SFB 617:  Molecular mechanisms of epithelial defense

• Subject Area: Biology
• Term: from 2002 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5485085

It is the aim of the collaborative research centre to investigate, why healthy body surfaces - despite the continous presence of potentially pathogenic microorganisms - usually are not infected and how epithelia actively defend infection-independent from specialized leukocytes of the immune system. One focus will be on microbicidal peptides and proteins of different epithelial origin. In particular, we will analyse such peptides obtained from the invertebrate Hydra, from human origin (from human skin, the gastrointestinal tract and the lung), from cow skin as well as from mouse skin. Both, constitutively produced antimicrobial peptides, which act against a more or less restricted spectrum of microorganisms, and other, by contact of epithelial cells with pathogens induced antimicrobial peptides, will be analysed. Furthermore, by pathogens produced inducers of antimicrobial peptides in epithelial cells and factors that cleave inactive precursors of epithelial peptide antibiotics to generate active forms as well as microbial factors that induce production of proinflammatory cytokines in epithelial cells, will be structurally characterised. We will analyse, which peptide antibiotics are induced by these "pathogen-associated molecules" in different epithelia. Furthermore, by recombinant techniques generated antimicrobial peptides will be investigated for their biophysical and physico-biochemical properties to get an idea about the mode of action of these peptides in microbial killing. We hope to get progress in understanding the strategy, how healthy epithelia keep healthy. Our findings should give new ideas in understanding the pathophysiology of locally occuring recurrent infections, in particular in the skin, the gut, the genito-urinary tract and the lung. A major aim of our project will be also to present basic knowledge to generate a new generation of antibiotics, which, due to its completely different mode of action, could represent future alternatives to fight against pathogens that are resistant towards classical antibiotics. Search for inducible peptide antibiotics and the discovery of pathogen-associated molecules that induce petide antibiotics, but not proinflammatory cytokines, should allow new concepts of "immune stimulation" of the epithelial innate immune system.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Molekulare Mechanismen der epithelialen Abwehr im stammesgeschichtlich alten Vielzeller Hydra (Project Head Bosch, Thomas C. G. )
• A02 - Untersuchungen zur Rolle neuer antimikrobieller Peptide der menschlichen Haut (Project Head Schröder, Jens-Michael )
• A03 - Bedeutung von humanen epithelialen RNasen für die Infektionsabwehr (Project Head Harder, Jürgen )
• A04 - Bakterielle Pathogen-assoziierte Moleküle als Induktoren der Synthese epithelialer antimikrobieller Peptide des Menschen (Project Head Schröder, Jens-Michael )
• A06 - Mikrobielle Proteasen als Induktoren der antimikrobiellen Abwehr der Haut (Project Head Wiedow, Oliver )
• A07 - In vivo Regulation von physikalischer und chemischer Hauptbarriere in der epithelialen Abwehr von Mikroorganismen (Project Head Proksch, Ehrhardt )
• A08 - Funktion von Matrixmetalloproteinasen in epidermalen Aufbau- und Abwehrmechanismen und bei der Regulation der Aktivität von antimikrobiellen Peptiden (Project Head Sedlacek, Radislav )
• A09 - Strukturaufklärung antimikrobieller Peptide und Proteine mit Hilfe der NMR-Spektroskopie (Project Head Grötzinger, Joachim )
• A12 - Die Aktivierung humaner Bronchialepithelzellen durch bakterielle Zellwandbestandteile und CpG-Oligonukleotide: Rezeptoren, Signalübertragung und Freisetzung von Mediatoren (Project Heads Heine, Holger ;  Ulmer, Artur Jochen )
• A13 - Bedeutung von antimikrobiellen Peptiden im menschlichen Gastrointestinaltrakt (Project Heads Arlt, Alexander ;  Kiehne, Karlheinz )
• A15 - Untersuchungen zur Bedeutung epithelialer antimikrobieller Peptide im bovinen Milchdrüsengewebe (Project Heads Kalm, Ernst ;  Looft, Christian )
• A16 - Rolle von Gamma-T-Lymphozyten in der epithelialen Abwehr (Project Head Kabelitz, Dietrich )
• A17 - Biophysikalische Untersuchungen zur Lipidspezifität membranaktiver antimikrobieller Peptide/Proteine der epithelialen Abwehr (Project Head Seydel, Ulrich )
• A18 - Molekulare Basis der epithelialen Abwehr in den wirbellosen Modellorganismen (Project Head Leippe, Matthias )
• A19 - Aufklärung der NOD-ähnlichen-Resistenzprotein (Hs1-1pro1) initiierten Signaltransduktion in Arabidopsis thaliana (Project Head Cai, Daguang )
• A20 - Funktionelle Charakterisierung der NOD Proteine NOD3 und 27: Bedeutung für die immunologische Barrierefunktion des Darmes und die Pathophysiologie chronisch-entzündlicher Darmerkrankungen (Project Head Rosenstiel, Ph.D., Philip Caspar )
• A21 - Regulation der Expression epidermaler antimikrobieller Peptide durch ultraviolette Strahlung (Project Head Schwarz, Thomas )
• A22 - In vitro- und in vivo-Untersuchungen zur Bedeutung antimikrobieller Peptide im Bewegungsapparat (Project Heads Mentlein, Rolf ;  Varoga, Deike )
• A23 - Die Rolle antimikrobieller Peptide bei der COPD (Project Heads Heine, Holger ;  Lange, Christoph )
• A24 - Epitheliotrope Funktionen des T-zellulären Zytokins IL-26 und seines Rezeptors (Project Head Fickenscher, Helmut )
• Z01 - Empfindlichkeitsteste zur Identifikation humaner antimikrobieller Peptide (Project Head Podschun, Rainer )
• Z02 - Rekombinante Synthese humaner antimikrobieller Peptide und Proteine (Project Heads Grötzinger, Joachim ;  Harder, Jürgen )
• Z03 - Zentrale Aufgaben des Sonderforschungsbereichs (Project Head Schröder, Jens-Michael )

• Applicant Institution: Christian-Albrechts-Universität zu Kiel
• Participating Institution: Forschungszentrum Borstel; Leibniz Lungenzentrum
• Spokesperson: Professor Dr. Jens-Michael Schröder