s or Parkinson’s.
Another challenge: exploring the organization of genomes. Six years ago, through a collaboration with the US laboratory of Job Dekker, who invented a technique to “capture” interactions between different parts of the genome, we discovered that the genome is organized into topologically associating domains, or TADs. You can imagine them as a series of “balls” each encompassing hundreds of kilobases, which partition genomes and could play an important role in regulating genes in development. Based on these discoveries, we now need to understand the exact nature of these domains. Currently, two of my former colleagues are working on a different angle of the same problem: Elphège Nora (a former student on my team), who worked with us on the discovery, is looking at the molecular bases of this organization; Luca Giorgetti, a physicist and biologist who did her post-doc on my team, is modeling it to understand its physical bases and make predictions.
One final challenge: taking advantage of the potential for Biology research offered by new tools and sets of data collected. For a long time, there were a few essential, fundamental rules (the theory of evolution, the double helix of DNA, the genetic code, etc.) and many variables. Today, tools for genetic or epigenetic editing using CRISPR/Cas9, high throughput sequencing at the cellular level, molecular imaging, time measurement and quantifications are all revolutionizing the field. I am convinced that this mass of collected data will enable the emergence of new rules on a precise, quantitative basis. It’s exciting, and it’s moving so fast! These days, it only takes a few weeks to test a hypothesis by generating a mutated cell or animal, when it would have taken two or three years before. To achieve results and remain competitive, it is crucial to support research financially. If ever there were a time when the effects of science were measurable, it’s now!

PSL: As a woman researcher who has achieved international renown, do you have anything you’d like to say to young women just starting a career in research?

Go for it! Don’t consider any doors closed, and train your future students and employees (both men and women) to see equality in the sciences as the natural state!

EH: My message is simple: if you’re excited about research, then go for it, and don’t waste time worrying about what is or is not possible. You can have a family and live your life however you wish while being a scientists. There are no contraindications, if you will. (laughs) More seriously, I come from a generation that had no doubt that there was a place for women, or at least that there should be one. In any case, I don’t remember ever feeling like there was a glass ceiling at the beginning of my career. I see things differently now: being a young woman in research is not always easy, especially at times when the economy is weak. So it’s important to stay on our toes and promote women at every level, when we can. I have been saddened to find myself at meetings surrounded largely by men, but I am very hopeful. We have trained a generation with enough female skill and talent to claim a certain parity. So--go for it! Don’t consider any doors closed, and train your future students and employees (both men and women) to see equality in the sciences as the natural state!

PSL: 2017 was a year of many accomplishments: you were appointed head of the EMBL (European Molecular Biology Laboratory) and honored with the Grand Prix Inserm. What are your plans for 2018?

This year will be a little quieter, I hope! I take my role as a professor at Collège de France very seriously. Being a good teacher is difficult, but it is also an unparalleled opportunity to be in contact with the public and draw attention to the power and beauty of basic research. If I can inspire just one person who then goes on to do something that helps the planet or advances science, then the effort has been worthwhile! Taking charge of the EMBL is also a very exciting challenge. I am very attached to the EMBL’s projects: their European scope, commitment to basic and applied research, effort to advance knowledge and transfer the results of cutting-edge research to the people... I would not have accepted any other role, and I hope I can contribute to the European project in these difficult times.