A Research Program on Advancing Biomedical Glycoproteomics

推进生物医学糖蛋白组学研究计划

• 批准号: 10466825
• 负责人: ERIC D DODDS
• 金额: $ 36.87万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-05 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10466825
• 关键词: Affect; Biological Markers; Biomedical Research; Complex; Development; Disease; Goals; Health; Human; Investments; Mass Spectrum Analysis; Metabolic; Molecular; Pattern; Polysaccharides; Process; Protein Glycosylation; Proteins; Research; Site; Spectrometry; Techniques; Time; Translating; United States National Institutes of Health; Work; analytical tool; base; biomarker discovery; glycoproteomics; innovation; interest; ion mobility; link protein; new technology; novel; programs; protein function; protein structure; protein structure function; sugar; tandem mass spectrometry; tool

PROJECT SUMMARY / ABSTRACT The biomedical relevance of disease-related alterations in protein glycosylation has been recognized for some time. However, significant challenges remain in translating these observations into robust disease biomarkers, and in establishing a detailed molecular understanding of how altered protein glycosylation affects a diverse variety of biomolecular interactions and protein structure / function interplays. Because protein glycosylation is the end result of complex non-template-driven biosynthetic processes, a protein glycoform profile is exquisitely sensitive to metabolic irregularities, including those that accompany disease. For these reasons, the detailed molecular characterization of protein glycosylation is of great biomedical interest in the context of disease biomarker discovery, and for the purpose of relating disease-induced alterations of protein glycosylation to protein function. Essential to such endeavors are powerful analytical techniques that can determine the compositions and structures of protein-linked glycans and their sites of protein attachment in complex and heterogeneous mixtures. This application to the MIRA program requests support of a research program dedicated to the advancement of biomedical glycoproteomics through the development, application, and dissemination of mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry based tools for interrogating the glycoproteome and determining site-specific protein glycoforms. The goals of this program are consonant with current NIH priorities, including the recent calls for increased investment in early stage development of new technologies for biomedical research and ongoing initiatives to catalyze advancements in glycoscience. The new technologies that will result from this work will be generalizable and thus applicable to the elucidation of site-specific protein glycoform patterns in an eclectic array of biomedically-relevant contexts.

项目概要/摘要 与疾病相关的蛋白质糖基化改变的生物医学相关性已被认识到 某个时间。然而，将这些观察结果转化为强大的疾病仍然存在重大挑战 生物标志物，并建立对蛋白质糖基化改变如何影响的详细分子理解 多种生物分子相互作用和蛋白质结构/功能相互作用。因为蛋白质 糖基化是复杂的非模板驱动的生物合成过程的最终结果，是一种蛋白质糖型谱 is exquisitely sensitive to metabolic irregularities, including those that accompany disease.由于这些原因， 蛋白质糖基化的详细分子特征在生物医学领域具有重大意义 disease biomarker discovery, and for the purpose of relating disease-induced alterations of protein glycosylation 对蛋白质功能。这些努力的关键是强大的分析技术，可以确定 蛋白质连接聚糖的组成和结构及其在复杂和中的蛋白质附着位点 异质混合物。此 MIRA 计划申请请求研究计划支持 致力于通过开发、应用和推广生物医学糖蛋白组学 传播基于质谱、串联质谱和离子迁移谱的工具 询问糖蛋白质组并确定位点特异性蛋白质糖型。该计划的目标是 符合 NIH 当前的优先事项，包括最近呼吁增加早期阶段的投资 生物医学研究新技术的开发以及促进生物医学进步的持续举措 糖科学。这项工作产生的新技术将是可推广的，因此适用于 在一系列不拘一格的生物医学相关背景中阐明位点特异性蛋白质糖型模式。