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 #
7P41GM103694-04
Application #
9207639
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sheeley, Douglas
Project Start
2013-08-01
Project End
2018-06-30
Budget Start
2015-09-01
Budget End
2016-06-30
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
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Behrens, Anna-Janina; Duke, Rebecca M; Petralia, Laudine M C et al. (2018) Changes in canine serum N-glycosylation as a result of infection with the heartworm parasite Dirofilaria immitis. Sci Rep 8:16625
Sharma, Mamta; Hegde, Prajna; Hiremath, Kavita et al. (2018) Purification, characterization and fine sugar specificity of a N-Acetylgalactosamine specific lectin from Adenia hondala. Glycoconj J 35:511-523
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Kudelka, Matthew R; Nairn, Alison V; Sardar, Mohammed Y et al. (2018) Isotopic labeling with cellular O-glycome reporter/amplification (ICORA) for comparative O-glycomics of cultured cells. Glycobiology 28:214-222
Mahajan, Sonal; Ramya, T N C (2018) Nature-inspired engineering of an F-type lectin for increased binding strength. Glycobiology 28:933-948
Hu, Liya; Sankaran, Banumathi; Laucirica, Daniel R et al. (2018) Glycan recognition in globally dominant human rotaviruses. Nat Commun 9:2631
Sardar, Mohammed Y R; Mandhapati, Appi Reddy; Park, Simon et al. (2018) Convergent Synthesis of Sialyl LewisX- O-Core-1 Threonine. J Org Chem 83:4963-4972

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