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Dr. Silverman:

Dr. Silverman 101
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Dr. Silverman's CV in brief

Publications

Genetic Models of Disease Research Program

Philip M. Silverman, Ph.D. Member, Genetic Models of Disease Research Program Marjorie Nichlos Chair in Medical Research Professor of Botany/Microbiology, University of Oklahoma Adjunct Professor, Department of Cell Biology, University of Oklahoma Health   Sciences Center

Research Interests
My research focuses on structural and mechanistic aspects of horizontal DNA transfer among bacterial cells, using F+ strains of Escherichia coli as a model system. Horizontal DNA transfer and related phenomena play an essential role in the virulence of numerous human pathogens and constitute a powerful driver of adaptive change within and among bacterial populations, notably in the spread of antibiotic resistance.

Using a combination of approaches, my laboratory has over the past few years defined groups of interacting proteins that form the surface complexes that mediate horizontal DNA transfer. Most of these proteins are required for the elaboration of F-pili, extracellular filaments that mediate the early stages of conjugal DNA transfer. Conjugative pili also serve as adsorption organelles for both RNA and DNA bacteriophages. They are composed of a helical arrangement of a single subunit, F-pilin. Our studies over the past year have been directed at the structure and assembly of F-pili.

We have made three important advances. First, we developed a rapid, quantitative assay for F-pili based on the specific lateral adsorption to F-pili of the icosohedral RNA bacteriophage R17. By immunofluorescence microscopy, R17 particles conjugated with a fluorescent dye and bound to F-pili formed fluorescent filaments; F-pili attached to cells and free F-pili were both visible by this method. Cell-bound bacteriophage were separated from free bacteriophage particles and quantitated by fluorometry. We are now applying these assays to study the genetics and physiology of F-pilus formation.

The second advance, a collaborative study with Dr. Ed Egelman of the University of Virginia, concerns the structure of F-pili. Using single-molecule, real space reconstruction from electron micrographs of purified F-pili, Dr. Egelman has acquired reliable structural data at 10 angstrom resolution. These data have led to a novel hypothesis for the conformation of the F-pilin subunit in the filament, which we are now testing.

The third advance has been the development of a novel biochemical strategy for isolating the protein complexes that mediate F-pilus assembly. This strategy will enable biochemical and structural analyses of these complexes not heretofore possible.

Joined OMRF Scientific Staff in 1988.

Mailing Address
Genetic Models of Disease Research Program, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-7660
Fax: (405) 271-7312
E-mail: Philip-Silverman@omrf.org