Viral infection significantly impacts all forms of life. Since every virus and bacteriophage requires correct organization of its capsid proteins (CPs), the mechanisms by which these CPs assemble must ultimately be determined in order to devise efficacious methods to circumvent infection or its spread. Bacteriophage P22 shares features of assembly and a high degree of structural conservation among the major CPs of numerous dsDNA viruses, including the human herpesviruses, and will serve as a model system in the proposed research. We will study the stages of infection in P22-infected Salmonella, employing both electron tomography of samples treated by High Pressure Freezing and Freeze Substitution (HPF/FS) and fluorescence microscopy. Initially, our focus will be on visualizing early events of infection, including P22 attachment to cells and subsequent release of the minor proteins gp16, gp7, and gp20 into cells. Ultimately, these methods will help us characterize many stages of the virus life cycle, including those that occur during the end of the cycle such as procapsid assembly and maturation. In addition, we propose to employ electron cryo-microscopy on single particles to determine the structural transitions that occur in the major capsid protein as the virion matures. Adding and mastering these powerful techniques to my repertoire will bolster my path towards a faculty position at a top tier institution.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI078624-01A2
Application #
7745768
Study Section
Special Emphasis Panel (ZRG1-F13-C (20))
Program Officer
Park, Eun-Chung
Project Start
2009-08-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
1
Fiscal Year
2009
Total Cost
$47,210
Indirect Cost
Name
University of California San Diego
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Parent, Kristin N; Tang, Jinghua; Cardone, Giovanni et al. (2014) Three-dimensional reconstructions of the bacteriophage CUS-3 virion reveal a conserved coat protein I-domain but a distinct tailspike receptor-binding domain. Virology 464-465:55-66
Parent, Kristin N; Deedas, Christina T; Egelman, Edward H et al. (2012) Stepwise molecular display utilizing icosahedral and helical complexes of phage coat and decoration proteins in the development of robust nanoscale display vehicles. Biomaterials 33:5628-37
Brodin, Jeffrey D; Ambroggio, X I; Tang, Chunyan et al. (2012) Metal-directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays. Nat Chem 4:375-82
Yan, Xiaodong; Parent, Kristin N; Goodman, Russell P et al. (2011) Virion structure of baboon reovirus, a fusogenic orthoreovirus that lacks an adhesion fiber. J Virol 85:7483-95