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
Hurwitz, Amy M; Huang, Wanzhi; Estes, Mary K et al. (2017) Deep sequencing of phage-displayed peptide libraries reveals sequence motif that detects norovirus. Protein Eng Des Sel 30:129-139
Yu, Huimin; Hasan, Nesrin M; In, Julie G et al. (2017) The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology. Annu Rev Physiol 79:291-312
Ramani, Sasirekha; Neill, Frederick H; Ferreira, Jennifer et al. (2017) B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine. Clin Vaccine Immunol 24:
Cortes-Penfield, Nicolas W; Ramani, Sasirekha; Estes, Mary K et al. (2017) Prospects and Challenges in the Development of a Norovirus Vaccine. Clin Ther 39:1537-1549
Zou, Winnie Y; Blutt, Sarah E; Crawford, Sue E et al. (2017) Human Intestinal Enteroids: New Models to Study Gastrointestinal Virus Infections. Methods Mol Biol :
Shanker, Sreejesh; Hu, Liya; Ramani, Sasirekha et al. (2017) Structural features of glycan recognition among viral pathogens. Curr Opin Struct Biol 44:211-218
Hurwitz, Amy M; Huang, Wanzhi; Kou, Baijun et al. (2017) Identification and Characterization of Single-Chain Antibodies that Specifically Bind GI Noroviruses. PLoS One 12:e0170162
Foulke-Abel, Jennifer; In, Julie; Yin, Jianyi et al. (2016) Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology. Gastroenterology 150:638-649.e8
Mills, Melody; Estes, Mary K (2016) Physiologically relevant human tissue models for infectious diseases. Drug Discov Today 21:1540-1552
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

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