CRISPR Adaptation - the basis for prokaryotic adaptive immunity

CRISPR适应——原核生物适应性免疫的基础

• 批准号: BB/M021017/1
• 负责人: Malcolm White
• 金额: $ 44.72万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM021017%2F1
• 关键词: CRISPR; Adaptation; basis; prokaryotic; adaptive

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.

CRISPR系统是微生物中的一种适应性免疫系统，可防御病毒感染。由宿主基因组编码的小CRISPR RNA被加载到效应复合物中，并用于检测和破坏具有相似序列的入侵病毒。这种可编程的“寻找和破坏”系统最近被用来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，通过该机制，这些DNA物种被捕获并整合到宿主基因组的正确位置。人们对适应的了解非常少，几乎没有可用的机制细节。在这个项目中，白色（圣安德鲁斯）和博尔特（诺丁汉）实验室将联合收割机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，突出适应途径的一些关键方面。这项工作将导致对适应过程的基本新见解，并为该系统的生物技术应用铺平道路。

项目成果

Prespacer processing and specific integration in a Type I-A CRISPR system.

• DOI: 10.1093/nar/gkx1232
• 发表时间: 2018-02-16
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Rollie C;Graham S;Rouillon C;White MF
• 通讯作者: White MF

Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate.

• DOI: 10.1038/s41586-018-0557-5
• 发表时间: 2018-10
• 期刊: Nature
• 影响因子: 64.8
• 作者: Athukoralage JS;Rouillon C;Graham S;Grüschow S;White MF
• 通讯作者: White MF

DNA-Interacting Characteristics of the Archaeal Rudiviral Protein SIRV2_Gp1.

• DOI: 10.3390/v9070190
• 发表时间: 2017-07-18
• 期刊: Viruses
• 作者: Peeters E;Boon M;Rollie C;Willaert RG;Voet M;White MF;Prangishvili D;Lavigne R;Quax TEF
• 通讯作者: Quax TEF

Control of cyclic oligoadenylate synthesis in a type III CRISPR system.

• DOI: 10.7554/elife.36734
• 发表时间: 2018-07-02
• 期刊: eLife
• 影响因子: 7.7
• 作者: Rouillon C;Athukoralage JS;Graham S;Grüschow S;White MF
• 通讯作者: White MF