Role of polysialic acid in sex-specific immune responses

聚唾液酸在性别特异性免疫反应中的作用

• 批准号: RGPIN-2021-02888
• 负责人: Willis, Elizabeth
• 金额: $ 2.99万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744861
• 关键词: Role; polysialic; acid; sex; specific

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.

聚唾液酸 (polySia) 是一种有效的免疫调节聚糖，由长的、线性的唾液酸残基链组成，这些残基附着在健康成人的一组有限的细胞表面糖蛋白上。 PolySia 能够促进细胞迁移并减弱免疫反应。然而，polySia 功能的分子细节尚未阐明，很大程度上是由于缺乏研究 polySia 生物学所需的分析工具。我们最近开发了两种可用于研究 polySia 的分析工具。其中一个工具是一种新颖的 ELISA，用于定量血清中的 PolySia，并使用它，我们发现男性的 PolySia 浓度高于女性。我们对有效免疫调节聚糖浓度的性别差异的影响感兴趣，并且了解这些差异的原因和结果构成了我的研究计划的基础。该提案的目标是开发工具来实现该研究计划，方法是：1) 确定血清 PolySia 中性别差异的来源，2) 开发识别多唾液酸化蛋白的方法，3) 开发识别 PolySia 受体的方法。 这项资助中描述的方法将改变我们研究 polySia 功能分子基础的能力。