扩展时空超分辨成像方法以研究CTP合成酶形成细胞蛇的动态机制

别名“细胞蛇”的CTP合成酶（CtpS）多聚体在近期被发现为一种新型的胞器并得到广泛关注。CtpS作为一种功能重要的蛋白，其产物CTP既是核酸大分子的原料，又是生物膜磷脂分子合成的关键前体；而CtpS也是各种癌症和寄生虫病的药物开发的标靶之一。细胞蛇的形成与CtpS酶活性调控机制密切相关。本课题我们拟通过发展基于荧光超分辨显微技术的光子信息统计算法，获得细胞蛇自组装过程的实时动态高分辨图像。这种新形态的成像技术，将现有的超分辨成像空间与时间解析度向前推进，适用于细胞蛇以及与其形态类似的多种蛋白质纤维状聚合体的动态观测与研究。本研究的成果既能对以CtpS为标靶的各类药物设计提供新的指导，又为其它生物大分子多聚体动态研究提供了新的研究工具，可为相关具有应用价值的生物医学关键问题提供解答。

Polymerization of CTP synthase (CtpS) has been observed recently, and soon becomes a field of intense researches. The polymers of CtpS are termed “Cytoophidia”. CtpS is an important enzyme because its product, CTP, is not only one of building blocks for DNA and RNA, but also involves in the synthesis of almost all membrane phospholipids. More importantly, CtpS has been utilized as a potential drug target for several cancers and parasitic diseases. Little is known about cytoophidia except that the polymerization is closely related to the regulation of CtpS enzymatic activity. In this proposal, we aim to obtain real-time video of the polymerization of cytoophidia with high spatial and temporal resolution. By developing new photon statistics algorithm based on single-molecule fluorescence superresolution microscopy, we will push the envelope for higher spatial and temporal resolution of fluorescence microscopy. Such study can help us illuminate the detailed mechanisms of Cytoophidia. The results of this project can provide guidance for drug design and offer new tools for dynamic study of other biological polymers.