virus picture

HPMI

HIGH PERFORMANCE MOLECULAR IMAGING




People and Projects

Hong Zhou Viral Reconstructions of Herpes.

My research interest focuses on developing high performance image processing software for the 3D structural determination of viruses from electron cryomicroscopy (cryoEM) images. Structural determination from cryoEM images consists three major steps: particle orientation and center determination, orientation and center refinement, and 3D reconstruction. My current project is to develop novel algorithms for the orientation and center refinement of high resolution (but noisy) cryoEM images.

Amy McGough Helical Reconstructions of Actin.

My research involves structural studies of a protein called gelsolin which binds to and breaks actin filaments as part of its normal function in living cells. This ability to sever filaments makes gelsolin a key player in cellular processes such as motility and differentiation, both of which rely on dramatic reorganizations of the actin cytoskeleton. In addition, gelsolin holds promise as a therapeutic agent for cystic fibrosis by acting as a mucolytic agent for CF sputum.

Karen Haskell

Ridgway Scott Algorithms for enhanced resolution.

In collaboration with Professor Wah Chiu of the Baylor College of Medicine, we are attempting to develop new algorithms for improved imaging of electron micro-graphs. Electron microscopy is an exciting technique for the discovery of the biological structure of large proteins. Current methods limit the reconstruction to a resolution several times greater than the physical resolution of the electron microscope. We hope both to improve the resolution and to speed the process of data reduction. Ultimately, we hope to change the character of structural imaging so that large numbers of high-resolution structures can be determined in the amount of time now required for a single low-resolution image. Since knowledge of the basic structure of macromolecular assemblies, such as viruses and cytoskeletal components, leads to a deeper understanding of their function, this will open the door to a host of new biomedical advances.



Publications

Lamture, J.B., Zhou, Z.H., Kumar, A.S., Wensel, T.G. (1995) Luminescence properties of Terbium (III) complexes with 4-substituted dipicolinic acid analogues, Inorganic Chem., 34, No. 4. 864-869.

Lu, G.Y., Zhou, Z.H., Jakana, J., Cai, D.Y., Chen, S.X., Wei, X.C., Gu, X.C., and Chiu, W. (1995) Three-dimensional Structure of Rice Dwarf Virus by Electron Cryomicroscopy, High Tech. Let. 5, No 1,1-4.

McGough, A. and M. Way. 1995. Molecular model of an actin filament capped by a severing protein. J. Struct. Biol. 115:144-150.

McGough, A., M. Way, and D. DeRosier. 1994. Determination of the alpha-actinin binding site on actin filaments by cryoelectron microscopy and image analysis. J. Cell Biol. 126:433-443.

McGough, A. and R. Josephs. 1990. On the structure of erythrocyte spectrin in partially expanded membrane skeletons. Proc. Natl. Acad. Sci. 87:5208-5212.

Zhou, Z.H., Hardt, S., Wang, B., Sherman, M.B., Joanita, J., Chiu, W. (1996) CTF determination of images of ice-embedded single particles using a graphics interface, J. Struct. Biol. Vol. 115 in the press.

Zhou, Z.H., He, J., Jakana, J., Tatman, J.D., Rixon, F., Chiu, W. (1995) Assembly of VP26 in herpes simplex virus-1 inferred from structures of wild-type and recombinant capsids, Nature Struct. Biol. Vol. 2, No. 11. 1026-1030.

Zou, Z.H., Prasad, B.V.V., Jakana, J., Rixon, F., Chiu, W. (1994) Protein subunit structures in the herpes simplex virus A-capsid determined from 400 kV spot-scan electron cryomicroscopy, J. Mol. Biol., 242:456-469.

Zhou, Z.H., Chiu, W. (1993) Prospects for using an IVEM with a FEG for imaging macromolecules towards atomic resolution, Ultramicroscopy 49: 407-416.



Abstracts and Proceedings

Chiu, W., Jakana, J., Zhou, Z.H., Thuman-Commike, P. (1995) 400 keV electron cryomicroscopy and computer reconstruction of spherical viruses, June 4-7, Ottawa, Canada.

DeRosier, D., A. McGough, L. A. Melanson, D. Morgan, and C. Owen. 1994. High resolution studies of helical structures by electron cryomicroscopy. Proceedings of the 13th International Congress on Electron Microscopy. Paris, FRANCE.

Lu, G.Y., Zhou, Z.H., Jakana, J., Cai, D.Y., Chen, S.X., Gu, X.C., Chiu, W. (1994) Three-dimensional structure of rice dwarf virus determined by electron cryomicroscopy. The Third Asia-Pacific congress of medical virology, p.p. 252, Oct. 23-28, Beijing, China.

McGough, A. and R. Josephs. 1992. Electron microscopy and image reconstruction reveal the structural basis for spectrin's elastic properties. Proceedings of the Electron Microscopy Society of America. Boston, Massachusetts.

McGough, A and R. Josephs. 1990. The helical structure of erythrocyte spectrin: Implications for red cell elasticity. J. Cell. Biochem. Suppl. 14a: 240.

McGough, A. and R. Josephs. 1989. The structure of partially expanded erythrocyte spectrin. Proceedings of the Electron Microscopy Society of America. San Antonio, Texas.

McGough, A., B. Carragher, and R. Josephs. 1989. Image analysis reveals periodic structure in negatively stained spectrin. Biophys. J. 55: 216a.

Zhou, Z.H., He, J., Jakana, J., Tatman, J.D., Rixon, F.J., Chiu, W. (1995) Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3D structure of recombinant capsid, Proc. 53rd Annu. Meeting of the Micros. Soc. of America. Aug. 13-17, Kansas City, MO.

Zhou, Z.H., He, J., Jakana, J., Tatman, J.D., Rixon, F.J., Chiu, W. (1995) Defining interaction and assembly of VP26 in herpes capsid from 3d structure of recombinant capsids,20th International Herpesvirus Workshop, July 29 - Aug. 3, Groninger, The Netherlands.

Zhou, Z.H., He, J., Jakana, J., Tatman, J.D., Rixon, F.J., Chiu, W. (1995) Domain structures of VP26 and VP5 determined by electron cryomicroscopy of recombinant and naturally occurring HSV-1 capsids, The 14th annual meeting of American Society for Virology, p.p. 200, July 8-12, Austin, TX.

Zhou, Z.H., He, J., Jakana, J., Tatman, J.D., Rixon, F.J., Chiu, W. (1995) Assembly of herpesvirus capsids inferred from the 3D structures by 400keV spot-scan electron cryomicroscopy, Gordon Research Conference - Three Dimensional Electron Microscopy of Macromolecules, June 25-30, New Hampton School, NH

Zhou, Z.H., Jakana, J., Prasad, B.V.V., Rixon, F.J., Chiu, W. (1995) Structural variations between herpes simplex virus capsids at different maturation stpes observed by electron cryomicroscopy,West Coast Crystallography Workshop, March 12-15, Montarey, CA.

Zhou, Z.H., Prasad, B.V.V., Jakana, J., Rixon, F.J., Chiu, W. (1994) Protein subunit structure of herpes simplex virus A-capsid determined from 400-kV electron cryomicroscopy. The Third Asia-Pacific congress of medical virology, p.p. 239, Oct. 23-28, Beijing, China.

Zhou, Z.H., Prasad, B.V.V., Jakana, J., Rixon, F.J., Chiu, W. (1994) Protein subunit structure of herpes simplex virus A-capsid determined from 400-kV electron cryomicroscopy. The 19th international herpesvirus workshop, July 30 - Aug. 5, Vancouver, Canada.

Zhou, Z.H., Prasad, B.V.V., Jakana, J., Rixon, F.J., Chiu, W. (1994) Protein subunit structures in capsomeres of herpes simplex virus capsid determined by 400kV spot-scan electron cryomicroscopy. The 13th annual meeting of American Society for Virology, p.p. 108, July 9-13, Madison, WI.

Zhou, Z.H., Jakana, J., Prasad, B.V. V., Rixon, F.J., Chiu, W. (1994) Subunit structures in capsomeres of herpes simplex virus capsid revealed by 400kV spot-scan electron cryomicroscopy, Biophysical J., Vol. 66 No. 2, pt. 2, A135. 38th Annual Meeting of the Biophysical Society, New Orleans, LA.



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