Here we propose to establish a """"""""National Center for Functional Glycomics"""""""" (NCFG) that is focused on 5 major objectives;Technology Research and Development (TR&D);Driving Biomedical Projects (DBPs) tied to TR&D Projects;Collaborative Services;Training;and Dissemination of Technologies and Research Discoveries. The development of this application is an outgrowth of the very successful leadership provided by the Glycomics Center at Emory University School of Medicine, which housed the Protein-Glycan Interaction Core (Core H) of the successful Consortium for Functional Glycomics (CFG), a unique NIGMS-funded resource from 2001-2011 that has been utilized by hundreds of investigators worldwide. The Center's applications of the CFG's Defined Glycan Microarray, which has received >800 requests for analyses in the past 8 years, has revolutionized studies on protein-glycan interactions. Defined glycan microarrays have become the benchmark in studying the glycan-binding specificity of lectins, antibodies, and viruses, which for this grant application are termed glycan-binding proteins (GBPs). The value of immobilized glycans in studying GBPs and functional glycomics is evidenced by the collaborations already established in the Center with over 600 Principal Investigators worldwide, resulting in >350 peer-reviewed publications in the past 8 years. Over the past several years, the members of the Glycomics Center at Emory, who are the lead investigators in this proposed NCFG, have provided innovative leadership in developing technologies for studying the functions of cellular glycomes and for glycomic analyses. In the 3 TR&D Projects proposed for this NCFG, we will 1) expand glycan microarray technologies, 2) develop """"""""Shotgun Glycomics"""""""" as a general method for studying natural cell-derived glycan recognition, and 3) develop different glycan display technologies, as well as cellular avatars - particles that represent cellular glycomes in unique presentations. The DBPs include studies on the roles of glycans in microbial and viral infections, glycans and GBPs in cell adhesion, innate and adaptive immune responses, and recognition factors within the glycocalyx that contribute to GBP interactions. The NCFG will use these advances to drive a strong Collaborative Service component to aid the biomedical research community in the using and developing of glycan microarrays and other approaches to explore glycan recognition. We will offer a robust Training program, as well as initiate multiple venues and strategies to Disseminate the technological and scientific developments in the NCFG.

Public Health Relevance

This proposed National Center for Functional Glycomics (NCFG) will provide a unique technological and biological resource for studying the structure and function of human and animal glycomes, through innovative glycan microarray technologies, and novel glycan presentations, as well as explore an important set of driving biological projects that exploit the technology developments. The NCFG will provide a unique national resource in collaboration, training, and dissemination of results in the field that will elevate and propel important advances in glycomics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103694-02
Application #
8711517
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Program Officer
Sheeley, Douglas
Project Start
2013-08-01
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$1,088,787
Indirect Cost
$307,512
Name
Emory University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Noll, Alexander J; Gourdine, Jean-Philippe; Yu, Ying et al. (2016) Galectins are human milk glycan receptors. Glycobiology 26:655-69
Agravat, Sanjay B; Song, Xuezheng; Rojsajjakul, Teerapat et al. (2016) Computational approaches to define a human milk metaglycome. Bioinformatics 32:1471-8
Song, Xuezheng; Ju, Hong; Lasanajak, Yi et al. (2016) Oxidative release of natural glycans for functional glycomics. Nat Methods 13:528-34
Mickum, Megan L; Prasanphanich, Nina Salinger; Song, Xuezheng et al. (2016) Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray. Infect Immun 84:1371-86
Khatri, Kshitij; Klein, Joshua A; White, Mitchell R et al. (2016) Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions. Mol Cell Proteomics 15:1895-912
Noll, Alexander J; Yu, Ying; Lasanajak, Yi et al. (2016) Human DC-SIGN binds specific human milk glycans. Biochem J 473:1343-53
Alymova, Irina V; York, Ian A; Air, Gillian M et al. (2016) Glycosylation changes in the globular head of H3N2 influenza hemagglutinin modulate receptor binding without affecting virus virulence. Sci Rep 6:36216
Hewitson, James P; Nguyen, D Linh; van Diepen, Angela et al. (2016) Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. Int J Parasitol 46:157-70
Kudelka, Matthew R; Antonopoulos, Aristotelis; Wang, Yingchun et al. (2016) Cellular O-Glycome Reporter/Amplification to explore O-glycans of living cells. Nat Methods 13:81-6
Brazil, Jennifer C; Sumagin, Ronen; Cummings, Richard D et al. (2016) Targeting of Neutrophil Lewis X Blocks Transepithelial Migration and Increases Phagocytosis and Degranulation. Am J Pathol 186:297-311

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