Elucidating the molecular foundations of an arms race between two major classes of bacteriophages and their hosts

MIT PI: Michael T. Laub, Department of Biology
SkT PI: Maria L. Sokolova, Center of Life Sciences

There are an estimated 1031 bacteriophages, viral predators of bacteria, on the planet. This includes a huge diversity of phages that live in and on humans, shaping the communities of bacteria that comprise the microbiome, which directly impacts human health and disease. Additionally, phage therapy has emerged as a promising new alternative to traditional small-molecule antibiotics.  Despite the numerical prevalence of phages, their importance to human health, and their therapeutic potential, most phages remain extremely poorly characterized. This project aims to use a combination of powerful new approaches, including Hi-C technology, to probe two important classes of phages, the so-called "jumbo" phages and crAssphages, the latter of which are the most abundant phages of human gut. Specifically, we will: i) Elucidate chromosome organization, DNA replication, and transcription of bacterial host and viral predator during infection by model "jumbo" phages to provide insights needed for rational engineering of them as new antimicrobial agents; ii) Discover new bacterial anti-viral systems and their mechanisms of action to better understand the arms race between bacteria and phages, which drives their co-evolution and which is critical to understand the long-term potential of successful deployment of phages in clinical settings as antimicrobials; iii) Determine the pairwise interactions between bacteria and phages, especially crAssphages, in the human gut and study these interactions in controlled laboratory settings, to inform new approaches for manipulating the composition of the human gut microbiome.

Back to the list >>