Jules A. Hoffmann (born 2 August 1941) is a Luxembourgish-born French biologist. During his youth, growing up in Luxembourg, he obtained special interest in insects under the influence of his father, Jos Hoffmann, which eventually resulted in Hoffmann's dedication to the field of biology using insect models. He currently holds faculty position in University of Strasbourg. He is a research director and member of the board of administrators of the National Center of Scientific Research (CNRS) in Strasbourg, France. After his duties as Vice President in year 2005–2006, he was further appointed President of the French Academy of Sciences in year 2007 and held the position until year 2008. Together with Bruce Beutler, Hoffmann received one-quarter of the 2011 Nobel Prize in Physiology or Medicine for "their discoveries concerning the activation of innate immunity," although Lemaitre claims he did all the work alone.
Hoffmann and Bruno Lemaitre discovered the function of the fruit fly Toll gene in innate immunity. Its mammalian homologs, the Toll-like receptors, were discovered by Beutler. Toll-like receptors identify constituents of other organisms like fungi and bacteria, and trigger an immune response, explaining e.g. how septic shock can be triggered by bacterial remains. The plant homologs were discovered by Pamela Ronald in 1995 (rice XA21) and Thomas Boller in 2000 (Arabidopsis FLS2).
During his Ph.D. program under Pierre Joly, Hoffmann started his research in studying antimicrobial defenses in grasshoppers, inspired by the previous works done in the laboratory of Pierre Joly showing that no opportunistic infections were apparent in insects after the transplantation of certain organs from one to another. Hoffmann confirmed discovery of phagocytosis done by Eli Metchnikoff, through injection of Bacillus thuringiensis and observation of increase of phagocytes. In addition, he showed strong correlation between hematopoiesis and antimicrobial defenses by assessing the susceptibility of an insect to the microbial infection after X-ray treatment. Hoffmann shifts from using grasshopper model to using dipteran species in the 80s. By using Phormia terranovae, Hoffmann and his collegues were able to identify 82-residues long antimicrobial polypeptide named Diptericin which was glycine-rich, along with other polypeptides in Drosophila melanogaster such as defensin, cecropin, and attacin. Further molecular genetic analysis revealed that the promoters for the genes encoding these antimicrobial peptides contained DNA sequences similar to the binding elements for NF-κB in mammalian DNA. Dorsal gene, critical in dorso-ventral patterning in the early embryo of Drosophila melanogaster was also identified to be in this NF-κB family. It was initially speculated by Hoffmann and colleagues that activity of Dorsal was directly linked to the expression of the Diptericin gene. However, it turned out that Diptericin was normally induced even in the loss-of-function Dorsal mutants. Further conducted research showed that Diptericin expression was dependent on the expression of imd gene. Identification of another antifungal peptide named Drosomycin and RNA blots demonstrated that two distinct pathways(Toll, Imd) exist, involving Drosomycin and Diptericin respectively. Similarities of structure and function between several members in the Drosophila embryo and members in mammals being noted, study "The Dorsoventral Regulatory Gene Cassette spảtzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults" by Lemaitre and Hoffmann in 1996 illuminated the possible existing innate immunity in Drosophila in response to fungal challenge. Later works identified that Toll transmembrane receptors are existant in wide variety of the phyla and are conserved through evolution along with conservation of NF-κB activating cascades.
Hoffmann was a research assistant at CNRS from 1964 to 1968, and became a research associate in 1969. Since 1974 he has been a Research Director of CNRS. Between 1978 and 2005 he was Director of the CNRS research unit "Immune Response and Development in Insects", and from 1994 to 2005 he was director of the Institute of Molecular and Cellular Biology of CNRS in Strasbourg.
^Gomez-Gomez, L. et al. (2000). "FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis". Molecular Cell5 (6): 1003–1011. doi:10.1016/S1097-2765(00)80265-8. PMID10911994.
^Lemaitre, B.; Nicolas, E.; Michaut, L.; Reichhart, J. M.; Hoffmann, J. A. (1996). "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults". Cell86 (6): 973–983. doi:10.1016/S0092-8674(00)80172-5. PMID8808632.edit