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Bacteriophage biology, genomics, and genome evolution

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Bacteriophage biology, genomics, and the evolution of phage genomes

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Project Description:

A bacteriophage, or more simply phage, is a virus that infects bacterial cells. Mycobacteriophages are phages that infect the bacterial genus, Mycobacterium. Research in my lab is focused on understanding basic mycobacteriophage biology and more broadly, phage genome evolution. I have multiple projects ongoing: 1) Investigating the biology of a subset (Cluster K group) of mycobacteriophages known for their general ability to infect a broad range of mycobacterial hosts, often including the pathogen, M. tuberculosis. We are investigating growth features of Cluster K1 phages that may relate to differences in host preference. Our current findings suggest a subset of K1 mycobacteriophage are optimized for growth at lower temperatures, which may be an adaptation for better survival an environment with low host density. We believe there is a link between these growth features and the ability of cluster K mycobacteriophages to recognize a broader range of hosts. This project is near completion. 2) Investigating phage genome evolution. This project seeks to better understand the similarities and differences in genome structure and gene content across known mycobacteriophages, and to address questions on the nature and function of the evolutionary mechanisms that generate the observed genome architecture and genetic diversity. To address these questions, we have designed, constructed, and are testing pairs of modified phage genomes, that differ in the presence/absence of specific coding information, for impacts on phage growth using a variety of different assays. This work may help us understand how genetic diversity, prevalent in phage genomes, is generated, as well as better understand the modular nature of phage genomes. 3) Investigating how mycobacteriophages recognize and initiate infection of a mycobacterial host. This proess (infection initiation) is defined by the sequence of steps: 1) reversible binding of phage to host, 2) irreversibly binding to host cells, and 3) transfer of phage DNA into host cells. It is a goal of this work to better understand the roles of phage receptor binding proteins and corresponding host receptor components in driving the phage infection initiation process. Our findings will provide new and important information on the molecular biology of phage-host cell interactions from mycobacterial host selection through mycobacteriophage infection and a better understanding of the evolution of mycobacteriophage genomes. All research projects employ a combination of microbiological, molecular, biochemical and bioinformatic methods of analyses. These opportunities are open to Hope College students only.

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