My laboratory is concerned with developing and applying new methods for determining the structure of DNA and DNA-protein complexes. My group introduced the use of the hydroxyl radical as a high-resolution chemical footprinting reagent, and developed the missing nucleoside experiment as a rapid method for revealing the thermodynamically-important contacts made by a protein with its DNA binding site. At present we are using these methods to study DNA flexibility, and structural features of complexes of DNA with RNA polymerase or homeodomains. We are using deuterium kinetic isotope experiments to obtain detailed information on the mechanism of hydroxyl radical cleavage of DNA . We also are developing a new method for performing hydroxyl radical footprinting in vivo.