Co-founder and former CIML Director
Professor Michel Fougereau has contributed to the emergence of an authentic "French school of immunology." He founded the first Immunology teaching module at the Faculty of Science and one of the leading Health and Life Sciences graduate schools. He ended his career as a consultant in this sector for the Ministry of Higher Education and Research.
From New York to Paris, study of the structure and diversity of antibodies
A graduate of the Toulouse Veterinary School, he was appointed assistant to the Central veterinary research laboratory at Alfort, in Alain Paraf's department. At the same time he attended classes at the Faculty of Science in Paris, which was dominated by two prominent figures in the history of biology: the geneticist Piotr Slononimski and future Nobel Prize winner Jacques Monod. This latter opened him the way to the prestigious Rockefeller Institute in New York where he prepared a doctoral thesis supervised by Gerald M Edelman. "At the time, Gerald Edelman was trying to solve one of the most captivating puzzles in biology: how do we manage to produce millions of different antibodies from such a limited number of genes?" recalls Michel Fougereau. "The first steps involved the shedding of light on the structure of immunoglobulin chains." Eight years later, Gerald M Edelman and Rodney Porter were awarded the Nobel Prize in Medicine for their discoveries concerning the chemical structure of antibodies.
He returned to France in 1965 to the new INRA, Virology & Immunology Station founded by Alain Paraf at Thiverval-Grignon, for some time he continued studying the immunoglobulin structure, this time in the pig and sheep.
From the discovery of the "French sequence" to the creation of the first "comprehensive" immunology centre: the CIML
In 1969, he was appointed Professor at Aix-Marseille University. With his team from the Biochemistry and Molecular Biology Centre (CNRS, Marseille), he then began to work on the structure of antibodies, leading a few years later, to the finding of the first complete sequence of mouse immunoglobulin known in the United States as the "French sequence". This long-term work enabled him to tackle various issues relating to genetic antibodies, in collaboration with several groups from the Pasteur Institute, including Jacques Oudin who discovered the concept of immunoglobulin allotypes and idiotypes.
In 1973, the creation of a CNRS immunology research institute in Marseille-Luminy was suggested to Michel Fougereau by Claude Levy, director of the CNRS at the time, this idea was shared by François Kourilsky who also intended to establish an INSERM Unit in this discipline. In 1976 the CIML was founded from a merger of these two approaches, made possible by agreement of the two trustees. "The goal was to bring together research teams from different cities in France on a single site and to open this site to immunologists from around the world," recalls Michel Fougereau. An openness culture fiercely preserved by CIML members today, as it still houses 24 nationalities. Among these pioneers, at that time were Michel Delaage; also from the CBBM, Marseille and future founder of the company Immunotech, Claude Mawas HLA system specialist and Pierre Golstein who then sought to understand how T cells kill infected or cancerous cells. The works of the latter led to the discovery of the CTLA-4 receptor, which gave birth 15 years later, to the monoclonal antibodies used with the success that we now know today in anti-cancer immunotherapy.
From the introduction of molecular biology methodologies to the study of B-cell differentiation
After solving the repertoire riddle, researchers are now tackling the multiple cellular and molecular players involved in the immune response. "In the late 70s, attention was mainly focused on the adaptive immunity players," stresses Michel Fougereau. "This is the period of major works on the genetic diversity of immunoglobulin and T cells and also on the limitations of self and non-self discrimination." In this perspective, from its opening CIML adopted a wide range of necessary biochemical tools (the sequencing of amino acids, peptide separator...) and launched its first molecular biology platform used by Bertrand Jordan to carry out the successful sequencing of the first HLA Gene.
Back from a sabbatical at the Pasteur Institute in Paris, Michel Fougereau then concentrated on the early stages of B-cell development and his team developed tools to explore the early stages of their differentiation in bone marrow, this time moving from the mouse system to the human model. The identification of a mouse transcript homologous to the lambda 5 gene constitutes the first step in an approach that will be successfully continued by Claudine Schiff up to the structural and functional characterisation of the human Pre-B cell receptor, and the identification of its ligand.
From teaching a "new discipline" to the academic and industrial spin-offs
The contribution of Michel Fougereau has not just been limited to his laboratory: from the beginning he wished to be a "driving force for science". Accordingly, he created the first immunology teaching module at the Science Faculty. For the discipline this stage was a turning point both in form (until the early 70s, university education in this branch was exclusively provided by medical faculties) and in substance: training is structured around four themes – cellular and molecular immunology, immunogenetics and immunopathology - widely taught by CIML researchers. In the process, he published a book, "Eléments d’immunologie fondamentale" to accompany several generations of students, developed second and third cycle studies in immunology and then in 1992 launched one of the top graduate schools in Health & Life sciences in Marseille. Forty years after the foundation of the Immunology Centre, the graduate school is one of the largest in France (600 students and 120 thesis per year on average) and the CIML is also considered one of the best schools in immunology research in the world. Transmission to the general public is also provided through its “Que Sais-Je?-Immunologie" and other articles of general interest.
One of its first students, Bernard Malissen, would become one of the finest talents in the CIML, which he directed for ten years and "renovated" with the informed support of its administrator Daniel Francal, before founding the Centre for Immunophenomics Centre CIPHE in Luminy. This is one of the latest spin-offs, preceded long ago by many others. From 1981, i.e. 3 years before the Nobel Prize was awarded jointly to G. Köhler and C. Milstein, after a sabbatical leave in Oxford, François Kourilsky launched the monoclonal antibody technology at the CIML. Several months later, he participated in the establishment of Immunotech, which, under the brilliant steering of Michel Delaage and Antoine Beret will experience the success that we know today. At the same time, monoclonal antibody technology shall be widely exploited by several CIML teams, in particular by Michel Pierres a true master of the art.
Since then, the CIML continues to contribute to spread, directly or indirectly, all stages of the innovation chain: fundamental research (CRCM), translational research (MI-mAbs, CIPHE and the TAGC laboratory) and industry (Innate Pharma, Ipsogen, OzBiosciences...), and more recently, through the cluster Marseille Immunopole, launched at the initiative of its current director Eric Vivier, the leading specialist in innate immunity.
Consequently, the heirs of the INSERM-CNRS structure created 40 years ago, and recently extended to Aix-Marseille University, can they and should they feel vested with the pioneering spirit, which is still today the "trademark" of its two co-founders.
Michel Fougereau, Doctor of Veterinary Medicine and Doctor of Science, is professor emeritus at Aix-Marseille University (AMU). He began his career at the Central veterinary research laboratory at Alfort, joined the Rockefeller University in New York where he prepared his science thesis, he then joined the INRA at Thiverval-Grignon before being appointed professor at Marseilles and team leader at the CNRS Molecular Biology Center. CIML co-founder, he migrated there with his team at its opening. He ended his career as Health and Life Sciences consultant to the Ministry of Research.
The scientific work of his team initially focused on the structure and genetic origin of the diversity of immunoglobulin, before turning to the study of the early stages of human B cell differentiation, in conjunction with certain primary immunodeficiencies.
Contribution to immunology teaching
Michel Fougereau has played a key role in the organisation of training in this discipline. In Luminy he developed second and third cycle studies in immunology, founded and directed the graduate school in Health & Life Sciences in Marseille in 1992 and has on several occasions held international courses under the auspices of NATO. Finally, he created the annual training course at the French Society for Immunology.