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Virus structure, Structural Informatics, and Vaccine Design

Our laboratory interests include: 

  • Three dimensional structural analyses of viral capsids and proteins
  • Structural Bioinformatics and Homology Modeling
  • Customized Vaccine Design

We employ methods in:

  • Structural biology: X-ray crystallography, cryo-electron microscopy (cryo-EM)
  • Bioinformatics: relational databases and data-mining
  • Molecular Biology: vaccine/protein design, expression
  • Biophysical methods

Research Focus

Our research interests are to determine the three dimensional structures of proteins and molecular assemblies such as viruses and to identify the structural underpinnings and requirements for the self-assembly, stability and targeting specificities of viral capsids (Venkataraman et al., 2008; Reddy et al., 2010). We further use this information as a knowledge base to design novel protein shells that polyvalently display multiple copies of peptides/proteins of interest. We employ X-ray crystallography, cryo-EM, computational, bioinformatics and genetic methods to investigate these areas of research.

Viruses are highly evolved macromolecular assemblages that perform a variety of functions during their life cycle: self-assemble to form closed capsids, selective packaging of the genome, binding and followed by delivery of the genetic material to the susceptible target cells. Simple viruses such as non-enveloped viruses form capsids that are homogeneous in their composition and quaternary architecture. Hence are amenable for structural and functional analyses. 

In collaboration with Professor Glen Nemerow's group at TSRI, we recently determined the crystal structure of Human adenovirus at 3.5Å resolution (Reddy et al, 2010), the biggest virus structure yet determined to date. 

We are also actively involved in maintaining and developing the popular virus structure database, VIPERdb (http://viperdb.scripps.edu) of spherical virus structures and their computational and bio-informatics analysis (Carrillo-Tripp et al, 2009).

We use simple virus capsids as platforms for displaying pathogenic epitopes to generate customized vaccines (Kumar et al., 2009).

Significant publications:

Yu, X., Veesler, D., Campbell, M., Barry, M.E., Asturias, F., Barry, M.A. and Reddy, V.S. Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses. Sci. Adv. 3, e1602670 (2017)

Reddy, V.S. Application of the phase extension method in virus crystallography. Crystallogr Rev 22, 128-140 (2016).

Reddy VS, Natchiar SK, Stewart PL, Nemerow GR. Crystal structure of human adenovirus at 3.5 A resolution. Science 2010; 329(5995): 1071-1075. 

Carrillo-Tripp M, Shepherd CM, Borelli IA, Venkataraman S, Lander G, Natarajan P, Johnson JE, Brooks CL, 3rd, Reddy VS. VIPERdb2: an enhanced and web API enabled relational database for structural virology. Nucleic Acids Res 2009;37(Database issue):D436-442.

Kumar, S., Ochoa, W., Singh, P., Hsu, C., Schneemann, A., Manchester, M., Olson, M., and Reddy, V. (2009). Tomato bushy stunt virus (TBSV), a versatile platform for polyvalent display of antigenic epitopes and vaccine design. Virology 388(1), 185-90.

Venkataraman, S., Reddy, S. P., Loo, J., Idamakanti, N., Hallenbeck, P. L., and Reddy, V. S. (2008). Structure of Seneca Valley Virus-001: an oncolytic picornavirus representing a new genus. Structure 16(10), 1555-61. PMC2572565

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