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The structural basis of ebola viral pathogenesis

Wednesday, November 6, 2013


Erica Ollmann Saphire, Ph.D.
Professor, Department of Immunology and Microbial Science
The Scripps Research Institute

Erica Ollmann Saphire studies the molecular basis of viral pathogenesis focusing on filoviruses, arenaviruses, and the immune response against them. Her work has identified structures of viral surface glycoproteins, mapped the binding sites of key neutralizing antibodies, provided the only available structure of the intact human Immunoglobulin G (IgG), revealed molecular mechanisms of innate immunosuppression by different virus families, and illustrated genome binding and matrix assembly. Most recently, her lab has demonstrated that certain proteins, like the Ebola virus matrix, arrange into different structures in order to extend the functional complexity of their compact genomes. Dr. Saphire has received many awards recognizing her work including the Presidential Early Career Award in Science and Engineering and the Investigators in the Pathogenesis of Infectious Disease and Career Awards in the Biomedical Sciences from the Burroughs Wellcome Fund. In addition to her work in structural biology, she directs the Viral Hemorrhagic Fevers Immunotherapeutics Consortium and is on the Scientific Leadership Board of the Global Virus Network.


Dr. Saphire’s lab studies viruses with compact genomes that encode just four to seven genes each. Viruses with limited genomes offer a defined landscape of possible protein-protein interactions. Each protein is critical—many are obligated to perform multiple functions and some rearrange their structures to achieve those new functions. As a result, these few polypeptides accomplish a surprisingly complex set of biological functions including immune evasion, receptor recognition, cell entry, transcription, translation, assembly and exit. Dr. Saphire systematically analyzes the structures and functions of each protein encodes by the virus to gain fundamental insights into the biology of entry, immune evasion, and assembly, and to decipher the collaborative roles of these proteins in pathogenesis. In this lecture, Dr. Saphire will illustrate the molecular function throughout the viral life cycle: how the Ebola virus glycoprotein remodels itself during viral entry and how this remodeling affects the antibody response; how the Ebola and Lassa viruses suppress host innate immune signaling; and how the Ebola matrix protein assembles into one structure to bud new virions and into a different conformation to bind RNA and control transcription inside infected cells.

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