Projektbeschreibung
Lipopolysaccharide in Darmbakterien: noch ein immunologisches Rätsel
Lipopolysaccharide (LPS) sind Glykolipide auf der äußeren Membran gramnegativer Bakterien, die Entzündungsreaktionen auslösen können. LPS finden sich auch auf der Membran harmloser, nützlicher Darmmikroben, sind dort merkwürdigerweise aber immunologisch „stummgeschaltet“. Das EU-finanzierte Projekt DEBUGGING-LPS untersucht, wie es zu dieser LPS-Immunogenität kommt. Der Arbeitshypothese zufolge bewirkt die einzigartige chemische Zusammensetzung der LPS dieser Darmbakterien, dass im Darm ein Signal für Immuntoleranz erzeugt wird. Ziel des Projekts ist Grundlagenwissen zu lokaler und systemischer Immunität sowie zur symbiotischen Beziehung zwischen Kommensalen/Darmmikroben und Wirt. Das neue Wissen könnte den Weg für neue Therapien gegen Immunerkrankungen eröffnen.
Ziel
Gut Microbiota is a key actor for human health, driving many physiological and pathological processes, including immune system development and modulation. How this massive population of microorganisms, most of which are bacteria, establishes commensal, mutualistic or pathogenic interactions with the human host despite the vigilance of the immune system, is still obscure and requires an in-depth study. The story gets more intricate considering that gut is home for a myriad of Gram-negative bacteria whose outer membrane main constituent is the lipopolysaccharide (LPS). Due to its chemical structure, LPS is considered a potent elicitor of immune inflammatory reactions in mammals, being usually associated to perilous bacteria and detrimental outcomes for human health. Nevertheless, LPS also decorates the membrane of harmless and beneficial Gram-negatives of gut microbiota. How LPS is tolerated and remains (apparently) silent in the gut is a major unsolved question representing a frontier in our understanding of innate immunity.
DEBUGGING-LPS project will contribute to answer this question, starting from the assumption that the chemistry of LPS is the real message taken from human host of the bacterial interaction, either beneficial or harmful. Strategically based on my expertise in organic chemistry, and integrating synthetic chemistry and cellular immunology studies, DEBUGGING-LPS will decrypt the 'chemical language' spoken by LPS in the gut. This project will deliver a clear picture of the chemistry at the basis of the difference between 'good' and 'bad' LPS, providing tools for the exploitation of the acquired knowledge to create novel therapeutics for resolving/mitigating immune disorders. DEBUGGING-LPS has been conceived to go beyond the state-of-the-art, breaking the dogma of LPS as an enemy, leaving space for a new vision of this glycomolecule: i.e. no longer as a toxic bacterial product rather as an immune signal vital for the proper functioning of our body.
Wissenschaftliches Gebiet
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
HORIZON-AG - HORIZON Action Grant Budget-BasedGastgebende Einrichtung
80138 Napoli
Italien