Structural mechanisms of bacteriophage infection and assembly

University Of Massachusetts Medical School, Worcester MA

Investigators

Abstract

Bacteriophages (phages), viruses that attack bacteria, have been used to combat antibiotic resistance, design vaccines, and prevent contamination of food and water. Phage particles are complicated structures that are generated through a series of steps. Importantly, phage particles assemble in bacterial hosts that attempt to block phage growth. The mechanisms involved in phage assembly and simultaneous avoidance of bacterial defenses remain to be elucidated. This project will advance understanding of virus-host interactions, promote development of effective antiviral strategies, improve vaccine design, and leverage other phage-related applications. During this project, training and mentorship opportunities for local high school students will be provided, both for Science Fair projects and performing research into phage assembly and infection in the laboratory. The thermophilic phage P74-26, which has the longest tail of any known virus, will be used as a model system for investigating phage assembly. A combination of structural biology, genetic manipulation, and kinetic analyses will be used to identify and characterize assembly pathways in unprecedented detail. This project will focus on three separate aspects of phage life cycle: virus assembly, cellular attachment, and infection. The project aims to elucidate how capsids assemble into topologically linked structures, investigate the mechanism of tail tube polymerization, and determine what phage components participate in bacterial host recognition. In addition, the project seeks to establish how phage genomes cross the bacterial periplasm, investigate the formation of intracellular phage vesicles, and elucidate mechanisms involved in phage assembly inside bacterial cells. The results of this work will form the bedrock for engineering viral components to create novel nanomaterials and reveal how phage evade bacterial defense systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.