M.S., 1989, Moscow Instiute of Physics and Technology, Dolgoprudny, Russia
Ph.D., 1992, Moscow Instiute of Physics and Technology, Dolgoprudny, Russia
Postdoc, 1993-2000, University of California, Berkeley
chromatin structure and dynamics, single DNA nanomanipulations, antibiotic discovery, computational and mathematical biophysics
Chromatin Structure and Dynamics
Chromosome structure defines its function and, thereby, the physiological state of the entire cell. Errors in chromosome packing are detrimental for the cell and lead to many devastating human diseases. We investigate global chromosome organization as well as molecular motors that organize both bacterial and eukaryotic chromosomes. Our main focus has been on bacterial and eukaryotic condensins, which are responsible for global folding of the chromosome in organisms ranging from bacteria to humans. By blending methods from DNA topology, biochemistry, cell biology, genetics and single DNA nanomanipulations, we discovered that the Escherichia coli condensin MukBEF acts as a network of ATP-modulated macromolecular clamps that brings distant DNA segments together. This novel enzymatic activity befits the protein that acts at the heart of the chromosome and offers new insights into chromosome biogenesis. We are now working on harnessing the activity of condensins in order to gain control of the chromosome and alleviate human disease. Current projects involve (i) mechanistic biochemistry of bacterial and yeast condensins, (ii) anti-condensin drug discovery and development, where our current lead compounds display an impressive activity against a broad range of multidrug resistant Gram-positive and Gram-negative pathogens, and (iii) chromosome biology of Pseudomonas aeruginosa, where condensins from SMC and MksBEF superfamilies play an exceptionally elegant game in orchestrating chromosome dynamics and are even involved in epigenetic regulation.
In another line of investigation, we work with the Center for Antibiotic Discovery and Resistance on deducing chemical rules of compound permeation into bacteria. We constructed a mathematical model of drug accumulation and activity in bacteria and presently apply it for optimization of bioactive compounds for permeation into bacteria