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Integrative Structural and Computational Biology

Erica Saphire, PhD

Professor Adjunct
Department of Immunology and Microbiology
California Campus
Laboratory Website
(858) 784-8602

Scripps Research Joint Appointments

Professor, Department of Immunology and Microbial Science
Professor, Department of Integrative Structural and Computational Biology

Research Focus

Structural Studies of Viral Hemorrhagic Fever Pathogenesis

We study viruses with compact genomes of only 4-7 genes. Consequently, each protein is critical, many are obligated to perform multiple functions, and some actually rearrange their structures to achieve those new functions. As a result, these few polypeptides accomplish a surprisingly complex set of biological functions: immune evasion, receptor recognition, cell entry, transcription, translation, assembly and exit.

Viruses with limited genomes also offer a well-defined landscape of possible protein-protein interactions, which together comprise the totality of their life cycle. By systematically analyzing the structures and functions of each protein the virus encodes (as we set out to do for the Ebola and Lassa viruses in particular), we gain fundamental insights into the biology of entry, immune evasion, and assembly, and can decipher the collaborative roles of these proteins in pathogenesis.


Ph.D., Macromolecular and Cellular Structure and Chemistry, The Scripps Research Institute, 2000

Awards & Professional Activities

Presidential Early Career Award in Science and Engineering
Investigators in the Pathogenesis of Infectious Disease, Burroughs Wellcome Fund
ICAAC Young Investigator Award, American Society for Microbiology
New Initiatives in Global Infectious Disease, Ellison Medical Foundation
Career Award in the Biomedical Sciences, Burroughs Wellcome Fund
Surhain Sidhu Award for outstanding contributions  to the field of diffraction

Selected References

Bornholdt, Z. A., T. Noda, D. M. Abelson, P. Halfmann, M. R. Wood, Y. Kawaoka, and E. O. Saphire. 2013. Structural Rearrangement of Ebola Virus VP40 Begets Multiple Functions in the Virus Life Cycle. Cell 154:763-774. PMC3753998

Bale, S., J. P. Julien, Z. A. Bornholdt, C. R. Kimberlin, P. Halfmann, M. A. Zandonatti, J. Kunert, G. J. Kroon, Y. Kawaoka, I. J. MacRae, I. A. Wilson, and E. O. Saphire. 2012. Marburg virus VP35 can both fully coat the backbone and cap the ends of dsRNA for interferon antagonism. PLoS Pathog 8:e1002916. PMC3441732

Hastie, K. M., L. B. King, M. A. Zandonatti, and E. O. Saphire. 2012. Structural Basis for the dsRNA Specificity of the Lassa Virus NP Exonuclease. PLoS One 7:e44211. PMC3429428

Zhang, A. P., Z. A. Bornholdt, T. Liu, D. M. Abelson, D. E. Lee, S. Li, V. L. Woods, Jr., and E. O. Saphire. 2012. The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold. PLoS Pathog 8:e1002550. PMC3285596

Olal, D., A. I. Kuehne, S. Bale, P. Halfmann, T. Hashiguchi, M. L. Fusco, J. E. Lee, L. B. King, Y. Kawaoka, J. M. Dye, Jr., and E. O. Saphire. 2012. Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus. J Virol 86:2809-2816. PMC3302272

Hastie, K. M., T. Liu, S. Li, L. B. King, N. Ngo, M. A. Zandonatti, V. L. Woods, Jr., J. C. de la Torre, and E. O. Saphire. 2011. Crystal structure of the Lassa virus nucleoprotein-RNA complex reveals a gating mechanism for RNA binding. Proc Natl Acad Sci U S A 108:19365-19370. PMC3228486

Bale, S., T. Liu, S. Li, Y. Wang, D. Abelson, M. Fusco, V. L. Woods, Jr., and E. O. Saphire. 2011. Ebola virus glycoprotein needs an additional trigger, beyond proteolytic priming for membrane fusion. PLoS Negl Trop Dis 5:e1395. PMC3216919

Dias, J. M., A. I. Kuehne, D. M. Abelson, S. Bale, A. C. Wong, P. Halfmann, M. A. Muhammad, M. L. Fusco, S. E. Zak, E. Kang, Y. Kawaoka, K. Chandran, J. M. Dye, and E. O. Saphire. 2011. A shared structural solution for neutralizing ebolaviruses. Nat Struct Mol Biol 18:1424-1427. PMC3230659

Hastie, K. M., C. R. Kimberlin, M. A. Zandonatti, I. J. Macrae, and E. O. Saphire. 2011. Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression. Proc Natl Acad Sci U S A. PMC3038715

Kimberlin, C. R., Z. A. Bornholdt, S. Li, V. L. Woods, Jr., I. J. MacRae, and E. O. Saphire. 2010. Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression. Proc Natl Acad Sci U S A 107:314-319. PMC2806767

Lee, J. E., M. L. Fusco, A. J. Hessell, W. B. Oswald, D. R. Burton, and E. O. Saphire. 2008. Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature 454:177-182. PMC2700032