CRISPR Adaptation - the basis for prokaryotic adaptive immunity

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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.