新型抗噬菌体防御系统—RADAR系统的结构与功能研究

为抵抗噬菌体侵染，细菌进化出多样且精巧的抗噬菌体防御系统。基于这些防御系统，人们开发出多种强大的生物学工具，推动了整个生命科学的发展。因此，发掘和解析更多新型抗噬菌体防御系统的作用机制，既可以拓展我们对细菌-噬菌体互作复杂性的认识，又能为设计新型生物学工具提供思路。近期鉴定的抗噬菌体防御系统—RADAR系统，可通过多亚基协同作用，催化特定RNA的腺嘌呤发生脱氨反应，进而导致宿主细胞死亡来阻断噬菌体侵染。该系统的发现也首次表明RNA脱氨酶可以参与细菌-噬菌体博弈。然而，目前对于RADAR系统如何组装、如何进行活性调控以及如何催化底物，都是知之甚少。申请人将在前期研究基础上，综合利用生物化学、结构生物学和细菌生物学等手段，阐明RADAR系统的亚基组装、活性调控和底物催化机制。该研究有助于揭示细菌-噬菌体互作的新颖机制，也有望为基于RADAR系统的工具开发和新型噬菌体疗法设计提供理论基础。

In order to resist phage infection, viruses have evolved various and sophisticated strategies to counteract many of these defense systems. Based on these defense systems, people have developed a variety of powerful molecular biology tools to promote the development of the life science. Discovery and analysis of noval antiphage defense system can not only extend our understanding of the interaction between bacteria and phages，but also provide ideas for the design of new biological tools. The recently identified antiphage defense system-RADAR system, can edits RNA in response to phage infection through the synergistic action of multiple subunits, leading to the death of host cells.These findings also shows for the first time that RNA deaminase can participate in the arms race between bacteria and phages. However, the molecular mechanism of assembly, operation and catalysis of RADAR system is still unclear. Based on the preliminary data, combined with biochemistry, structural biology and bacterial biology, the applicant is committed to study the assembly, catalysis and operation mechanisms of RADAR system.The research will provide new approach to the novel mechanism of bacteria-phage interaction, and also to provide a theoretical basis for the design of molecular biological tools.