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Functional genomics of innate immune pathways in mammalian cells


The innate immune system provides the first line of immune defence against infectious diseases and in the fight against cancer. The direct recognition of bacteria, viruses and cancer cells by innate immune cells is crucial for priming of the adaptive immune response and the establishment of immunological memory.

Innate immune signalling pathways mediated by Toll-like receptors are quite well studied. Little is known about the activation of additional signalling pathways in innate immunity. This project aims at the identification of novel molecules in innate immune pathways in mammalian cells by functional genomics. The focus will be on signalling pathways in myeloid cells involving the Immunoreceptor Tyrosine-based Activation Motif (ITAM) containing adaptor DAP12 and additional innate immune signalling pathways.

These studies will include the identification and investigation of innate immune pathways in response to their natural ligands, bacteria and viruses. Powerful technologies of refined retroviral expression cloning combined with advanced proteomics will be applied to identify novel molecular targets by functional read-outs.

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 increase the basic knowledge in innate immunity and to identify novel drug targets. Molecular targets for agonistic compounds might be identified to provide new anti-viral and anti-bacterial drugs to fight against emerging infectious diseases.

The screens might also discover molecular targets for antagonistic compounds for indications of inflammatory diseases and septic shock syndrome. The scientific expertise of the team leader and excellent facilities at the host organisation including a unit of technology transfer are essential prerequisites for the proposed excellence team 'innate immunity'.

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