Sphingolipid dynamics in infection control
Lipid ordered membrane microdomains enriched for sphingomyelin and sterols are believed to serve as platforms compartimentalizing membrane associated proteins such as receptors and membrane-proximal signaling components, and regulating processes involved in cytoskeletal dynamics. As major membrane components, sphingolipids and their ceramide metabolites play a key role in the dynamics of activated membrane microdomains. These are implicated in steps decisive for the interaction of a host cell with pathogens such as attachment, entry or invasion, intracellular trafficking, compartimentalization and regulation of cell autonomous defense responses. 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.
To address this particular subject in relevant experimental systems, the research unit (FOR) is unique in combining outstanding expertise in
- infectiology of medically important pathogens (measles virus (MV) S. Schneider-Schaulies, Müller (P01); Beyersdorf, J. Schneider-Schaulies (P02)), Neisseria meningitidis (Schubert-Unkmeir (P03)), Neisseria gonorrhoeae (Rudel (P04)), Mycobacterium tuberculosis (Grassmé, Gulbins (P05)),
- sphingolipid biology in infectious viral and bacterial disease pathogenesis (Grassmé, Gulbins (P05), S. Schneider-Schaulies, Müller (P01))
- T cell biology and immunotherapy (S. Schneider-Schaulies, Müller (P01), Beyersdorf, J. Schneider-Schaulies (P02)) and macrophage biology (Grassmé, Gulbins (P05)).
As core topical elements, the FOR will focus on the regulatory role of sphingolipid dynamics both at the host and pathogen level in addressing
- adhesion, activation, differentiation and effector functions of T cells at a molecular (Schneider-Schaulies, Müller (P01)) and cellular level as well as experimental infection models (Beyersdorf, Schneider-Schaulies (P02))
- pathogen adhesion and invasion, trafficking and modulation of host cell functions essential in the control of bacterial pathogens (Schubert-Unkmeir (P03), Rudel (P04), Grassmé, Gulbins (P05)).
The inclusion of the Z01 Project enables the FOR to study sphinglipid biology infections with highly advanced, novel approaches for spatial resolution in fixed and so far even unmatched resolution in living cells approaching virtually molecular scale.