Kevin Forsberg 

University of Texas Southwestern Medical Center
2022 Scholar

Research Interests

The mysterious origins of anti-CRISPR proteins

The Forsberg lab studies bacteria and their viruses, called phages, which have been locked in battle for billions of years. To prevent infection, bacteria have invented a diverse array of anti-phage defenses, many of which have not been discovered. In response, phages have devised myriad counter-defenses to overcome bacterial immunity and re-establish infection. Because most phage counter-defenses are also undescribed, phage infection outcomes are difficult to predict, and their impacts are hard to control. This has major consequences. Phages can convert innocuous bacteria into dangerous pathogens, are used to treat infectious disease, and are emerging as important tools for modifying microbiome function. To better understand this age-old conflict, the Forsberg lab is identifying new defense and counter-defense systems, learning how they function, and figuring out how they evolve.

Functional selections are an important tool for the Forsberg lab in our discovery efforts. This approach uses a survival phenotype to identify genes with desired activities from enormous DNA libraries. Because phage infections are life-or-death scenarios for both the viruses and bacteria involved, functional selections are well suited to find new genes involved in this conflict. The right gene, at the right time, can make all the difference. This approach is especially useful for studying phage and bacterial genes, as their functions are often unrecognizable from sequence alone, making it difficult to predict their activities using computational methods. Previously described defense and counter-defense systems have become ubiquitous tools in molecular biology and are increasingly recognized as the evolutionary antecedents to many eukaryotic innate immune factors. Thus, by finding new examples of these systems, we can not only improve predictions of phage infection outcomes, but also uncover new tools for molecular biology and reveal the evolutionary origins of eukaryotic immune factors.

Of course, gene discovery is just the beginning. Aware of this, the lab also combines microbiology, genetics, and biochemistry to probe the mechanistic underpinnings and evolutionary implications of the genes in our selections. Our strategy is to cast a wide net to identify interesting new functions and then dive deeply into the details of our most interesting discoveries. And because phages and bacteria are the most abundant biological entities on earth, with the longest-running evolutionary arms race in the biosphere, any discoveries we make today are certain to just scratch the surface of what truly exists in nature!

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