There is increasing evidence in support of a model of cellular biochemistry in which most proteins exert their biological role through either transient or relatively stable multi-component macromolecular complexes. The key to understanding the function of these complexes lies in their structural investigation by a variety of biophysical methods. The lab studies molecular details of large protein-nucleic acid macromolecules using a variety of new NMR techniques as well as established biophysical approaches. For large complexes, we utilize a rigid body assembly of individually characterized structures using a combination of methods: domain orientation through the measurement of residual dipolar coupling (RDC) by NMR spectroscopy, overall shape determination by small angle neutron or X-ray scattering (SANS/SAXS), and incorporating molecular contact details from such techniques as NMR paramagnetic spin labelling to acquire information on long-range contacts, as well as in vitro mutational analysis and other binding assays. For smaller proteins and domains, standard NMR-based approaches are used, but with additional insight gained from RDC and spin label information. Equally important to the lab is the traditional strength of NMR as a tool to probe the dynamics of biological samples, the characterization of transient interactions, and the possibility to look at structures that exhibit a significant amount of unstructured elements.

Current projects include: