David Burstein, Alexander Probst, Karthik Anantharaman, Brian Thomas and Jillian Banfield are co-authors of “New CRISPR-Cas Systems from Uncultivated Microbes.” The research letter came out in the February 9, 2017 issue of Nature.
CRISPR–Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR–Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR–Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, the researchers identify a number of CRISPR–Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR–Cas system. In bacteria, they discovered two previously unknown systems, CRISPR–CasX and CRISPR–CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows the researchers to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.
David Burstein is currently a joint postdoc with Professors Jill Banfield and Jennifer Doudna. He received his doctoral degree at Tel Aviv University, with a dissertation on machine-learning approaches for the identification of pathogenic determinants. Alexander Probst is a postdoctoral researcher in the Berkeley Earth and Planetary Science Department. Karthik Anantharaman is a postdoctoral researcher in the Earth and Planetary Science Department. Brian Thomas is a research staff member in the Banfield Lab.
Jillian Banfield is a geomicrobiologist and biogeochemist whose work focuses on the fundamental relationship between microorganisms and their chemical environments. She is jointly appointed in the Berkeley Earth & Planetary Science and Environmental Science, Policy, and Management Departments and is a recipient of the MacArthur genius grant.
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