FOR 2123:  Sphingolipid Dynamics in Infection Control

• Subject Area: Medicine
• Term: from 2014 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 242127429

Having long been considered abundant, yet inert components of the cell membrane, sphingomyelin and its metabolites, especially ceramides, are meanwhile recognised as important regulators of membrane microdomain activity because they are essential in compartmentalising membrane proteins and membrane proximal signalling components. In contrast to their intensely studied role in cancer biology, the role of sphingolipids and their breakdown products in steps decisive for the interaction of a host cell with pathogens such as attachment, entry or invasion, intracellular trafficking, compartmentalisation and regulation of cell autonomous defence is poorly addressed. Because immune responses can also be regulated at the level of sphingolipid dynamics, this pathway most likely controls decisive elements in the pathogenesis of infectious diseases where pathogen uptake, spread and dissemination are counteracted by host cell autonomous, innate and adaptive immune responses.
Core topical elements of the Research Unit are, therefore, to decipher the regulatory role of sphingolipid dynamics both at the host and pathogen level in addressing (1) adhesion, activation, differentiation and effector functions of T cells at a molecular and cellular level as well as experimental infection models and (2) pathogen adhesion and invasion, trafficking and modulation of host cell functions essential in the control of bacterial pathogens. To accomplish these goals, the Research Unit combines expertise in
(1) infectiology of medically important pathogens (measles virus (MV), Neisseria meningitidis, Neisseria gonorrhoeae and Mycobacterium tuberculosis),
(2) sphingolipid biology in infectious viral and bacterial disease pathogenesis, and
(3) T cell biology and immunotherapy and macrophage biology.
The Research Unit benefits from a technical platform providing highly advanced, novel approaches for spatial resolution of sphingolipids in fixed and in living cells approaching virtually molecular scale and lipidomics.

• DFG Programme: Research Units

Projects

• Analysis of the functional relevance of sphingomyelinases and ceramide in meningococcal pathogenesis (Applicants Sauer, Markus ;  Schubert-Unkmeir, Alexandra )
• Central project of the FOR 2123 Sphingolipid metabolic pathways in infection control by the use of chemically synthesized modified sphingolipids and in the era of sphingolipidomics (Applicants Kleuser, Burkhard ;  Seibel, Jürgen )
• Coating of endotracheal tubes with sphingosine to prevent bacterial growth and ventilator-associated pneumonia (Applicants Gulbins, Erich ;  Seibel, Jürgen )
• Coordination Funds (Applicant Schneider-Schaulies, Sibylle )
• Role of neutral sphingomyelinase in mycobacterial infections (Applicants Grassmé, Heike ;  Gulbins, Erich )
• Role of sphingolipids in the regulation of anti-viral T cell responses (Applicants Beyersdorf, Niklas ;  Schneider-Schaulies, Jürgen )
• Role of the acid sphingomyelinase/ceramide system in lung edema induced by Staphylococcus aureus toxin (Applicants Fraunholz, Martin J. ;  Gulbins, Erich )
• Sphingolipids in gonococcal infection (Applicant Rudel, Thomas )
• Sphingolipids in gonococcal infection (Applicant Rudel, Thomas )
• Sphingomyelinase activation in T cells: Implications for T cell activation and paralysis (Applicant Schneider-Schaulies, Sibylle )

• Spokesperson: Professorin Dr. Sibylle Schneider-Schaulies