Biosketch

Thomas J. Silhavy is the Warner-Lambert Parke-Davis Professor of Molecular Biology at Princeton University. Silhavy is a bacterial geneticist 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, and to identify and characterize a two-component regulatory system. He 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, he helped establish gene fusions as an experimental tool. He served as an Instructor of Microbiology at Harvard Medical School for two years, and he worked at the NCI Frederick Cancer Research Facility for five years where he was Director of the Laboratory of Genetics and Recombinant DNA. He came to Princeton in 1984 as a founding member of the Department of Molecular Biology.
Professor 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 served as an Instructor of Microbiology at Harvard Medical School for two years, and he worked at the NCI Frederick Cancer Research Facility for five years where he was Director of the Laboratory of Genetics and Recombinant DNA. He came to Princeton in 1984 as a founding member of the Department of Molecular Biology.
In recognition of his scientific accomplishments, Silhavy was awarded an honorary Doctor of Sciences degree from his alma mater, Ferris State College (1982); was elected Fellow of the American Academy of Microbiology (1994); the American Association for the Advancement of Science (2004); the American Academy of Arts and Sciences (2005); and he is a member of the National Academy of Sciences (2005) and an associate member of EMBO (2008). In 1999, he received an NIH MERIT award; he received the Novitski Prize for creativity from the Genetics Society of America in 2008; and the American Society for Microbiology (ASM) Lifetime Achievement Award in 2016. His commitment to teaching is evidenced by the President’s Award for Distinguished Teaching at Princeton (1993), the Graduate Microbiology Teaching award from ASM (2002), and the Graduate Advising Award at Princeton (2003).

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.

Membership Type

Member

Election Year

2005

Primary Section

Section 44: Microbial Biology

Secondary Section

Section 26: Genetics