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Mechanisms of Plasmid Localization and Segregation

$327,000FY2002BIONSF

University Of California-San Diego, La Jolla CA

Investigators

Abstract

DNA segregation is a fundamental process that is poorly understood in bacteria. Recent work shows that E. coli plasmids are targeted to specific regions within the cell, rather than being randomly distributed in the cytoplasm as long thought. Multicopy plasmids form clusters that are targeted to the cell midpoint where they are duplicated. Following duplication, plasmids migrate with rapid kinetics from midcell to the future midpoints of the nascent daughter cells. Little is known about the mechanisms underlying plasmid localization or movement in bacteria. While a set of par genes important for DNA partitioning have been identified, how they contribute to plasmid localization is not understood. The goal of this study is to identify genes encoded by plasmids and their hosts that are directly responsible for mediating plasmid targeting, clustering and movement. Since bacterial DNA segregation is a fundamental process about which so little is currently known, the impact of this study will be extraordinarily broad, potentially affecting any area of research where bacteria are involved. Some areas that will be impacted include microbial ecology and evolution, pathogenesis, genetics, genomics, and bioremediation. For example, understanding the details of DNA segregation could contribute directly to the development of new antibiotics designed to inhibit the process. Since one of the plasmids used here is a broad host range antibiotic resistance determinant, these studies will also impact our understanding on the evolution and spread of antibiotic resistance. This work will also have a significant impact on undergraduate education by contributing to the training of students in the biological sciences.

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