Role of polysialic acid in sex-specific immune responses

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Polysialic acid (polySia) is a potent immunomodulatory glycan comprised of long, linear chains of sialic acid residues which are attached to a limited set of cell surface glycoproteins in healthy human adults. PolySia enables cell migration and attenuates the immune response. However, the molecular details of polySia function have not yet been elucidated, in large part due to the lack of analytical tools required to study polySia biology. We have recently developed two analytical tools which can be used to study polySia. One of these tools was a novel ELISA for quantifying polySia in serum and using it, we discovered that males have higher concentrations of polySia than females. We are interested in the implications of sex differences in concentration of a potent immunomodulatory glycan and understanding the causes and outcomes of these differences forms the basis of my research program. The goal of this proposal is to develop tools to enable this research program by 1) identifying the source of sex differences in serum polySia, 2) developing methodology to identify polysialylated proteins, and 3) developing methodology to identify polySia receptors. The methodology described in this grant will transform our ability to study the molecular basis for polySia function.