CRISPR Adaptation - the basis for prokaryotic adaptive immunity

CRISPR系统是微生物的适应性免疫系统，可以抵御病毒感染。宿主基因组编码的小CRISPR rna被装载到效应复合物中，用于检测和摧毁具有相似序列的入侵病毒。这种可编程的“寻找和破坏”系统最近被用于指导包括人类细胞在内的许多生物体中特定基因靶点的切割，并在基因组工程和医疗保健中显示出巨大的前景。CRISPR系统的基础是捕获来自入侵病毒的小DNA片段库。该项目的重点是“适应”机制，通过这种机制，这些DNA物种被捕获并整合到宿主基因组的正确位置。人们对适应的了解很少，几乎没有机制细节。在这个项目中，怀特（圣安德鲁斯）和博尔特（诺丁汉）实验室将结合他们在生物化学和遗传学方面的专业知识来解决这个重要的问题。这项工作将利用两个实验室最近的一些突破，这些突破突出了适应途径的一些关键方面。这项工作将导致对适应过程产生根本性的新见解，并为该系统的生物技术应用铺平道路。

The CRISPR system is an adaptive immune system in microbes, providing defence against viral infection. Small CRISPR RNAs encoded by the host genome are loaded into Effector complexes and used to detect and destroy invading viruses with similar sequences. This programmable "seek and destroy" system has recently been harnessed to direct the cleavage of specific gene targets in many organisms including human cells, and shows great promise in genome engineering and healthcare. The underlying basis for the CRISPR system is the capture of a library of small DNA fragments derived from invading viruses. The focus of this project is on the mechanism of "Adaptation", by which these DNA species are captured and integrated in the correct position in the host genome. Adaptation is very poorly understood with little mechanistic detail available. In this project the White (St Andrews) and Bolt (Nottingham) labs will combine their expertise in biochemistry and genetics to tackle this important question. The work will capitalise on some recent breakthroughs by both labs that highlight some key aspects of the Adaptation pathway. The work will lead to fundamental new insights into the Adaptation process and also pave the way towards biotechnological applications of the system.