Impact of proteostasis and the ubiquitin proteasome system on myeloid cell function in the CNS (A04)

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During innate immune responses, proteostasis is severely challenged by inflammatory damage. Therefore, a well-adapted clearance capacity for damaged proteins by the ubiquitin proteasom system (UPS) is pivotal for myeloid cells to cope with such situations. Proteasome dysfunction can cause autoinflammation with a significant interferon signature. This project aims to investigate the role of the UPS for gene expression programs and microglia cell function under physiological and pathological conditions in vitro, ex vivo and in vivo. Another major objective is the elucidation of the signaling pathway leading from damaged protein to an IFN-response in molecular detail.