Shiraz Shah:
Characterising the CRISPR immune system in Archaea using genome sequence analysis

Date: 15-09-2012    Supervisor: Roger A. Garrett

Archaea, a group of microorganisms distinct from bacteria and eukaryotes, are equipped with an adaptive immune system called the CRISPR system, which relies on an RNA interference mechanism to combat invading viruses and plasmids. Using a genome sequence analysis approach, the four components of archaeal genomic CRISPR loci were analysed, namely, repeats, spacers, leaders and cas genes. Based on analysis of spacer sequences it was predicted that the immune system combats viruses and plasmids by targeting their DNA. Furthermore, analysis of repeats, leaders and cas genes revealed that CRISPR systems exist as distinct families which have key differences between themselves. Closely related organisms were seen harbouring different CRISPR systems, while some distantly related species carried similar systems, indicating frequent horizontal exchange. Moreover, it was found that cas genes of Type I CRISPR systems could be divided into functionally independent modules which occasionally exchange to form new combinations of Type I systems. Furthermore, Type III systems were found to be genomically associated with various combinations of accessory genes which may play a role in functionally extending the activity of the Type III interference complexes. This dynamic nature of the CRISPR immune systems may be a prerequisite for their continued efficacy against the ever changing threats they protect their hosts from.