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Innate Immunity for Bacteria Against Phage

Wednesday, March 17, 2021 - 3:00pm to 4:00pm

Speaker

Michael Laub, Ph.D.
Professor of Biology
Massachusetts Institute of Technology

Dr. Laub is a professor of biology at the Massachusetts Institutes of Technology and a Howard Hughes Medical Institute investigator. His lab studies the biological mechanisms and evolution of how cells process information to regulate their own growth and proliferation. Using bacteria as a model organism, the lab seeks to understand the selective pressures and mechanisms that drive the evolution of signaling pathways. His lab has a long-standing interest in the signaling pathways and regulatory networks that enable bacteria to sense and respond to their environments. Most recently, we have focused on toxin-antitoxin systems, which are abundant, but still poorly understood genetic modules found throughout the bacterial kingdom. They study the mechanisms of action of the toxins, the coevolution of toxins and antitoxins, and the role of toxin-antitoxin systems in providing bacteria immunity to some classes of bacteriophage, which will be the topic of his seminar.

Summary

Toxin-antitoxin (TA) systems are ubiquitous genetic elements in bacterial genomes, but their functions are poorly understood and even controversial. To better understand these systems, we developed an RNA-seq-based method for sensitively probing their activities in vivo. Using this method, we find no compelling evidence to support the purported role of TA systems as stress-response modules, despite their strong transcriptional induction following stress. Instead, we find that some TA systems provide potent protection against bacteriophage. In contrast to defense systems like CRISPR and restriction-modification, TA systems must be tightly regulated and switched on rapidly following phage infection. I will present our in-depth study of how one TA system, called toxIN, is specifically activated by T4 phage, as well as insights into how this TA system ultimately disrupts phage development. I will conclude with a broader discussion of the notion that TA systems may represent a major, but underappreciated, component of bacterial innate immunity against their ubiquitous phage predators.


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