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.
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.
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