题目：活细胞糖基化修饰调控工具的开发与应用

主讲：葛韵 研究员（深圳湾实验室）

时间：10月31日（周四）11:20-12:20

会议地点：慧园4栋301

报告摘要：

Glycosylation is the most abundant and diverse post-translational modification of proteins, encompassing N-glycosylation, O-GlcNAcylation, and other types. Notably, the nutrient sensor O-GlcNAc is dynamically and reversibly regulated by OGT and OGA to fine-tune protein functions. Current approaches for modulating O-GlcNAc in live cells have limited specificity and spatiotemporal resolution. To address this, we designed a nanobody-directed O-GlcNAc eraser to dissect distinct O-GlcNAc functions on specific substrates through protein engineering. The modularity and specificity of this tool are well demonstrated at the proteome level. Additionally, we utilized a small-molecule responsive intein for controllable activation of OGA in a dose-dependent and spatiotemporally resolved manner, showcasing its potential for tracking O-GlcNAc homeostasis and combinatory cancer therapies. We envision that these tools will achieve precise regulation of O-GlcNAc in live cells, enhancing our understanding of O-GlcNAc functions. Furthermore, we have engineered N-glycosylation on proteins, particularly nanobodies, to confer additional desired functions. We equipped an anti-CD47 nanobody with high-mannose-type N-glycosylation and loaded it onto cancer cell-derived vesicles. In two mouse tumor models, this tripartite ensemble of high-mannose glycan, anti-CD47 nanobody, and cellular vesicles has been validated to significantly activate antitumor immunity and suppress tumor growth. In summary, chemical biology strategies for glycosylation regulation enable us to study and leverage glycan functions in biological processes.

个人简介：

葛韵博士是深圳湾实验室化学生物学研究所特聘研究员，兼任北京大学深圳研究生院博士生导师。国家级青年人才项目获得者，主持国自然面上项目、重大研究计划培育项目等。2018年博士毕业于北京大学，随后在哈佛大学化学与化学生物学系进行博士后研究，2022年加入深圳湾实验室。课题组主要集中于蛋白质糖基化修饰的鉴定、调控工具的开发和修饰功能的研究，并拓展糖修饰在功能分子上的应用。迄今为止以第一/通讯作者身份在Nat. Cell Biol., Nat. Chem. Biol., JACS, Angew等杂志上发表多篇文章，并申请国内外专利若干。