B.A., Biochemistry Brandeis University, 1986
Ph.D., Molecular Biophysics and Biochemistry Yale University, 1992
Post-doctoral fellow at LMB/NIDDK/NIH 1993-1997
How do jumping genes jump and how do recombinases orchestrate DNA rearrangements? We combine biochemistry, structural biology, and microbiology to get mechanistic, molecular-level answers. Some of our current projects are briefly described below - please write me for more detail!
The SCCmec element of MRSA:
This rather mysterious mobile genetic element carries the methicillin resistance gene that renders S. aureus resistant to a broad range of penicillins. We are working to understand the molecular details of its lifestyle: what are the functions of the conserved proteins it encodes, how do its recombinases excise and insert it, and what happens between its excision from one host’s chromosome and appearance in a new host strain.
Serine recombinases: bizarre protein swivels :
These are a family of site-specific DNA recombinases that cut and paste DNA at defined sequences, and are useful genetic tools. Our favorites from this family are the recombinases encoded by SCCmec and Sin, which aids stable maintenance of multi-resistance plasmids in S. aureus. These recombinases form a very unusual protein swivel in which half of an entire DNA-linked tetramer rotates 180 relative to the other half. How do they do it? What does the full rotation pathway look like in 3D? What controls them?
These catalyze the mobility of numerous DNA transposons, contributing to horizontal gene transfer and antibiotic resistance in bacteria. Our combined structural and functional work asks how these enzymes efficiently move genes around and how exploit DNA bendability and product binding energy to cheat thermodynamics by driving forward a reaction that should be chemically reversible.