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Proposing Institution

Computational Biology Friedrich Alexander Universität Erlangen
Project Manager

Prof. Rainer Böckmann
Staudtstraße 5
91058 Erlangen
Recognition of antigen by Dendritic cell (DC) receptors is crucial to the adaptive immune response and, ultimately, for defending the body from foreign pathogens. DC receptor activation is postulated to be regulated by their spatial organization on the plasma membrane. In particular, the signal transduction by the receptors was hypothesized to be regulated by their association with liquid-ordered phase-separated domains enriched in specific plasma membrane lipids and proteins.Exploiting this concept, we study an important class of DC receptors, the so-called C-type Lectin Receptors (CLRs). These were experimentally shown to associate to different membrane microdomains, suggesting a coupling of immune response to the association to different lipid microdomains. It is unknown how the receptor transmembrane domain and the membrane composition affect the observed lateral segregation.In this project, we propose to use extensive all-atom molecular dynamics simulations and umbrella sampling calculations to study the molecular interactions and partitioning of three C-type Lectin Receptors embedded in a heterogeneous model membrane with coexisting liquid-ordered and liquid-disordered lipid domains. The key objective is to provide a molecular view on the lateral sorting of the studied receptors. We expect an unprecedented insight into the underlying driving forces mediating receptor compartmentalization, thereby providing key knowledge for novel immunotherapeutic approaches.

Impressum, Conny Wendler