Innate Immune Signalling Pathways in Mammalian Cells

Innate Immune Signalling Pathways in Mammalian Cells

Cells of the innate immune system are activated by signalling pathways, which can lead to the production of inflammatory cytokines, cell differentiation, and target cell killing. Key components of signalling pathways including the Toll-like receptor pathway are often conserved in invertebrates and mammals. Our project aims at the identification of novel molecules, which mediate target cell killing, myeloid cell differentiation, and the production of inflammatory cytokines. We are focussing on signalling pathways involving the ITAM (Immunoreceptor Tyrosine-based Activation Motif) containing adapter DAP12 and the PI3 kinase recruiting adapter DAP10. We are currently refining methods of retroviral expression cloning using functional read-outs to discover key-players in these pathways. Furthermore, we attempt to identify molecules in these pathways, which are modified by post-translational changes, such as phosphorylation or ubiquitination. The molecules originating from the screens will be validated by gene over-expression and gene knock-down in primary immune cells and in in vivo mouse models. These studies have the potential to develop strategies to amplify innate immune responses against tumors.

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