Areas of Interest
The problem of organelle biogenesis, and especially the
mechanisms by which individual protein and lipid species are
targeted to specific intracellular membranes, is a major focus
of current research in cellular and molecular biology. This
laboratory is interested in molecular mechanisms of assembly of
the outer membrane of Salmonella typhimurium, with
emphasis on the biogenesis of the complex lipopolysaccharide
which is characteristic of this membranous organelle. Based on
biochemical, genetic and immunoelectron microscopic studies, we
have proposed a mechanism for lipopolysaccharide biogenesis
which involves a complex pathway of vectorial transmembrane
assembly of the molecule across the cytoplasmic membrane,
followed by translocation to the outer membrane. A variety of
molecular genetic and biochemical approaches are now being used
to test this hypothesis and to analyze mechanisms of genetic
regulation of lipopolysaccharide synthesis. Current studies have
as major aims: 1) isolation and characterization of mutants
specifically blocked in translocation of lipopolysaccharide to
outer membrane; and 2) analysis of the mechanism of positive
transcriptional regulation of genes for biosynthesis of
O-antigen chains of lipopolysaccharide and investigation of the
possibility that this transcriptional control system functions
as part of a larger environmentally regulated control circuit.
Selected Publications
McGrath, B.C. and M.J. Osborn (1991) Localization of the
terminal steps of O-antigen synthesis in Salmonella
typhimurium. J. Bacteriol. 173:649-654.
Marino, P.A., B.C. McGrath and M.J. Osborn (1991) Energy
dependence of O-antigen synthesis in Salmonella typhimurium.
J. Bacteriol. 173:3128-3133.
McGrath, B.C. and M.J. Osborn (1991) Evidence for
energy-dependent transposition of core lipopolysaccharide across
the inner membrane of Salmonella typhimurium. J.
Bacteriol. 173:3134-3137.
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