The High-Throughput Functional Genomics, Proteomics, and Computational Core (referred to as """"""""Core B"""""""") of this program project proposal has four distinct research support goals that are designed to enable the Individual objectives as described In each project. These research roles are as follows. First, Core B will provide high-throughput mass spectrometry services for the purpose of establishing viral and host protein-protein Interaction maps. Second, Core B will provide advanced computational research support, by bringing modern bioinformatic approaches to protein sequence, structure, and function analysis to bear on the expected deluge of functional data this proposal will generate. Third, Core B will provide leading-edge ultra deep sequencing support to the program project. A major focus of the proposal is the analysis of viral diversity, population structure and plasticity, especially with respect to the evolution of quasi-specles. Ultra deep sequencing (such as that provided by lllumina Solexa technology) allows quantitative and precise measurements of genome-wide genetic dynamics at a depth and accuracy that was unthinkable just a few years ago. The field of deep sequencing, which Includes the methodologies for library generation, the actual sequencing, and the downstream sequence analysis, are rapidly changing. This section of the core will actively research and optimize approaches and Informatics associated with sequencing to support the goals of the program project. Fourth, Core B will provide high-throughput RNAi screening support to the program. In conjunction with the Chandra and Young labs, personnel of Core B will work closely with the Chandra and Young labs for the generation of RNAi libraries and the actual screening.

Public Health Relevance

Enteroviruses are a major threat to public health. The High-Throughput Functional Genomics, Proteomics, and Computational Core (Core B) of this program project seeks to provide leading-edge technologies and approaches to support the overall goals of characterizing and dissecting enterovirus diversity, evolution, and pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI091575-04
Application #
8690752
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Xiao, Yinghong; Dolan, Patrick Timothy; Goldstein, Elizabeth Faul et al. (2017) Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses. Nat Commun 8:375
Stern, Adi; Yeh, Ming Te; Zinger, Tal et al. (2017) The Evolutionary Pathway to Virulence of an RNA Virus. Cell 169:35-46.e19
Menéndez-Arias, Luis; Andino, Raul (2017) Viral polymerases. Virus Res 234:1-3
Tassetto, Michel; Kunitomi, Mark; Andino, Raul (2017) Circulating Immune Cells Mediate a Systemic RNAi-Based Adaptive Antiviral Response in Drosophila. Cell 169:314-325.e13
Whitfield, Zachary J; Dolan, Patrick T; Kunitomi, Mark et al. (2017) The Diversity, Structure, and Function of Heritable Adaptive Immunity Sequences in the Aedes aegypti Genome. Curr Biol 27:3511-3519.e7
Lidsky, Peter V; Andino, Raul; Rouzine, Igor M (2017) Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections. Curr Opin Virol 23:120-124
Whitfield, Zachary J; Andino, Raul (2016) Characterization of Viral Populations by Using Circular Sequencing. J Virol 90:8950-3
Webb, Benjamin; Sali, Andrej (2016) Comparative Protein Structure Modeling Using MODELLER. Curr Protoc Bioinformatics 54:5.6.1-5.6.37
Xiao, Yinghong; Rouzine, Igor M; Bianco, Simone et al. (2016) RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence. Cell Host Microbe 19:493-503
Cimermancic, Peter; Weinkam, Patrick; Rettenmaier, T Justin et al. (2016) CryptoSite: Expanding the Druggable Proteome by Characterization and Prediction of Cryptic Binding Sites. J Mol Biol 428:709-719

Showing the most recent 10 out of 48 publications