MODULATION OF INTEGRIN FUNCTION BY CHANGES IN N-LINKED OLIGOSACCHARIDE BRANCHING

通过改变 N-连接寡糖支化来调节整合素功能

• 批准号: 7183123
• 负责人: J. Michael Pierce
• 金额: $ 0.37万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7183123
• 关键词: biomedical resource; carbohydrate structure

DESCRIPTION (provided by applicant): Glycoproteins and glycolipids have many functions in human physiology and disease and the expression of the glycans on these cell surface molecules are known to change during early embryonic development. Embryonic stem cells, derived from early embryos, can be grown in vitro and induced to differentiate into many cell types. Controlling this differentiation and producing homogeneous populations of differentiated stem cells are major challenges for the biomedical community. Development of cell markers and technology to enrich cell populations could aid significantly stem cell research. We propose to establish an Integrated Resource Center for Biomedical Glycomics that will focus on developing tools and technology to analyze in detail the glycoprotein and glycolipid expression of mouse embryonic stem cells and cells into which they differentiate. Project 1, Embryonic Stem Cell Program, will develop the tools to culture large numbers of stem cells and investigate in detail the glycans expressed on specific cell surface glycoproteins. Project 2 will develop technology to fractionate glycopeptides produced from stem cells and determine the parent proteins that express these glycans and at which sites these glycans are expressed. Project 3 will develop kinetic real-time PCR to study the expression of glycosyltransferase transcripts. Project 4 will develop Bioinformatic tools to input structural and expression data into relational databases for processing and analysis. The technology developed in this Resource will allow an understanding of how glycosylation is controlled during differentiation and will allow the development of tools to promote the use of stem cells to treat human disease. In addition, the technology will be applicable to the study of other cell types, including cancer cells that are progressing to a more invasive phenotype. This glycomics resource will result in technology development that will allow others in the scientific community to participate in glycomics research via dissemination of the new methods developed and via analytical service provided by the resource to other scientists requesting help in glycomic analyses. Training courses in the developed technologies will also be provided to the scientific community. Collaborative projects already constitute a significant amount of the proposed research and will become an increasingly important component of the developing glycomics resource.

描述（申请人提供）：糖蛋白和糖脂在人体生理和疾病中具有许多功能，已知这些细胞表面分子上聚糖的表达在早期胚胎发育过程中发生变化。胚胎干细胞来源于早期胚胎，可以在体外生长并诱导分化成多种细胞类型。控制这种分化和产生同质的分化干细胞群体是生物医学界面临的主要挑战。细胞标记和技术的发展，以丰富细胞群可以帮助显著干细胞研究。我们建议建立一个生物医学糖组学综合资源中心，专注于开发工具和技术，详细分析小鼠胚胎干细胞及其分化成的细胞的糖蛋白和糖脂表达。项目1，胚胎干细胞计划，将开发培养大量干细胞的工具，并详细研究在特定细胞表面糖蛋白上表达的聚糖。项目2将开发从干细胞中分离产生的糖肽的技术，并确定表达这些聚糖的亲本蛋白以及这些聚糖在哪些位点表达。项目3将开发动态实时PCR来研究糖基转移酶转录物的表达。项目4将开发生物信息学工具，将结构和表达数据输入关系数据库进行处理和分析。本资源中开发的技术将使人们了解在分化过程中如何控制糖基化，并将允许开发工具来促进干细胞治疗人类疾病的使用。此外，该技术将适用于其他细胞类型的研究，包括正在向更具侵袭性表型发展的癌细胞。这个糖组学资源将导致技术的发展，这将允许科学界的其他人通过传播开发的新方法和通过资源提供的分析服务来参与糖组学研究，以帮助其他科学家进行糖组学分析。还将向科学界提供有关发达技术的培训课程。合作项目已经构成了拟议研究的重要组成部分，并将成为开发糖组学资源的一个日益重要的组成部分。