Division of Biological Sciences

Tim Baker

Tim Baker

Professor
Section of Molecular Biology, UCSD
Department of Chemistry and Biochemistry

e-mail: tsb@ucsd.edu
Lab Homepage: Baker Lab

   The primary thrust of our research is to image viruses and gain insights about how they interact with their hosts, replicate, and mature. We use the tools of cryo-electron microscopy (CryoEM) and three-dimensional (3D), image-reconstruction to observe viruses or virus-like particles and examine intermolecular interactions at sub-nanometer resolutions. At such resolution, it is possible to discern and distinguish viral components (protein, nucleic acid, lipid, carbohydrate) and even visualize secondary structural details such as alpha-helices and beta-sheets in proteins. Viruses currently under investigation include bacteriophages phi-29 and P22; gemini viruses, several partitiviruses, parvoviruses (human bocavirus and several serotypes of adeno-associated viruses both as native virions and complexed with neutralizing antibodies and receptor molecules), reoviruses, a tetravirus, two distinct totiviruses, and several, large dsDNA viruses that infect algae and insects; and a family of small, enveloped, ssRNA viruses that include members that are serious human pathogens and have been listed as possible agents of bio-terrorism.

    Samples for CryoEM are flash frozen so quickly that they are preserved in a thin layer of non-crystalline ice. They are maintained in this state in the transmission electron microscope, which is cooled to either liquid nitrogen or liquid helium temperatures. Two state-of-the-art, computer-controlled microscopes are available for this work. They greatly assist the researcher in collecting the tens of thousands of virus images that are often required to obtain high-resolution 3D reconstructions.

    Computer reconstruction techniques are continuously being developed to more effectively and efficiently extract usable information from the noisy image data. With help from San Diego Supercomputer Center staff, we have developed a new system (AUTO3DEM) that automates much of the tedious steps in the 3D reconstruction process. We often are now able to obtain reconstructions at sub-nanometer resolution in a few days or less after the images are recorded.

 Baker Figure 3  Baker Figure 1  Baker Figure 2


Tang, J., G. C. Lander, A. Olia, R. Li, S. Casjens, P. Prevelige Jr., G. Cingolani, T. S. Baker, and J. E. Johnson (2011) Peering down the barrel of a bacteriophage portal: the genome packaging and release valve in P22. Structure, 19:496-502.

Gurda, B. L., K. N. Parent, H. Bladek, R. S. Sinkovits, M. A. Dimattia, C. Rence, A. Castro, R. McKenna, N. Olson, K. Brown, T. S. Baker, and M. Agbandje-McKenna (2010) Human Bocavirus capsid structure: insights into the structural repertoire of the Parvoviridae.  J. Virol. 84:5880-5889

Ng, R., L. Govindasamy, B.L. Gurda, R. McKenna, O.G. Kozyreva, R.J. Samulski, K.N. Parent, T.S. Baker, and M. Agbandje-McKenna (2010) Structural characterization of the dual glycan binding adeno-associated virus serotype 6. J. Virol. 84:12945-12957

Parent, K. N., R. Khayat, M. M. Suhanovsky, L. Tu, J. Cortines, C. M. Teschke, J. E. Johnson, and T. S. Baker (2010). P22 coat protein structures reveal a novel mechanism for capsid maturation: stability without auxiliary proteins or chemical crosslinks. Structure 18:390-401.

Parent, K. N., R. S. Sinkovits, M. M. Suhanovsky, C. M. Teschke, E. H. Egelman, and T. S. Baker (2010) Cryo-reconstructions of P22 polyheads suggest that phage assembly is nucleated by trimeric interactions among coat proteins.  Phys. Biol., 7:045004.

Sinkovits, R. S. and T. S. Baker (2010) A tale of two symmetrons: rules for construction of icosahedral capsids from trisymmetrons and pentasymmetrons. J. Struct. Biol. 170:109-116

Suhanovsky, M. M., Parent, K. N., Dunn, S. E., Baker, T. S., and Teschke, C. M. (2010) Determinants of bacteriophage P22 polyhead formation: the role of coat protein flexibility in conformational switching.  Molec. Microbiol. 77:1568-1582.

Tang, J., W. F. Ochoa, H. Li, W. M. Havens, M. L. Nibert, S. A. Ghabrial, and T. S. Baker (2010) Structure of Fusarium poae virus 1 shows conserved and variable elements of partitivirus capsids and evolutionary links to picobirnavirus.  J. Struct. Biol. 172:363-371.

   Tim Baker received his Ph.D. from UCLA and was a Jane Coffin Childs postdoctoral fellow at Cambridge University, a NIH Postdoctoral Fellow and the Charles A. King Trust Postdoctoral Fellow at Brandeis University. From 1983-2004, he was on the Faculty of Purdue University where he earned the Herbert Newby McCoy Award for Scientific Achievement and a NIH NIGMS MERIT award. He received a joint faculty appointment in Biological Sciences and Chemistry & Biochemistry at UCSD in 2004.