Emmanuelle CHARPENTIER
Winner of the 2015 Louis-Jeantet Prize for medicine

Born 1968 in Juvisy-sur-Orge (France), Emmanuelle Charpentier studied biochemistry and microbiology at the Pierre & Marie Curie University of Paris, and obtained her PhD at the Institut Pasteur. She then continued her work in the United States at the Rockefeller University, the New York University Medical Center, and then the St Jude Children’s Research Hospital in Memphis. After returning to Europe, she set up a research group in microbiology at the Max F. Perutz Laboratories of the University of Vienna (Austria). Subsequently she was appointed Associate professor and then Guest Professor at Umeå University (Sweden). Since 2013, she is Head of the Department of Regulation in Infection Biology at the Helmholtz Centre for Infection Research in Braunschweig, Germany, and Professor at the Medical School of Hannover.

Emmanuelle Charpentier was elected member of the European Molecular Biology Organization (EMBO) in 2014, and was selected as one of the American Foreign Policy magazine’s 100 Leading Global Thinkers for 2014. She has already received numerous awards for her research, including in 2014 the Alexander von Humboldt Professorship, the Dr Paul Janssen Award, the Grand-Prix Jean-Pierre Lecocq (French Academy of Sciences), the Göran Gustafsson Prize (Royal Swedish Academy of Sciences) and in 2015 the Breakthrough Prize in Life Sciences.

“Scissors” for cleaving genes

Pathogenic bacteria possess an immune system that defends them against predators, and particularly against attacks by viruses (bacteriophages). When examining how this defence system works for Streptococcus pyogenes, Emmanuelle Charpentier’s team noted that it uses a duplex of two small RNA molecules that contain sections of the virus genome (or CRISPR) and thus carry the memory of a previous attack. The microbiologists furthermore discovered that the CRISPR acted as the guide for a protein (Cas9), which kills the virus by cleaving its genome at particular points. So these two entities grouped together, the CRISPR-Cas9 complex, permit the streptococcus to resist virus attacks.

Emmanuelle Charpentier and co-workers then profited from this existing defence mechanism of bacteria, using it to make CRISPR-Cas9 into a real tool for cleaving the DNA of bacterial and also human cells at precise points. These “genetic scissors” can be used for targeting any gene in a cell in order to modify it. It is henceforth possible to modify gene expression, to switch it “on” or “off”, to change, repair or remove genes. This new tool is now used in molecular biology laboratories around the world. It could also revolutionize medicine by paving the way to finding new forms of treatment for currently incurable diseases.

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).

Professor Emmanuelle Charpentier

Contact in Germany:
Helmholtz Centre for Infection Research
Head
Department Regulation in Infection Biology
Inhoffenstrasse 7
38124 Braunschweig
Germany

Telephone: +49 531 6181-5500


http://www.helmholtz-hzi.de

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

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