This award will support collaborative research in genetics between Dr. Stuart Austin, Advanced Bioscience Laboratories, Inc., Frederick, Maryland and Professor Kurt Nordstrom, Department of Microbiology, University of Uppsala. The objective of the proposed project is a study of the dynamics of plasmid partitioning in bacteria and of partition-specific incompatibility. Low-copy-number plasmids are responsible for many economically important phenomena, such as drug resistance and bacterial pathogenicity. In addition to highly accurate replication controls the plasmids are subject to a partition mechanism that, at least superficially, resembles mitosis in eukaryotic cells. Using components of two model systems, the plasmids R1 and P1 of Escherichia coli, the investigators seek to understand how partition is accomplished, and how the partition systems are integrated into an overall strategy which ensures the remarkable fidelity with which these plasmids are maintained in nature. The collaborative effort will focus on the question of how plasmid copies are recognized for partition and, to this end, will concentrate on studies of the distribution of plasmid copies in situations where two plasmids are competing with each other during key events in the cell-cycle (partition-mediated incompatibility). They will also develop a theoretical treatment of plasmid distribu- tion based on existing and new models for plasmid maintenance and on their detailed knowledge of the characteristics of the replication systems of these plasmids. Dr. Austin and Nordstrom are leading investigators in the field of plasmid biology and their combined expertise is an important factor in the successful outcome of this project. The results of this research are expected to yield data that can significantly advance understanding of the mechanisms of P1 and R1 partitioning.
