Genetic and evolutionary study of bacteria-jumbophage interactions

We investigate the genetics and evolution of the interaction between bacteria and jumbophages.

Jumbophage phiKZ under Electron Microscope (Sokolova et al., Virology, 2014)

Phages are viruses that only attack bacteria. Jumbophages are a unique group of phages that possess exceptionally large genomes and eukaryote-like properties. We study the interactions and co-evolution of jumbophages and their host bacteria.

Phages are the most abundant and diverse bio-entities on our planet and are found everywhere from the human gut to the global ocean. The concept that phages are small and simple viruses has been challenged by the discovery of jumbophages. With a big genome size, jumbophages often carry distinct genetic repertoires and possess fascinating “eukaryote-like” properties. We study the largely untapped biology of jumbophages and explore their potential in curbing the bacterial antimicrobial resistance crisis.

Jumbophages and the jumbophage-killer immune systems
The Pseudomonas phage phiKZ is a model jumbophage infecting the bacteria Pseudomonas aeruginosa. Upon infection, phiKZ forms an early phage infection vesicle enclosing the injected phage genome. As infection progresses, phiKZ assembles a nascent phage “nucleus” in the bacterial cell to shield its genome from all DNA-targeting immune systems of bacteria. We discovered that bacteria have evolved defense systems targeting the unique biology of jumbophages. Our group studies the “jumbophage killer system” (Juk), a family of widespread immune systems across bacterial phyla specifically blocking phiKZ-like jumbophages.

Studying phiKZ infection and Juk immunity
We will use a suite of techniques, including genetics, microscopy, biochemistry, and structural biology to characterize how the diverse Juk effectors abort phiKZ infection and to identify how phages can overcome Juk immunity. Lastly, we will couple high-throughput sequencing with mathematical modeling to characterize the evolutionary dynamics between bacteria and jumbophages in both laboratory conditions and natural settings.

Fighting antibiotic-resistant bacteria with jumbophages
The largely untapped biology of jumbophages promises breakthroughs in basic biology and will likely lead to revolutionary genetic innovations. Furthermore, jumbophages often kill a large number of isolates of a given bacterial species, making them promising allies in our fight against drug-resistant bacteria.

The research group led by Yuping Li will be starting in October 2024.