Protein-glycan interactions in the vascular system

描述（由申请人提供）：我们的计划项目资助的更新提案继续采用跨学科的方法来研究血管系统中蛋白质-聚糖相互作用的功能。这三个主题相关的项目由具有互补专业知识和强大的合作研究记录的研究人员领导。项目1使用基因靶向小鼠研究血管系统中粘附和信号分子的相互作用。重点是调节选择素与其糖缀合物配体的相互作用的过程，这是炎症和血栓形成期间的关键早期反应。将研究选择素、选择素配体或信号蛋白表达改变的小鼠。项目2研究半乳糖凝集素与白细胞的相互作用。主要的主题包括定义的聚糖结构识别的每一个半乳糖凝集素，磷脂酰丝氨酸对活化的中性粒细胞无凋亡的新的曝光的信号传导机制，和半乳糖凝集素在体内调节炎症的生物学作用。项目3研究0-糖蛋白podoplanin如何维持分离的血管和淋巴管，血管和淋巴管的混合如何导致疾病，以及0-糖基化如何在体外和体内调节podoplanin的功能。由于知识上的重叠主题以及试剂和方法的共享，这些项目之间具有异常高的协同作用。一个行政核心加强互动，特别是通过维护一个服务器，用于项目之间的数据交换，并通过计算机支持处理图像和其他复杂数据。所获得的数据将增强我们对凝集素和糖缀合物在炎症、血栓形成和血管发育过程中的功能的理解。这一信息可能为治疗心脏病发作、中风和其他心血管疾病提供新的方法。

DESCRIPTION (provided by applicant): This renewal proposal for our Program Project Grant continues to employ an interdisciplinary approach to study the functions of protein-glycan interactions in the vascular system. The three thematically related projects are led by investigators with complementary expertise and a strong published record of collaborative research. Project 1 uses gene-targeted mice to study the interplay of adhesion and signaling molecules in the vasculature. The emphasis is on processes that regulate the interactions of selectins with their glycoconjugate ligands, a critical early response during inflammation and thrombosis. Mice with altered expression of selectins, selectin ligands, or signaling proteins will be studied. Project 2 studies the interactions of galectins with leukocytes. Major themes include the defining the glycan structures recognized by each galectin, the signaling mechanisms for the novel exposure of phosphatidylserine on activated neutrophils without apoptosis, and the biological roles of galectins in regulating inflammation in vivo. Project 3 studies how the 0-glycoprotein podoplanin maintains separated blood and lymphatic vessels, how mixing of blood and lymphatic vessels contributes to disease, and how 0-glycosylation regulates the functions of podoplanin in vitro and in vivo. There is unusually high synergy among the projects that results from the intellectually overlapping themes and the sharing of reagents and methods. An administrative core cements the interactions, in particular through maintenance of a server for data exchange among the projects and through computer support for processing images and other complex data. The data obtained will enhance our understanding of the functions of lectins and glycoconjugates during inflammation, thrombosis, and vascular development. This information may suggest new approaches to treat heart attacks, strokes, and other cardiovascular disorders.