Faculty Highlight: Jason Peters – New tools and questions for high-throughput bacterial genomics

By Victoria Rubinetti

Jason Peters, currently an Assistant Professor in the School of Pharmacy, has seen the spectrum of UW-Madison life. He received his PhD in the Genetics PhD program at UW-Madison where he studied the fundamentals of bacterial transcription under Bob Landick. He took some time away for postdoctoral training at the University of California, San Francisco under Carol Gross, where he developed some of the first high-throughput screening approaches using then-revolutionary CRISPR methods, before returning to UW-Madison as a faculty member. 

Dr. Peters’ research is probing the essential roles of bacterial genes to address two pressing challenges. On one hand, his team investigates antibiotic-resistant bacteria by identifying the genes that are most critical for their growth under stress imposed by antibiotic treatments. These genes represent promising therapeutic targets, since disabling them could compromise the bacterium’s ability to thrive during infection. On the other hand, his tools applied to industrial microbes are helping to improve their tolerance of industrial stressors. Engineering cells for improved tolerance means more of cell efforts can go toward making bioproducts, improving the economics of those processes.  

Jason Peters

“Although these two subjects may initially seem quite different,” Peters says, “they are similar in that improving treatment efficacy for antibiotic- resistant bacteria and more economical bioproduct generation can be achieved by understanding the functions of bacterial genes.” 

Both approaches leverage CRISPR-based mutation to probe many mutants in high throughput.    

We asked Dr. Peters some questions about his research and trajectory. 

What are the big-picture questions and significance of your research?

Gene products may serve as therapeutic targets for inhibition in the case of antibiotic-resistant bacteria, or as engineering targets to improve resilience to harsh production stresses that would otherwise decrease bioproduct yields. To understand which genes may be important targets, we take an open-ended approach that perturbs all genes in the genome (generally as a pool of strains with one gene perturbation per strain) and asks which genes are critical for growth under a given condition. For antibiotic-resistant bacteria, we want to know which genes the bacterium depends on the most during normal growth, as these genes will be the best targets for treating infections. Identifying genes required for growth in antibiotics improves our understanding of antibiotic resistance mechanisms and may facilitate improved diagnostic approaches. For bioproduct-relevant bacteria, uncovering genes that underpin tolerance to plant-derived inhibitors facilitates genetic engineering to increase production strain resilience.  

What technologies do you focus on?

The technology we use to perturb genes is derived from bacterial adaptive immune systems known as CRISPR-Cas. Variations of CRISPR technology we and others have developed allow us to reduce or increase the amount of specific gene products in bacterial cells, often with a high degree of precision and predictability. Our ethos is that CRISPR genetic tools we develop should be applicable to an evolutionarily broad set of bacteria and available for use by the community. 

Has there been a single person, event, or experience that most influenced your trajectory to where you are today?

No, training scientists is done by a community. That said, the individuals who have contributed the most to my scientific career are Bob [Landick] and Carol [Gross]. 

Is there anything else you’d like to introduce about yourself, your background, or your research interests?

I’m a great person to contact for students interested in graduate work at UW-Madison as I’ve seen the university from multiple angles – first as a CALS graduate student and now as a School of Pharmacy professor – and through my affiliations with several graduate programs and departments.  

 

Lastly, Peters has not only contributed to UW-Madison academically, but creatively as well. “I am very likely the only professor on campus to win costume contests in two UW-Madison Schools (in 2008 in the Biochemistry costume contest within CALS and in 2019 in the School of Pharmacy costume contest).”