VOLLUM INSTITUTE
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Eric Barklis received a B.A. degree in Biology from the Massachusetts Institute of Technology in 1973. He began graduate study in English Literature at Northeastern University, then returned to MIT for a Ph.D. in Biochemistry. After three years of postdoctoral study at the Whitehead Institute, Barklis received joint faculty appointments in the Vollum Institute and the Department of Microbiology in 1987. He was promoted to associate professor in 1994, became director of the OHSU Electron Microscopy core in 1999, and was promoted to professor in 2001. Research InterestsResearch in the Barklis lab focuses on the assembly of macromolecular structures using molecular genetic, biochemical, and biophysical techniques. The lab addresses how the building blocks of enveloped viruses assemble to form virus particles, with an emphasis on retroviruses and hantaviruses. To analyze virus particles and macromolecular complexes, the lab expresses and purifies individual viral proteins and nucleic acids and then assembles them in vitro to form two dimensional crystals or large helices. Typically, virus assemblies are examined by transmission electron microscopy (EM). Low-dose images are digitized to generate 5-25Å resolution reconstructions using computer-based image alignment and averaging or electron diffraction approaches. Alternatively, for two dimensional arrays of lipid bilayer-bound proteins, atomic force microscopy (AFM) has been employed. For this technique, membrane-bound proteins are adhered to mica or graphite substrates and are scanned with a silicon nitride probe tip to measure height differences at nanometer resolutions. Predictions from in vitro EM and AFM investigations are tested on virus particles and purified proteins using cell culture, nucleic acid binding, protein binding, mutagenesis, and microscopic techniques. The methods developed by the Barklis lab can be adapted to the analysis of subcellular complexes, interactions between proteins and nucleic acids, and to the elucidation of membrane receptor and channel protein structures. The lab is also using the knowledge gained from these experiments in long-term studies aimed at designing molecular machines and surfaces for nanotechnology applications. An immediate, practical goal is to identify structure-based compounds that can be employed as safe and specific antiviral agents. Selected PublicationsScholz, I., Arvidson, B., Huseby, D., and Barklis, E. (2005) Virus particle core defects caused by mutations in the human immunodeficiency virus capsid N-terminal domain. J. Virology 79:1470-1479. Mayo, K., Huseby, D., McDermott, J., Arvidson, B., Finlay, L., and Barklis, E. (2003) Retrovirus capsid protein assembly arrangements. J. Mol. Biol. 325:225-237. Arvidson, B., Seeds, J., Webb, M., Finlay, L., and Barklis, E. (2003) Disruption of the retrovirus capsid interdomain linker region. Virology 308:166-177. Alfadhli, A., Steel, E., Finlay, L., Bachinger, H.P., and Barklis, E. (2002) Hantavirus nucleocapsid protein coiled-coil domains. J. Biol. Chem. 277:27103-27108. Mayo, K., McDermott, J., and Barklis, E. (2002) Hexagonal organization of Moloney murine leukemia virus capsid protein. Virology 298:30-38. Mayo, K., Vana, M., McDermott, J., Huseby, D., Leis, J., and Barklis, E. (2002) Analysis of Rous sarcoma virus capsid protein variants assembled on lipid monolayers. J. Mol. Biol. 316:667-678. Alfadhli, A., Love, Z., Arvidson, B., Seeds, J., Willey, J., and Barklis, E. (2001) Hantavirus nucleocapsid protein oligomerization. J. Virology 75:2019-2023.
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