Thomas J. Silhavy

Princeton University

Primary Section: 44, Microbial Biology
Secondary Section: 26, Genetics
Membership Type:
Member (elected 2005)


Thomas J. Silhavy is the Warner-Lambert Parke-Davis Professor of Molecular Biology at Princeton University. Silhavy is a bacterial geneticist who has made fundamental contributions to several different fields. He is best known for his work on protein secretion, membrane biogenesis, and signal transduction. Using Escherichia coli as a model system, his lab was the first to isolate signal sequence mutations, to identify a component of cellular protein secretion machinery, and an integral membrane component of the outer membrane assembly machinery. His lab was also the first to identify and characterize a two-component regulatory system.

Silhavy received his BS in Pharmacy (summa cum laude, 1971) from Ferris State College and his MS (1974) and PhD (1975) in Biological Chemistry from Harvard University. As a graduate student with Winfried Boos, he helped characterize the role of periplasmic binding proteins in sugar transport. As a postdoctoral fellow with Jonathan Beckwith at Harvard Medical School he helped establish gene fusions as an experimental tool. He was an Instructor at Harvard Medical School for two years, and he worked at the NCI Frederick Cancer Research Facility for five years before coming to Princeton in 1984 as a founding member of the Department of Molecular Biology.

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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