Objective 1: Genetic networks driving host response to major microbial pathogens
WP1 - Identification of pattern recognition receptors for clinically relevant bacterial and fungal pathogens in innate immune cells (macrophages and dendritic cells), and the molecular characterization of signalling components and pathways mediating host immune responses. (Pavel Kovarik, Sylvia Knapp, Karl Kuchler & Wilfried Ellmeier)
WP2 - Identification of cellular targets of a secreted Listeria monocytogenes lipid/tyrosine phosphatase LipA and their roles in regulating virulence of Listeria. (Thomas Decker & Gustav Ammerer)
Objective 2: Identification of overlapping / specific host responses to pathogens
WP3 - The role of Tec family kinases in fungal infections will be deciphered, and we will investigate in vivo responses of Tec-deficient mice to Candida spp infections, including the transcriptomic responses in macrophages and DCs. Further, we will initiate studies on cross-signalling mechanisms linking innate immune cells and dedicated T cell lineages (Tregs, Th1, Th2, Th17) during fungal host dissemination. (Karl Kuchler, Wilfried Ellmeier)
WP4 - In general, using biochemical approaches (semi-quantitative phosphoproteomics) we will attempt to identify shared and specific proteome signatures of relevant intracellular signalling pathways activated by different microbial pathogens (Thomas Decker & Gustav Ammerer, Sylvia Knapp, Pavel Kovarik, Karl Kuchler with Gustav Ammerer)
Objective 3: Quantitative transcriptomics & dynamics of host-microbe interactions
WP5 - A quantitative view of host-microbe interactions, including the dynamics of underlying signaling events in primary immune cells (macrophages & DCs), as well as in pathogens, will be obtained by deep-sequencing of both host and pathogen RNAs; bioinformatics and in silico approaches shall identify regulatory networks required for the host immune response against different microbial pathogens (Karl Kuchler with Arndt von Haeseler).
WP6 - Where unknown, cells and tissues infected by L. monocytogenes in the early phases of intraperitoneal or intragastric infections will be examined in proper animal models. These cells will be subjected to array and RNA-sequencing technology to determine the responses to IFN-I (Thomas Decker with Arndt von Haeseler). The effects of preceding tissue injury on host response to pulmonary pathogens will be studied by sampling cells and tissue from two-hit experiments. Collected cells will be analyzed by micro array +/- RNA sequencing to understand the impact of primary insults (Sylvia Knapp with Arndt von Haeseler).