To survive in the face of perpetual phage attacks, bacteria and archaea have developed a variety of anti-phage defense systems, commonly known as the microbial “immune system". These systems play a major role in shaping the evolution of both phage and bacterial genomes. In the past, the discovery of new defense systems contributed not only to our understanding of the arms race between bacteria and phage, but also provided important molecular tools that proved invaluable for biotechnological utilizations. Defense systems, including CRISPR-Cas and Abi systems, are being used in the dairy industry to protect cheese- and yogurt-producing bacteria against detrimental phage attacks. Moreover, deep mechanistic understanding of the mode of action of individual systems has led to revolutions in molecular biology, as demonstrated by the utilization of restriction enzymes for genetic engineering, and the adaptation of the CRISPR-Cas system into powerful genome editing tools.
The objective of this project is to understand the arsenal of defense mechanisms that are at the disposal of bacteria in their struggle against phages, their evolutionary implications, and the ways by which phages counteract these defenses. The project includes extensive mechanistic characterization of individual defense systems, together with broad mapping of new defense systems within microbial genomes and metagenomes. The project also aims to mine phage genomes to identify phage-encoded inhibitors of bacterial defenses, which will further assist in understanding the mechanism of defense for the systems we discover.
Importance for society: Past discoveries of novel defense systems led to revolutions in molecular biology, because defense systems entail specific molecular recognition and targeting characteristics. Discovery of novel defense systems and understanding their mechanism of action could lead to the development of additional strong molecular tools that would be beneficial to the broad scientific community. Moreover, understanding of bacterial immunity can lead to better understanding of our own immune system.
