PI: Feng Zhang, Department of Brain and Cognitive Sciences, MIT
PI: Konstantin Severinov, Center for Data-Intensive Biomedicine and Biotechnology, Skoltech
The RNA-guided Cas9 nucleases encoded by Type II CRISPR-Cas systems have revolutionized the field of genome engineering. However, Cas9-based systems currently in use suffer from several serious limitations. The goal of this joint proposal is to discover and characterize new CRISPR-Cas systems that encode single-protein Cas effectors that are either superior or complementary to existing Cas9 effectors. Our objective is to combine high-throughput bioinformatics, microbiology, biochemistry and synthetic biology approaches to i) search for fundamentally new types of CRISPR-Cas systems; ii) validate their defensive function; iii) determine target recognition requirements, and iv) use these systems to develop new tools for biomedicine and biotechnology. CRISPR effector enzymes discovered through this effort will complement and/or surpass existing Cas9-based technologies by being more precise, compact, and robust. Thus, the results of proposed work will significantly expand existing genomic editing toolkit and create a firm basis for systems biology-based practical biomedical and biotechnological applications.