Research in my laboratory is focused on understanding the molecular mechanisms and cellular functions of multisubunit assemblies that control the organization, preservation, and flow of genetic information. We are particularly interested in developing atomic-level models that explain how chemical energy is transduced into force and motion, and how dynamic assemblies control DNA replication, gene expression, chromosome superstructure, and other essential nucleic-acid transactions.

My group’s approach relies on a blend of structural, biochemical, and biophysical methods to define the architecture, function, evolution, and regulation of biological complexes. X-ray crystallography and traditional biochemistry have traditionally formed the core of our approach; however, we are increasingly merging these methods with other experimental tools such as small-angle X-ray scattering, single-molecule studies, and electron microscopy. Since the inception of the group in 1995, we have biochemically and structurally defined the range and nature of key functional intermediates and transitions for a variety of nucleotide-dependent ‘molecular machines,’ including topoisomerases, helicases, condensins, and replication initiation complexes.

Our efforts have allowed us to define how biological systems use these factors to organize, transport, and reshape target nucleic-acid substrates at a physical level, and how their actions are controlled by both protein-protein interactions and small-molecule agents. My lab has a consistent track record of bringing new concepts and fundamentally important discoveries to the field, and in innovating new approaches and technologies to studying multi-protein and protein/nucleic-acid assemblies in general. Training has been a similarly important facet of my efforts; to date, 22 doctoral students and 20 post-doctoral fellows have worked in my group. All who have left thus far have gone on to productive careers in academia (18), biotechnology/pharma (10), law (2), medicine (1), and consulting (1).