Visualizing Viruses Inside and Outside the Host Cells

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Date/Time:Monday, 04 Nov 2013 from 4:10 pm to 5:00 pm
Location:Physics 0003
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Wah Chiu (Baylor College of Medicine)

Abstract: Double stranded DNA viruses infecting both prokaryotes and eukaryotes share a common assembly pathway proceeding from a precursor (procapsid) to an infectious virion. In addition to the coat proteins, the procapsid requires scaffolding proteins, absent from the virion, for proper assembly, and a portal for DNA packaging and subsequent DNA ejection. We have used single particle cryo-EM to determine the structures of several phages at near atomic resolutions (Chen et al., PNAS 2011; Baker et al., PNAS 2013). Our symmetry-free reconstructed structure of phages can reveal structures of various protein components that are not organized with an icosahedral symmetry. Using cryo-electron tomography, we have determined the structures of the cyanophage assembly intermediates inside the host cyanobacteria (Dai et al, Nature in press). Such in situ structural studies provide unique opportunity to determine not only the structures of distinct assembly states of the phages in their maturation process but also the effects on the cellular components in the infected host.

Bio: I have been an investigator in the development of experimental and computational methodologies for structural determination of biological assemblies by single particle cryo-electron microscopy (cryo-EM) towards atomic resolution in last two decades. We have recently succeeded in determining maps and associated models of several chaperonins and viruses at ~4 resolution using single particle cryo-EM without using crystallography. In the past few years, i have expanded our technology development to cryo-electron tomography of organelles, cells and protein aggregates. I direct two NIH Centers. One of them is the NIGMS P41 Biotechnology Resource Center (P41GM103832) to support cryo-EM methodology developments driven by over 30 biological projects with investigtors from US and abroad. The other Center is the Protein Folding Machinery Center (PN2EY016525) aimed at translating basic science to chaperone-based therapeutics for neurodegnerative diseases and cancer with 12 collaborative investigators from 7 academic institutions across the country. I have also invloved directly with several training and outreach activities in Houston and around the world to promote the usage of cryo-EM/ET for structural research. As the director of our Structural and Computational Biology and Molecular Biophysics Ph.D. Program at Baylor, I have coordinated the course in computational mathematics for biomedical sciences and systems biology. As the founding co-director of the Keck Center for Computational Biology, I have involved in overseeing several training grants in quantitative biomedicine currently supporting over 60 pre and post-doctoral trainees in six academic institutions in the Houston and Galveston Area.