Slmb蛋白的棕榈酰化修饰对果蝇Imd通路免疫应答的调节机制研究

脂代谢与天然免疫应答调控之间存在着密切的联系，然而，连接这两个生物学过程的桥梁仍然不清楚。有证据表明，脂代谢过程中的活性代谢物棕榈酸可以通过蛋白质棕榈酰化修饰途径参与调控免疫细胞的功能。棕榈酰化修饰蛋白质学和体外实验证实果蝇天然免疫信号通路Imd通路的负调控因子Slmb蛋白存在棕榈酰化修饰，感染后Slmb的棕榈酰修饰水平下降。由此我们提出假说：脂代谢通过调节Slmb的棕榈酰化修饰参与对天然免疫应答的调控。本项目将利用分子生物学、细胞生物学、遗传学、免疫学以及基因编辑等技术手段确定Slmb发生棕榈酰化修饰的位点及负责修饰的酶，解析棕榈酰化修饰影响Slmb蛋白功能的分子机制，进而阐明脂代谢通过调节Slmb的棕榈酰化修饰参与天然免疫应答调控的分子机制，将有助于加深人们对于脂代谢和天然免疫应答调控之间的联系的认识和理解。

Lipid metabolism is tightly associated with innate immune response, but the molecular bridge between them is still largely unknown. Emerging evidence indicates that palmitic acid, one of active metabolites produced during lipid metabolism, regulates innate immune response through protein palmitylation. Palmitoylome profiling and acyl-RAC demonstrate that, Slmb, a negative regulator of Imd signaling pathway in Drosophila, is palmitoylated.And Bacterial infection decreases Slmb palmitoylation level. Thus, we propose that Slmb palmitoylation is a potential molecular bridge between lipid metabolism and innate immune response. In this proposal, taking advantage of molecular biology, cell biology, genetics, immunology and gene editing tools, we aim to determine the modification site(s) and enzyme(s) that are responsible for Slmb palmitoylation, and how palmitoylation regulates Slmb functions, thus illuminate the molecular mechanism how lipid metabolism regulates innate immune response through Slmb palmitoylation. This study will help deepen our understanding of the relationship between lipid metabolism and innate immune response regulation.