? This proposal requests support for the 10th Gordon Research Conference (GRC) on 3D Electron Microscopy of Macromolecules. EM occupies a unique position in the biological armamentarium in that it can address questions at the molecular and cellular level that are unapproachable by other structural methods. EM can bridge light microscopic studies at subcellular resolutions with atomic resolution structures provided by X-ray crystallography and NMR. Recent, technical breakthroughs enable 3D structures to be determined with ever-increasing accuracy thereby opening the way to the study of macromolecular systems under defined physiological conditions. The result is new opportunities for understanding biological mechanisms, interactions between macromolecules and the principles of bimolecular design. ? ? This series of conferences fosters an integrated view of biological complexity by bringing together scientists working at different levels of the structural hierarchy. These meetings serve to define the challenges of the future and to focus a concerted approach to problems in the preparation, imaging and interpretation of biological specimens that range in size from the molecular to the subcellular. The impact of the preceding nine conferences has been such that the 3D EM community has come to regard this GRC as an event of pivotal importance. ? ? The 2003 conference is organized around the theme of """"""""Bridging Cellular, Molecular and Atomic Resolution"""""""". Our goal has been to create a dynamic forum for (i) the dissemination of major progress in the field over the past two years and (ii) identification of new technical and biological challenges, which must be addressed in order for 3D EM to become an essential and ubiquitous tool for solving cell biological problems. In the spirit of the GRC, we have chosen a program that represents the frontier of our field. Speakers have been chosen based on the importance of their recent contributions and the potential impact of their particular research approach. Speakers from outside the field have been selected in the hope of fostering interdisciplinary approaches and for challenging the field to reach in directions it has so far not contemplated. Based on past experience, we confidently expect that the 3D EM GRC will continue to play a central role in defining new technical challenges, and in focusing a concerted approach to understanding fundamental biological questions. ? ?
