Grant: Project Grant

Like humans, bacteria have systems that provide immunity against viral infection. One of the most important and frequently occurring of these systems is called CRISPR-Cas. CRISPR-Cas is a particularly powerful system because it is adaptive in being able to acquire immunity against newly encountered viruses. To survive the existential challenge posed by CRISPR-Cas systems, bacterial viruses have evolved to produce proteins, known as anti-CRISPRs, that inhibit CRISPR-Cas systems. Research described in this grant proposal is directed at understanding the mechanisms by which anti-CRISPRs perform their function. Our studies will also focus the evolution of anti-CRISPRs and how the presence of anti-CRISPRs has driven compensating changes in the CRISPR-Cas systems. This type of "evolutionary arms race" occurs in most host-parasite interactions, including those involving viruses and humans, which provides broad relevance for our work. In addition, CRISPR-Cas systems have been developed into a revolutionary tool for human genome editing, an achievement that was recently honoured with a Nobel Prize. Our work will contribute to understanding how CRISPR-Cas systems function and could aid in improving this important technology. Finally, bacterial viruses are being used as therapeutics to treat antibiotic-resistant bacterial infections. Since CRISPR-Cas systems may prevent the replication of some viruses used for these therapies, arming them with optimal anti-CRISPRs will improve their ability to eradicate infections.