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 from bacteria, yeast and humans in order to gain control of the chromosome.
Our current research proceeds in three directions. First, we continue mechanistic exploration of condensins with the focus on their activity within its native substrate, the chromosome. Second, we develop single DNA nanomanipulation and microfluidics methods for studies of multi-component macromolecular assemblies with complex architectures. Third, we are engaged in drug discovery studies aimed at development of new antimicrobials against currently intractable and emerging pathogens.