Jules A. Hoffmann

CNRS) in Strasbourg, France. He was elected to the positions of Vice-President (2005–2006) and President (2007–2008) of the French Academy of Sciences.^[3] Hoffmann and Bruce Beutler were jointly awarded a half share of the 2011 Nobel Prize in Physiology or Medicine for "their discoveries concerning the activation of innate immunity,".^[4]

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, for example, how septic shock can be triggered by bacterial remains.^[5][6][7]

Marburg an der Lahn, Germany

Eli Metchnikoff, through injection of Bacillus thuringiensis and observation of increase of phagocytes.^[2] 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.^[2] Hoffmann shifts from using grasshopper model to using dipteran species in the 80s. By using Phormia terranovae, Hoffmann and his colleagues 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.^[2] 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 spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults"^[8] 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 present in a wide variety of phyla and are conserved through evolution along with conservation of NF-κB activating cascades.^[2]

United States National Academy of Sciences^[when?], the American Academy of Arts and Sciences, the Fondation Écologie d'Avenir^[9] and the Russian Academy of Sciences