Mechanism of Acquired Immunity in Bacteria

细菌使用名为CRISPR的DNA序列，以及CRISPR相关(CAS)蛋白来保护自己免受病毒感染。这些免疫系统使微生物能够使用可编程蛋白质记忆、检测和摧毁病毒，这些蛋白质可以被指示攻击任何病毒。该项目的目标是确定这些免疫系统是如何发挥作用的，并培养未来成为教育工作者和科学研究人员的学生。了解CRISPR系统如何能够靶向和摧毁外来核酸，将为深入了解生命所有领域中RNA控制的基因组调控的不同机制提供深刻的见解。此外，对CRISPR系统的机械解剖使CRISPR衍生的分子机械能够被利用为哺乳动物、植物和细菌中强大的基因组编辑技术。通过应用结构生物学和酶学方法，该项目将继续并扩大一项由NSF资助的高效研究计划，以确定细菌如何将新序列整合到CRISPR基因组座位中，以及来自CRISPR的小RNA如何被用来识别和沉默外来遗传元素。该项目的成果既将扩展基础知识，又将为开发用于基因编辑和基因组操作的新生物技术工具提供洞察力。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Bacteria use DNA sequences called CRISPRs, together with CRISPR-associated (Cas) proteins, to protect themselves from viral infections. These immune systems enable microbes to remember, detect and destroy viruses using programmable proteins that can be directed to attack any virus. The project goals are to determine how these immune systems function and to train students who will become future educators and scientific researchers. Understanding how CRISPR systems are able to target and destroy foreign nucleic acids will provide deep insight into the diverse mechanisms of RNA-controlled genome regulation in all domains of life. In addition, mechanistic dissection of CRISPR systems has enabled CRISPR-derived molecular machinery to be harnessed as powerful genome editing technology in mammals, plants and bacteria. Through application of structural biology and enzymology approaches, this project will continue and extend a highly productive NSF-funded research program to determine how bacteria integrate new sequences into CRISPR genomic loci and how the small RNAs derived from CRISPRs are used to recognize and silence foreign genetic elements. The results of this project will both expand fundamental knowledge and provide insights enabling development of new biotechnological tools for gene editing and genome manipulation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.