Complex carbohydrates or glycans are involved in almost every physiological or pathological process. Advances in understanding the biological roles played by glycans, along with the factors that influence or alter their functions will provid important avenues for the development of new therapeutics, and diagnostics. In recognition of opportunities to advance the impact of glycoscience on human health, we have assembled a team of five senior investigators that will work cooperatively on three related research projects to exploit unique capabilities of a Core to produce recombinant mammalian glycosyltransferases. The research projects will 1) study biochemical and structural aspects of glycosyltransferase to define their acceptor specificities at a molecular and structural level 2) exploit the enzymes in a novel chemoenzymatic approach to provide glycans for structure activity relationship studies, aid in the development of the next generation of glycan microarray and as analytical standards;3) develop sugar nucleotide donors modified by a chemical reporters to label subsets of glycoconjugates for visualization, capture and identification of glycans in cellular models of disease. The three projects have high synergy. Each requires a relatively large panel of glycosyltransferases that will be produced by a core. In addition, they will generate reciprocal knowledge and resources. Project 1 and 3 will perform complementary studies to uncover glycosyl acceptor specificities of glycosyltransferases. Information about glycosyl acceptor specificities of glycosyltransferases will be employed by Project 2 to prepare glycans that otherwise are not accessible by chemo-enzymatic synthesis. Project 2 will generate synthetic glycans that will be employed by Project 1 for in depth studies of glycosyl acceptor specificities. Structural studies by Project 1 will provide important information for project to design of sugar nucleotide donors modified with a chemical reporter for cellular studies in the context of human disease.

Public Health Relevance

Glycans play key roles in almost every biological process and are involved in every major disease. In recognition of opportunities to advance the impact of glycoscience on human health, this program project will study important aspect of the enzymes that biosynthesize these important biopolymers. The enzymes will also be employed to synthesize glycans of biomedical importance and used to monitor glycan trafficking and analysis in the context of human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM107012-02
Application #
8740506
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Marino, Pamela
Project Start
2013-09-24
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Georgia
Department
Type
Organized Research Units
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602
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