Cryoelectron microscopy (cryoEM), three-dimensional (3D) image reconstruction, and atomic modelling play a major role in our proposed studies of the structural analyses of viruses and virus complexes. Viruses are among the best known and studied pathogens. They infect virtually every living organism form bacteria to man and are the subject of intense biochemical, genetic, and structural investigations. Dr. Baker's goal is to answer fundamental questions concerning critical steps in the life cycles of viruses. Along with knowledge gained from biochemical, genetic, immunological, and X-ray crystallographic studies, work aims to provide new insights about: how viruses recognize and attach to target cells; how viruses uncoat or disassemble and deliver the genetic 'payload' to the cell; how the host immune system neutralizes invading viruses; how viruses circumvent the host's immune surveillance; how mature virions assemble from the component protein, nucleic acid, and lipid components; and how viruses are released and initiate a new cycle of infection. Dr. Baker continues to focus structural investigations on studies of viruses and virus complexes and the dynamic events that lie beyond the current realm of crystallographic technology. The extensive number and scope of these studies is made possible through several fruitful collaborations. The analyses often combine information from 3D cryoEM data with available atomic models. The cryoEM methods currently allow 3P structural information to be obtained from vitrified specimens reserved in the 'native' physiological state. This analysis is, however, often limited to the 20-30A resolution level. The laboratory recently acquired a new 200kV transmission electron microscope equipped with a field emission gun and a high resolution, slow- scan, charge-coupled device (CCD) camera. This will greatly improve ability to visualize viruses and virus complexes at resolutions exceeding 20A. In addition, the fitting of atomic models to cryoEM 3P data can reveal 'pseudo-atomic' resolution information about the orientation and binding sites of antibody and receptor molecules on viral capsid surfaces which can be tested and refined by molecular genetics experiments. The structures of several viruses, virus-antibody and virus-receptor complexes will be examined. This will include studies of members of the Picornaviridae, Reovjridae, Microviridae, Togaviridae, and Nodaviridae. All these virus families serve as excellent model systems and have been the subject of extensive biochemical, molecular virology, and molecular biology studies.
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