Joseph Bondy-Denomy

University of California, San Francisco
2019 Scholar

Research Interests

Unlocking Bacterial Immunology to Develop Novel Biotechnology Tools

The microbial world is a fast-paced battlefield. Single-celled microorganisms live in all niches on the planet and face an onslaught from the viruses that infect them, called bacteriophages (phages). My lab studies the immune systems that bacteria use to protect themselves from these parasites. Previously discovered immune pathways in microbes, such as restriction-modification (R-M) and CRISPR-Cas systems have had a massive impact on our understanding of microbial ecology and have been repurposed to generate world-changing biotechnologies.

The rapid rate of evolution at the phage-microbe interface suggests that there is much more innovative and useful biology to discover. We will build a discovery pipeline to identify a new molecular arsenal at the phage-host interface. Researchers have identified many examples of phage proteins that inhibit these immune pathways, called anti-immune proteins. We currently focus on the discovery, evolution, and biochemical characterization of one class of phage proteins, which inhibit CRISPR-Cas. In future work, we will leverage our interest and expertise in phage biology and anti-immune proteins to push our understanding of “bacterial immunology” forward. By utilizing the genomic connections between inhibitors of known bacterial immune systems, we seek to discover novel inhibitors of novel immunity pathways. These findings will provide insights into biological “arms races” and hold the promise to develop new, unanticipated research tools. 

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