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Blake Wiedenheft

The rules of evolution are universal to all of life. Like eukaryotic cells, prokaryotic life must also defend itself against parasitic infection. Historically, our appreciation for the prokaryotic 'immune system' has been limited to restriction/modification systems. However, more recent studies suggest that prokaryotic life may have evolved a more sophisticated RNAi-like immune system. CRISPR elements (Clusters of Regularly Interspaced Short Palindromic Repeats) are common features in prokaryotic genomes and a distinct signature of this system. Upon viral challenge, these repetitive elements readily assimilate snippets of new sequences derived from the virus, which then strongly correlates with a phage-resistance phenotype. Comparative genomic analysis has identified a variable cassette of ~25 gene families that are commonly associated with CRISPRs. Many of these CRISPR associated (cas) genes have recently been assigned putative functional roles analogous to those involved in the eukaryotic RNAi-based gene regulation system. The aim of my research is to biochemically identify and structurally characterize the components of this immune system.

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