Glycosaminoglycans (GAGs) are complex polysaccharides found in abundance at the cell-extracellular matrix (ECM) interface of eukaryotic cells. There has been a paradigm shift in understanding the importance of the dynamic nature of the cell-ECM interactions (historically the ECM was considered an inert material that hydrated the cells) in influencing phenotype at cellular and higher order tissue and organ levels. At the heart of this paradigm are the specific interactions between the chemically heterogeneous GAGs and numerous proteins in the extracellular environment. Thus, understanding the structure-function relationship of GAGs has gained importance both as a fundamental field and for its potential in identification of novel therapeutic targets. However, progress towards this goal has been limited in the past due to the polydispersity and chemical heterogeneity of GAGs that posed numerous challenges for their isolation and characterization. For several years, we have focused our efforts in addressing these challenges to develop enzymatic tools for predictable depolymerization of GAGs to decode their sequence information as well as sensitive analytical techniques to accurately detect and characterize extremely small amounts of GAGs available from cells or tissues. Focusing on the 2 important classes of GAGs viz. HSGAGs and CSGAGs we have successfully demonstrated the utility of our tools to develop rapid and robust technologies for sequencing GAGs. In this study we seek to expand on the development of our tools to focus on biochemical and biological aspects of HSGAG and CSGAG structure-function relationships. Finally, we seek to develop a database platform to capture and disseminate information and data pertaining to GAG structure function relationships which is a novel approach in the context of the GAG research area. We believe that our study would truly accelerate the progress of understanding GAG-structure-function relationships in fundamental biological processes-a research area that is gaining increasing importance.
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