Beisel Group – Bacterial Immune Systems

Bacteria have been locked in an intense arms race with their viruses, bacteriophages, for billions of years and covering every habitable niche of our planet. This race has prompted bacteria to evolve diverse and sophisticated immune systems to effectively recognize and combat bacteriophages. While the underlying properties of these immune systems are geared toward allowing bacteria to maintain the upper hand against their bacteriophage foes, they also represent powerful functionalities we can use for our purposes.

Two important examples are restriction-modifications, which contain the restriction enzymes that drove the recombinant DNA revolution in the 1970's, and CRISPR-Cas systems, the source of CRISPR technologies driving modern revolutions in gene editing and gene therapies. At the same time, these two examples represent the tip of the iceberg, with hundreds to thousands of new bacterial immune systems awaiting characterization. In turn, further efforts to characterize and harness these systems could drive the next revolutions in biotechnology and human health.

Research Focus

The Beisel group is devoted to the broad yet growing topic of bacterial immune engineering, where we aim to understand and then harness the rich diversity of immune systems bacteria evolved to thwart infections by bacteriophages.

To date, we have been working in three overlapping areas: developing high-throughput tools to characterize bacterial defenses, exploring the properties and functions of these defenses as well as how bacteriophages fight back, and harnessing these insights to improve the health and well-being of children in low and middle income countries. In the first area, we principally employ cell-free transcription-translation (TXTL) that can produce RNA and protein from DNA constructs in a few hours, allowing us to rapidly and scalably characterize without the need for protein purification and culturing cells. In the second area, we have primarily worked on uncovering new biology within CRISPR-Cas systems, revealing new categories of systems as well as both protein-based and RNA-based means of counter-defense by bacteriophages.

Finally, in the third area, we have been harnessing these discoveries to generate new and improved technologies to benefit humanity. Here, we have developed immune-derived tools for genome editing, molecular diagnostics, and tailored-spectrum antimicrobials to name a few. Our vision is a future in which these tools are part of everyday use that can be implemented in any setting and have a tangible positive impact on health and well-being.