Mechanism of Acquired Immunity in Bacteria

细菌使用称为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记住，检测和摧毁病毒，使用可编程的蛋白质，可以直接攻击任何病毒。该项目的目标是确定这些免疫系统如何发挥作用，并培养学生成为未来的教育工作者和科学研究人员。了解CRISPR系统如何能够靶向和破坏外源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各种机制提供帮助。此外，CRISPR系统的机械解剖使CRISPR衍生的分子机制能够在哺乳动物、植物和细菌中作为强大的基因组编辑技术加以利用。通过应用结构生物学和酶学方法，该项目将继续并扩展NSF资助的高产研究计划，以确定细菌如何将新序列整合到CRISPR基因组位点中，以及如何使用来自CRISPR的小RNA来识别和沉默外源遗传元件。该项目的成果将扩展基础知识，并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见解。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.