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

在先天免疫应答期间，蛋白质稳态受到炎性损伤的严重挑战。因此，泛素蛋白酶体系统（UPS）对受损蛋白的良好适应清除能力对于骨髓细胞科普此类情况至关重要。蛋白酶体功能障碍可引起具有显著干扰素特征的自身炎症。本项目旨在研究UPS在体外、离体和体内生理和病理条件下对基因表达程序和小胶质细胞功能的作用。另一个主要目标是阐明导致从受损蛋白质到IFN-应答的信号通路的分子细节。

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.