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 #
5P41GM103390-25
Application #
8611933
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
2014-02-01
Budget End
2015-01-31
Support Year
25
Fiscal Year
2014
Total Cost
$1,594,854
Indirect Cost
$495,032
Name
University of Georgia
Department
Type
Organized Research Units
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Xie, Boer; Sood, Amika; Woods, Robert J et al. (2017) Quantitative Protein Topography Measurements by High Resolution Hydroxyl Radical Protein Footprinting Enable Accurate Molecular Model Selection. Sci Rep 7:4552
Cliff, Timothy S; Wu, Tianming; Boward, Benjamin R et al. (2017) MYC Controls Human Pluripotent Stem Cell Fate Decisions through Regulation of Metabolic Flux. Cell Stem Cell 21:502-516.e9
Hanes, Melinda S; Moremen, Kelley W; Cummings, Richard D (2017) Biochemical characterization of functional domains of the chaperone Cosmc. PLoS One 12:e0180242
Benedetti, Elisa; Pu?i?-Bakovi?, Maja; Keser, Toma et al. (2017) Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway. Nat Commun 8:1483
Gao, Qi; Chalmers, Gordon R; Moremen, Kelley W et al. (2017) NMR assignments of sparsely labeled proteins using a genetic algorithm. J Biomol NMR 67:283-294
Turney, Toby; Pan, Qingfeng; Sernau, Luke et al. (2017) O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis. J Phys Chem B 121:66-77
Zhuo, You; Cordeiro, Ciro D; Hekmatyar, S Khan et al. (2017) Dynamic nuclear polarization facilitates monitoring of pyruvate metabolism in Trypanosoma brucei. J Biol Chem 292:18161-18168
Sheikh, M Osman; Halmo, Stephanie M; Patel, Sneha et al. (2017) Rapid screening of sugar-nucleotide donor specificities of putative glycosyltransferases. Glycobiology 27:206-212
Chiu, Yulun; Schliekelman, Paul; Orlando, Ron et al. (2017) A Multivariate Mixture Model to Estimate the Accuracy of Glycosaminoglycan Identifications Made by Tandem Mass Spectrometry (MS/MS) and Database Search. Mol Cell Proteomics 16:255-264
Rahman, Kazi; Mandalasi, Msano; Zhao, Peng et al. (2017) Characterization of a cytoplasmic glucosyltransferase that extends the core trisaccharide of the Toxoplasma Skp1 E3 ubiquitin ligase subunit. J Biol Chem 292:18644-18659

Showing the most recent 10 out of 203 publications