My research interests fall under the general theme of understanding the structural basis for recognition, biochemical function and biological specificity of proteins and nucleic acids. My background in NMR and chemistry frames the way I think, but the deciding factor for choosing problems is not the approach, but rather the biology and biochemistry. Another key characteristic is tight coupling of our research to functional analysis. This strategy is by nature very collaborative and collegial, and has stimulated involvement in several multi-investigator projects.
last updated October 07, 2009
From a technique standpoint, I am in the midst of evolving towards a broad-based vision of structural biology/molecular biophysics that involves the complementary application of different structural approaches including spectroscopy, scattering, crystallography and microscopy. I am interested in exploring how different structural approaches can be combined. NMR remains the core approach, but is used mostly as a tool for characterization of structural interfaces and dynamics. X-ray crystallography is the method of choice when structure determination is needed. Other structural, biophysical and biochemical methods as well as computational approaches are also tightly integrated into our research.
The evolution in approach came in concert with the general shift in the field of structural biology to increasingly complex systems. A significant part of our research is now devoted to multi-protein complexes, with programs studying ubiquitination and DNA replication, damage response and repair machinery. These projects build upon the long history of our lab in the study of calcium signal transduction by EF-hand proteins. The essential starting point in most of our current research is 3D structure and characterization of binding interfaces/interactions. This information provides the necessary foundation to achieve the larger goal of elucidating the structural and dynamical mechanisms that enable progression along biochemical pathways.