RII Track-4: Characterization of LPS-induced Hsc70 ligands as a means of defining the role of C-linked glycosylation in innate immunity.

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Non-technical DescriptionThe immune system's response to infection and autoimmune diseases includes inflammation that is controlled by specific chemicals, and the production and function of many of which is not clearly understood. This project supports the PI for a six-month period in the Complex Carbohydrate Research Center (CCRC) at the University of Georgia. The CCRC possesses unparalleled research expertise and analytical instrumentation focused on the biochemical study of carbohydrate molecules, including those involved in inflammation. This fellowship allows the PI access to the expertise and the advanced instrumentation capability of CCRC, and he will bring that expertise back to Marshall University. Characterization of these molecules in the context of inflammation will provide important information about the causes and control of inflammation, including inflammation involved in autoimmune disease. Technical DescriptionThis fellowship will aid in bolstering the research capacity in West Virginia by supporting the PI's efforts to use the resources at the CCRC to evaluate protein regulators of the innate immune response. Providing access to the facilities and expertise at the CCRC will enable the PI to establish a vibrant research program studying the role of glycosylation in inflammation in West Virginia. It has been shown that C-glycosylated peptides enhance the production of the proinflammatory cytokine TNFα, secreted from lipopolysaccharide (LPS)-stimulated macrophage-like cells. This indicates that a currently unknown regulatory mechanism involving C-linked glycosylation is crucial for activation of the LPS/TLR4 pathway. As TNFα is the central cytokine produced in the inflammatory response, defining how C-linked glycosylation regulates this cytokine response is critical in properly addressing its dysregulation. Dysregulation of TNFα is inherent to inflammatory diseases such as Crohn?s disease, sepsis, rheumatoid arthritis, and metabolic syndrome.