The Protein and Small Molecule Chemistry Core (Core C) will provide instrumentation, expertise and service related to the cloning, expression and purification of viral proteins and virus-like-particles (VLPs) as needed by each of the three major projects. In addition, the Core will provide chemical synthesis support for the small molecule inhibitor discovery efforts proposed in Projects 1 and 3. This core will provide the following specific functions: (1) cloning of wild-type and mutant genes encoding viral proteins into bacterial and insect expressions systems;(2) purification of viral proteins;(3) expression, purification and characterization of VLPs;(4) quantitation of interactions with antibodies, polysaccharides and small molecules;(5) synthesis of peptide arrays for diagnostics assays proposed in Project 1;(6) synthesis of small molecules to examine structure-activity relationships and increase potency of candidate molecules developed in Projects 1 and 3.

Public Health Relevance

The Protein and Small Molecule Chemistry Core will facilitate the discovery and development of molecules to be used as diagnostics or therapeutics for norovirus infections. The development of new diagnostics and therapeutics would have a positive impact on public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI057788-10
Application #
8636979
Study Section
Special Emphasis Panel (ZAI1-GPJ-M)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
10
Fiscal Year
2014
Total Cost
$266,439
Indirect Cost
$92,863
Name
Baylor College of Medicine
Department
Type
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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Ettayebi, Khalil; Crawford, Sue E; Murakami, Kosuke et al. (2016) Replication of human noroviruses in stem cell-derived human enteroids. Science 353:1387-1393
Prasad, Bv Venkataram; Shanker, Sreejesh; Muhaxhiri, Zana et al. (2016) Antiviral targets of human noroviruses. Curr Opin Virol 18:117-25
Shanker, Sreejesh; Czakó, Rita; Sapparapu, Gopal et al. (2016) Structural basis for norovirus neutralization by an HBGA blocking human IgA antibody. Proc Natl Acad Sci U S A 113:E5830-E5837
Ramani, Sasirekha; Neill, Frederick H; Opekun, Antone R et al. (2015) Mucosal and Cellular Immune Responses to Norwalk Virus. J Infect Dis 212:397-405
Kou, Baijun; Huang, Wanzhi; Neill, Frederick H et al. (2015) Norovirus Antigen Detection with a Combination of Monoclonal and Single-Chain Antibodies. J Clin Microbiol 53:3916-8
Ye, X; Van, J N; Munoz, F M et al. (2015) Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients. Am J Transplant 15:1874-81
Henning, Susan J; Estes, Mary K (2015) Women in Science: Hints for Success. Gastroenterology 149:10-3
Crawford, Sue E; Ajami, Nadim; Parker, Tracy Dewese et al. (2015) Mapping broadly reactive norovirus genogroup I and II monoclonal antibodies. Clin Vaccine Immunol 22:168-77
Hesse, Shayla; Neill, Frederick H; Estes, Mary K et al. (2015) Serological Responses to a Norovirus Nonstructural Fusion Protein after Vaccination and Infection. Clin Vaccine Immunol 23:181-3

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