The primary objective of the Resource for Integrated Glycotechnology is the development of multidisciplinary approaches to the solution of problems in glycobiology. A particular focus is a subset of problems related to glycosaminoglycan function. Glycosaminoglycans such as heparin, heparan sulfate, and chondroitin sulfate play important roles in modulating intracellular signaling, influencing the migration of immune cells to sites of infection, controlling angiogenesis in tumors, and regulating regeneration of neurons. They also serve as receptors for pathogenic organisms. To fulfill these roles, binding proteins interact with specific regions of these glycosaminoglycans. Understanding these interactions is an important step toward intervention in human disease, yet little information is available on the specific sequences recognized, the structural aspects of the interactions, or they way in which interactions result in cellular response. The lack of information is in part due to the extraordinary complexity of the sequences of these carbohydrate based polymers. The Resource develops technology to provide this information by combining advances in separation and synthesis of glycosaminoglycan oligomers that display binding specificity, in mass spectrometry (MS) based means of identifying oligomer structures, in nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry based means of defining three dimensional structures of complexes, in computational modeling and prediction of glycosaminoglycan-protein interactions, and in cell and biochemically based means of monitoring a biological response. The technology development is driven by selected driving biomedical projects with external collaborators. These include ones that address the function of Robo-Slit signaling in angiogenesis, the function of DLB domains in survival of the malaria parasite in placental infection, the specificity of glycosaminoglycan binding antibodies in detection of cellular abnormalities, and the regulation of immune cell migration by chemokines. Technology is disseminated through extensive training programs and additional collaborations and service functions hosted by the Resource.

Public Health Relevance

The interactions between glycosaminoglycans such as heparin, heparan sulfate, and chondroitin sulfate, and a variety of proteins involved in cellular signaling or cellular adhesion play important roles in human disease. These diseases include developmental abnormalities, cancer, coronary disease, a number of immune disorders and parasite invasion, malaria, for example. Understanding the molecular basis of specificity in these interactions is an essential component in the rational design of agents the can combat disease. The Resource for Integrated Glycotechnology develops methods that can provide this understanding.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
8P41GM103390-23
Application #
8223198
Study Section
Special Emphasis Panel (ZRG1-IMST-A (40))
Program Officer
Sheeley, Douglas
Project Start
1997-09-30
Project End
2015-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
23
Fiscal Year
2012
Total Cost
$1,975,106
Indirect Cost
$576,722
Name
University of Georgia
Department
Type
Organized Research Units
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Hsieh, Po-Hung; Thieker, David F; Guerrini, Marco et al. (2016) Uncovering the Relationship between Sulphation Patterns and Conformation of Iduronic Acid in Heparan Sulphate. Sci Rep 6:29602
Huang, Rongrong; Zong, Chengli; Venot, Andre et al. (2016) De Novo Sequencing of Complex Mixtures of Heparan Sulfate Oligosaccharides. Anal Chem 88:5299-307
Zhuo, You; Yang, Jeong-Yeh; Moremen, Kelley W et al. (2016) Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1). J Biol Chem 291:20085-95
Gao, Qi; Chen, Cheng-Yu; Zong, Chengli et al. (2016) Structural Aspects of Heparan Sulfate Binding to Robo1-Ig1-2. ACS Chem Biol 11:3106-3113
Chalmers, G; Glushka, J N; Foley, B L et al. (2016) Direct NOE simulation from long MD trajectories. J Magn Reson 265:1-9
Park, Younghee; Jowitt, Thomas A; Day, Anthony J et al. (2016) Nuclear Magnetic Resonance Insight into the Multiple Glycosaminoglycan Binding Modes of the Link Module from Human TSG-6. Biochemistry 55:262-76
Heiss, Christian; Wang, Zhirui; Black, Ian et al. (2016) Novel structural features of the immunocompetent ceramide phospho-inositol glycan core from Trichomonas vaginalis. Carbohydr Res 419:51-9
Nivedha, Anita K; Thieker, David F; Makeneni, Spandana et al. (2016) Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking. J Chem Theory Comput 12:892-901
Franks, Joshua; Glushka, John N; Jones, Michael T et al. (2016) Spin Diffusion Editing for Structural Fingerprints of Therapeutic Antibodies. Anal Chem 88:1320-7
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

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