David A. Agard

As a structural biologist, we are fundamentally interested in understanding the complex relationships between structure and function at both the molecular and cellular level. These interests have driven research programs aimed at understanding the mechanisms of assisted protein folding (pro regions and molecular chaperones), the mechanism of microtubule assembly, the structural basis for ligand specificity (alpha-lytic protease, estrogen receptors) and the architecture and function of cellular machines (centrosomes and chromosomes). In brief, our studies on alpha-lytic protease folding revealed that the native state need not be at a global free energy minimum. Our work on microtubule assembly has redefine the role of GTP and revealed that the lattice and not the nucleotide acts as the allosteric effector. Moreover, microtubule assembly proceeds via a 2D crystallization mechanism and not via a classic nucleation-polymerization model. Our studies of the Hsp90 molecular chaperone are uncovering the conformational dynamics of its ATPase cycle and providing new insights into its mechanism of client protein remodeling. With John Sedat, we have developed new widefield light microscopies that obtain resolutions well beyond the diffraction limit and have pioneered new approaches for automated EM tomography.