Physical and functional map of the virus-induced Toll-like receptor signalling pathways

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Signal transduction pathways are modular composites of interdependent sets of proteins that act in a coordinated fashion to transform environmental clues into a phenotypic response. Recent advances in protein purification and protein mass spectrometry have enabled the systematic analysis of signal transduction pathways by pathway proteomics. Unlike earlier approaches, the pathway proteomics approach allows for the unbiased and comprehensive investigation of protein-protein-interactions in a given pathway, thereby enabling the re-construction of a coherent map of the pathway and setting the ground for a more ¿systems biology¿ understanding of the process. Viral infections continue to threaten human health. Although viruses are seemingly simple, antiviral therapies are by and large unavailable. Innate immunity to viral infection is triggered by conserved molecular patterns such as single- or double-stranded RNA. Those patterns are recognized by distinct Toll-like receptors (TLRs) that initiate the production of type-I interferons, thereby establishing an antiviral condition. The goal of this project is to apply modern pathway proteomics technology to obtain a physical and functional map of the TLR signalling pathways that trigger interferon production upon viral infection.