Transregio SFB-TR 84 “Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia“

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Area C

Control of host response in the bronchoalveolar compartment and strategies of intervention

 

Area C is dedicated to important mechanisms of controlling and limiting pulmonary inflammation, and the testing of innovative intervention procedures.

Project C1 (Schmeck, Marsico) will perform deep phenotyping and computational analysis of the infected host cell responses in comparison of infected and uninfected bystander cells and test the effect of junctional knock-out of lead targets in Legionella infection. By using complex, clinically relevant mouse and pig infection models, as well as functional pathway analysis, project C6 (Witzenrath, Weissmann) will analyse the therapeutic usability of vasculotide as a new adjunctive strategy in pneumonia. Combining their complimentary expertise in carbohydrate chemistry/vaccinology and infection immunology, the teams in project C8 (Seeberger, Sander) will develop a new generation of fully synthetic, highly efficacious vaccines by taking in particular advantage of MAIT cell activity. The PIs Kübler, Suttorp and Witzenrath in project C9 focus on their observation that Pneumococci impair CFTR function and presence. Consequently, they will provide an in-depth investigation of underlying pathways (WNK1, VGCC, TRPV4) and consequences for lung function in pneumonia. A comprehensive analysis of the RNA-editome, the function of individual lincRNAs and innovative thereon based intervention studies characterize the project C10 of Sander, Schulte and Bauer.

Abbreviations: B/Gi-M, Berlin/Gießen-Marburg; B, Berlin; mRNA, messenger RNA; miRNA, microRNA;  lncRNA, long non-coding RNA; circRNA, circular RNA; L.p., Legionella pneumophila; bacs, bacteria; Tie-2,  tyrosine-protein kinase receptor-2; VT, vasculotide (synthetic Tie-2 ligand); Vita-PAMP, viability-associated PAMP; carbohyr, carbohydrates; SP3tetra, synthetic tetrasaccharide from S.p. capsule; 5-OP-RU, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil; APC, antigen presenting cell; ST3-sp-B cell, S. pneumoniae serotype 3 tetrasaccharide-specific B cells; S.p., S. pneumoniae; CFTR, cystic fibrosis transmembrane conductance regulator; AA, arachidonic acid; Cl-, chloride; WNK1, lysine deficient protein kinase 1; ADAR, double-stranded RNA-specific adenosine deaminase; APOBEC, apolipoprotein B mRNA editing catalytic polypeptide-like kinase; E.c., Escherichia coli;  K.pn.; Klebsiella pneumoniae.
The human figure indicate projects with primary human lung tissue and use of clinical human samples, and the pig figure indicate pig infection models.