Richard P. Novick
Recanati Family Professor of Science, Skirball Institute of Biomolecular Medicine, Molecular Pathogenesis. Departments of Microbiology and Medicine
M.D., 1959 NYU School of Medicine
Quorum Sensing, Autoinduction, Regulation, Mobile Genetic Elements, Transduction, Bacteriophages
Skirball Institute of Biomolecular Medicine
540 First Avenue 2nd floor, Lab 1-2
New York, N.Y. 10016
Office Tel: (212) 263-6290
Lab Tel: (212) 263-6294
Fax: (212) 263-5711
Tel: (212) 263-6282
Regulation of virulence and molecular genetics of mobile pathogenicity islands in Staphylococcus aureus
In one of our projects, in collaboration with David Stokes and Tom Muir, we are attempting to determine the crystal structure of the staphylococcal agr signal receptor, AgrC, in order to define the mechanism of signal transduction by this protein. We are also working on the dynamics of agr activation in vitro at the single cell level, using fluorescent gene stags, and propose to move to an in vivo model as soon as the in vitro results are definitive.
In a second project, we are studying the mechanism by which the phage-inducible mobile pathogenicity islands of S. aureus interfere with the propagation of their helper bacteriophages. These mechanisms include an island-encoded protein that inhibits the phage-encoded small terminase subunit, diversion of phage virion proteins to the formation of island-specific capsids, and inhibition of helper phage late gene transcription. The interference also results in increased survival of phage-infected cells by an unknown mechanism. A recent finding is that the mobile islands can participate in genetic transduction, a process formerly thought to be the exclusive province of bacteriophages.
A third area of concentration in our lab is the development of methods to control, treat, or prevent staphylococcal infections. These methods include analysis of agr-encoded quorum-sensing peptides as inhibitors of virulence and for their potential to modify biofilm structure. They also include the development of an antistaphylococcal vaccine and of a powerful staphylolytic enzyme. Finally, we are exploring the potential of probiotics to prevent Clostridium difficile infections owing to antibiotic depletion of the normal intestinal flora.
- Richard P. Novick and Geeta Ram. (2015) The floating (pathogenicity) island: a genomic dessert. Trends Genet (in press)
- Chen J, Ram G, Penadés JR, Brown S, Novick RP. (2015) Pathogenicity island-directed transfer of unlinked chromosomal virulence genes. Mol Cell. 57:138. PMID: 25498143
- Ram G, Chen J, Novick RP.(2014) Precisely modulated pathogenicity island interference with late phage gene transcription. Proc Natl Acad Sci U S A. 111:14536. PMID: 25246539
- Wang B, Zhao A, Novick RP, Muir TW (2014) Activation and inhibition of the receptor histidine kinase AgrC occurs through opposite helical transduction motions. Mol Cell. 53:929. PMID: 24656130
- Geeta Ram, John Chen, Krishan Kumar, Hope F. Ross, Carles Úbeda, Priyadarshan K. Damle, Kristin D. Lane, José R. Penadés, Gail E. Christie, and Richard P. Novick (2012). Staphylococcal pathogenicity island interference with helper phage reproduction is a paradigm of molecular parasitism. Proc Nat Acad Sci, US. Oct 2;109(40):16300-5. PMID: 22991467