1. The adaptive bacterial immunity CRISPR-Cas systems have revolutionized the field of genomic editing and opened up possibilities for genomic medicine. In collaboration with top laboratories from NIH and MIT we predict and functionally characterize new CRISPR-Cas systems that may have advantages over existing ones in practical application. We also study the biological role of CRISPR-Cas systems, studying how they shape the interaction of bacteria with mobile genetic elements such as bacteriophages and impact bacterial ecology and evolution using a set of advanced biochemical, genetic, biophysical and bioinformatics methods. 1.1 Skotech-MIT NEXT-GENeration grant. Search and Development of New Genome Editing Tools for Biomedicine and Biotechnology. K. Severinov. In this joint project with Feng Zhang lab novel CRISPR-Cas systems are being uncovered by bioinformatics means, validated experimentally, and assessed for genome editing applications.
2. Antibiotic resistance becomes a global healthcare problem that may undermine the humankind ability to control bacterial diseases. We search for new antibiotics by minings available genomic and metagenomic data and validate the prediction, discovering new antibiotics and gene clusters that encode them. We determine the structures of validated compounds, mechanisms of their biosynthesis and action on sensitive cells. The knowledge gained is used to create semisynthetic bioactive compounds that can be developed for practical use in medicine and agriculture.
3. Bacterial viruses, bacteriophages, are most abundant and diverse live objects on our planet. They hold a trove of mechanisms that have been selected by evolution to destroy bacteria. Bacteriophages can also be used directly as antibacterial agents. We identify new bacteriophages from environment, determine their genomic sequences and identify molecular mechanisms that they use to effectively infect bacterial hosts. The knowledge gained produces targets for future development of antibacterial drugs.