GRK 2581:  Metabolism, topology and cx)mpartmentalization of membrane proximal lipid and signaling components in infection

• Subject Area: Microbiology, Virology and Immunology
• Term: from 2020 to 2024
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 417857878

In spite of the availability of preventive strategies, infectious diseases continue to be a major threat worldwide. Therefore, there is a demand for continuous development of anti-infective or immuno-therapeutic strategies, in particular for conditions where conventional interventive means are not available, prohibited or fail. To control infectious diseases, novel interventive strategies should therefore effectively modulate 1) innate and adaptive immune responses and/or 2) tissue and cell compartment specific autonomous metabolic parameters all - of which operate to limit (or in some instances also promote) both pathogen spread and tissue damage. Common denominators of these cellular processes are dynamic alterations in membrane metabolism. This efficiently defines compartmentalization of the repertoire of host and immune cell receptors, associated signaling pathways, cytoskeletal dynamics and effector mechanisms. Because sphingolipids are major components of membranes, sphingolipid biosynthesis and metabolism and availability of their signaling inert or bioactive species substantially affects the biophysical properties of membranes and the subcellular redistribution of receptors and signaling complexes. This may essentially regulate pathogen uptake and handling at a cellular and organismic level as well as survival and activity of immune cells where they shape the magnitude and quality of the individual cellular compartments acting to control a given pathogen. Targeted intervention of sphingolipid turnover has proven to be a successful strategy in inflammation, but its potential as a target in controlling infectious diseases at the level of metabolism and immune controls requires further definition. Therefore, the RTG initiative aims to identify and validate targets for novel anti-infective or immunotherapeutic strategies targeting infectious diseases at the level of modulation of the sphingolipid metabolism. As a long-term perspective, rationally defined synthetic sphingolipid analogues or metabolizing enzymes will be evaluated for therapeutic options in the respective different models of infectious diseases models. These ambitious goals demand multidisciplinary training of a new generation of young scientists trained within the RTG which virill be capable of integrating and implementing cutting edge basic and clinical infectiology (EA, LD, MF, VKP, OK. TR, SSS, ASU, FA, MR, AW), immunology (NB. WK). high-end microscopy (MS, CS), bio- and organic chemistry (MS. JS, BK) as well as lipid and protein analytics (JS, BK, FS) and their bioinformatic processing (FE).

• DFG Programme: Research Training Groups
• Applicant Institution: Julius-Maximilians-Universität Würzburg
• Spokesperson: Professor Dr. Jürgen Seibel
• Participating Researchers: Dr. Elita Avota; Privatdozent Dr. Niklas Beyersdorf; Professor Dr. Lars Dölken; Privatdozent Dr. Martin J. Fraunholz; Professor Dr. Wolfgang Kastenmüller; Professor Dr. Burkhard Kleuser; Professorin Dr. Vera Kozjak-Pavlovic; Professor Dr. Oliver Kurzai; Professor Dr. Thomas Rudel; Professor Dr. Markus Sauer; Professorin Dr. Sibylle Schneider-Schaulies; Professorin Dr. Alexandra Schubert-Unkmeir; Professor Dr. Christian Stigloher; Professor Dr. John Ziebuhr