Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Silhavy, Thomas J.
Location Princeton University
Primary Field Microbial Biology
Secondary Field Genetics
 Election Citation
Silhavy was the first to identify a component of the E. coli protein secretion machinery and the first to describe a "two component system", a major family of bacterial regulatory elements that sense a variety of environmental signals and transduce the information to transcriptionally regulate gene expression.
 Research Interests
Gram-negative bacteria, such as Escherichia coli, have four distinct subcellular locations: the cytoplasm, inner membrane (IM), periplasm, and outer membrane (OM). The noncytoplasmic compartments are collectively termed the cell envelope. We wish to understand cellular assembly, in particular, the process of OM biogenesis. The OM is an asymmetric lipid bilayer containing phospholipids (PLs) in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. Membrane spanning outer membrane proteins (OMPs) typically assume a beta-barrel conformation. All OM components are synthesized in the cytoplasm or the IM and therefore, OM biogenesis requires the transport of these molecules across the cell envelope for assembly at their final cellular location on the other side of the peptidoglycan cell wall. We have used a combination of genetics, biochemistry, and bioinformatics to identify the cellular machinery required for the assembly of OMPs and LPS in the OM and current effort in the lab is directed towards understanding how these machines function in molecular terms, identifying the cellular components required for PL transport to the OM, and how the various envelope stress responses maintain cell integrity.

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