Emmanuelle CHARPENTIER
Lauréat du Prix Louis-Jeantet de Médecine 2015

Née en 1968 à Juvisy-sur-Orge (France), Emmanuelle Charpentier a étudié la biochimie et la microbiologie à l’Université Pierre et Marie Curie de Paris, puis a obtenu son doctorat à l’Institut Pasteur. Elle est ensuite partie aux Etats-Unis où elle a poursuivi ses travaux à la Rockefeller University et à la New York University Medical Center, puis au St Jude Children’s Research Hospital à Memphis. De retour en Europe, elle a créé un groupe de recherche en microbiologie au Max F. Perutz Laboratories de l’Université de Vienne (Autriche), puis a ensuite été nommée professeur associée et professeur invitée à l’Université d’Uméa (Suède). Depuis 2013, elle dirige le département Regulation in Infection Biology au Centre Helmholtz de recherche sur les maladies infectieuses à Braunschweig et est professeure à l’école de médecine d’Hanovre en Allemagne.

Élue membre de l’Organisation européenne de biologie moléculaire (EMBO) en 2014, Emmanuelle Charpentier a figuré dans la liste des 100 principaux penseurs mondiaux établie en 2014 par le magazine américain Foreign Policy. Elle a déjà reçu de nombreuses distinctions, notamment, en 2014, l’Alexander von Humboldt Professorship, le prix Dr Paul Janssen, le Grand-Prix Jean-Pierre Lecocq de l’Académie des sciences françaises et le prix Göran Gustafsson de l’Académie royale suédoise, ainsi que Breakthrough Prize in Life Sciences 2015.

Des «ciseaux» pour couper les gènes

Les bactéries pathogènes possèdent un système immunitaire qui leur permet de lutter contre leurs prédateurs, en particulier contre les virus (les bactériophages) qui les attaquent. En étudiant le mode de fonctionnement de ce système de défense chez le Streptococcus pyogenes, l’équipe d’Emmanuelle Charpentier a constaté qu’il utilisait un duplex de deux petites molécules d’ARN renfermant des fragments du génome du virus (nommé CRISPR), qui portent ainsi la mémoire d’une précédente agression. Les microbiologistes ont d’autre part découvert que le CRISPR servait de guide à une protéine (Cas9), qui tue le virus en coupant son génome en des points particuliers. C’est donc l’assemblage de ces deux entités, le complexe CRISPR-Cas9, qui permet au streptocoque de résister aux virus.

Emmanuelle Charpentier et collègues ont alors entrepris de détourner cet ancien mécanisme de défense des bactéries, afin de faire du CRISPR-Cas9 un véritable outil capable de sectionner un ADN – d’une cellule bactérienne, mais aussi humaine – en des endroits précis. Ces «ciseaux génétiques» permettent de cibler n’importe quel gène dans une cellule, afin de le modifier. Il devient ainsi possible de changer son expression – de «l’allumer» ou de «l’éteindre» – de modifier, de réparer ou d’ôter des gènes. Ce nouvel outil est aujourd’hui utilisé dans les laboratoires de biologie moléculaire du monde entier. Il pourrait aussi révolutionner la médecine en ouvrant la voie à des traitements de maladies encore incurables.

CRISPR-Cas9 has recently emerged as a powerful and universal technology for gene editing with wide-ranging implications across biology and medicine. The technology functions as molecular scissors to perform precise surgery on genes and various versions of the system have been developed to broaden its range of applications to manipulate genes and their expression in a large variety of cells and organisms. CRISPR-Cas9 has quickly been adopted by the community of biologists around the world and is now recognized as a transformative technology in various fields of research with great potential to benefit the understanding and treatment of human genetic diseases, cancers or infectious diseases.
Originally, the system is an ancient mechanism of immunity that allows bacteria to defend themselves against their predators, e.g. the viruses of bacteria also called phages. Bacteria have existed as the first forms of life to appear on earth and are essential to our existences. Yet, we are far from understanding their diversity and the multiple mechanisms they have evolved to interact with their environment that includes their predators and the human host. This is the focus of Emmanuelle Charpentier’s research: decipher fundamental molecular mechanisms involved in bacteria. During the last decades, humans have largely exploited bacteria. Bacteria have revolutionized molecular biology as an unlimited source of enzymes and they are extensively used in industry in various ways (for example, as probiotics, for the manufacture of diary products, production of biological substances such as enzymes, vaccines, antibiotics and biofuels). Most bacteria are harmless or even beneficial but several are pathogenic. This is the case of Streptococcus pyogenes, the source of the CRISPR-Cas9 technology. S. pyogenes also known as Group A streptococcus is a gram-positive bacterial pathogen responsible for a wide range of human diseases including necrotizing fasciitis, commonly known as the flesh eating disease.
Emmanuelle Charpentier’s research is mostly driven by a strong motivation to understand fundamental mechanisms of regulation in bacterial pathogens with the aim to generate new findings that could possibly be translated into innovative biotechnology and biomedical applications. By studying regulatory mechanisms involved in pathogenic bacteria, novel biological targets and pathways can be identified and potentially harnessed for the development of novel anti-infectives. New strategies to manipulate genomes and cells with a broader range of applications can also be unravelled, as exemplified recently by the work of Emmanuelle Charpentier and co-workers on the S. pyogenes CRISPR-Cas9 system (Fig. 1).

Figure 1: The CRISPR-Cas9 system and its applications.
The Cas9 enzyme (blue) generates breaks in double-stranded DNA by using its two catalytic centers to cleave each strand of a DNA target site (light green) next to a PAM sequence (orange) and matching the 20-nucleotide sequence (light green) of the single guide RNA (sgRNA). The sgRNA includes a dual-RNA sequence derived from CRISPR RNA (black) duplexed to a separate transcript (tracrRNA, red) that binds to the Cas9 protein. Cas9-sgRNA–mediated DNA cleavage produces a blunt double-stranded break that triggers repair enzymes to remove or replace DNA sequences at or near the cleavage site. The potential of the system was demonstrated in a large variety of cells and organisms.

Emmanuelle Charpentier’s laboratory is particularly interested in understanding how regulatory RNAs and proteins coordinate the modulation of gene expression at the transcriptional, post-transcriptional and post-translational level in processes of infection and immunity. What are the mechanisms involved in the adaptation of bacteria to various stress conditions, their survival and persistence within the host or their evasion of host immunity? Emmanuelle Charpentier’s team particularly researches on (i) interference systems involved in the defense against mobile genetic intruders (CRISPR-Cas), (ii) small regulatory RNAs that interfere with pathogenic processes, (iii) toxin-antitoxin systems, (iv) protein quality control that regulate bacterial adaptation, physiology and virulence, and (v) the mechanisms of bacterial recognition by immune cells (Fig. 2).

Figure 2: Molecular regulatory pathways involved in the interactions of bacteria with the human host (e.g. epithelial, endothelial and immune cells) and the mobile genomes (e.g. phages, plasmids).

Professeure Emmanuelle Charpentier

En Allemagne:
Helmholtz Centre for Infection Research
Head
Department Regulation in Infection Biology
Inhoffenstrasse 7
38124 Braunschweig
Allemagne

Téléphone: +49 531 6181-5500


http://www.helmholtz-hzi.de

En Suède:
Molecular Infection Medicine Sweden MIMS
Umeå Centre for Microbial Research UCMR
Department of Molecular Biology, Room 6K-137
Umeå University
SE-901 87hhj Umeå
Suède

Téléphone: +46 90 7850815 (office), +46 90 7850810 (lab)