Methods for measuring matrisome molecule similarity during disease processes

测量疾病过程中基质体分子相似性的方法

• 批准号: 10330789
• 负责人: JOSEPH ZAIA
• 金额: $ 27.23万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10330789
• 关键词: Age; Aging; Animals; Award; Binding; Bioinformatics; Biological; Brain; Brain region; Cell Surface Proteins; Cells; Clinical Trials; Cytoplasmic Granules; Data; Detection; Disease; Extracellular Matrix; Focus Groups; Funding; Glycoproteins; Glycosaminoglycans; Goals; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Methods; Molecular; National Institute of General Medical Sciences; Neurodegenerative Disorders; Neurologic; Peptides; Periodicity; Physiological; Physiology; Polysaccharides; Process; Proteins; Proteoglycan; Proteomics; Research; Research Personnel; Sampling; Serine; Signal Transduction; Slide; Sulfate; Surface; Technology; Tissues; Water; analytical method; antibody detection; detection method; glycoprotein structure; glycoproteomics; glycosylation; instrument; ion mobility; liquid chromatography mass spectrometry; normal aging; pathogen; programs; Age; Aging; Animals; Award; Binding; Bioinformatics; Biological; Brain; Brain region; Cell Surface Proteins; Cells; Clinical Trials; Cytoplasmic Granules; Data; Detection; Disease; Extracellular Matrix; Focus Groups; Funding; Glycoproteins; Glycosaminoglycans; Goals; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Methods; Molecular; National Institute of General Medical Sciences; Neurodegenerative Disorders; Neurologic; Peptides; Periodicity; Physiological; Physiology; Polysaccharides; Process; Proteins; Proteoglycan; Proteomics; Research; Research Personnel; Sampling; Serine; Signal Transduction; Slide; Sulfate; Surface; Technology; Tissues; Water; analytical method; antibody detection; detection method; glycoprotein structure; glycoproteomics; glycosylation; instrument; ion mobility; liquid chromatography mass spectrometry; normal aging; pathogen; programs

Project Summary/Abstract: The application responds to NIGMS PAR-19-367 “Maximizing Investigators' Research Award (R35 - Clinical Trial Optional)” My research group focused initially on analytical methods for glycosaminoglycans (GAGs). These linear, sulfated polysaccharides are attached to serine residues of proteoglycan molecules found on cellular surfaces, in intracellular granules and in extracellular matrices. Binding interactions between GAGs and proteins are central to aspects of animal physiology including cellular signaling, the cellular microenvironment, and host- host, and host-pathogen recognition. My group developed methods for liquid chromatography-mass spectrometry analysis and sequencing of GAGs, extraction of GAGs from wet tissue and tissue slides, and bioinformatics programs for interpretation of GAG MS and tandem MS data. We then pioneered methods to acquire glycomics (GAGs and N-glycans) and proteomics from biospecimen tissue slides. We applied these methods to study of neurological aging, cancer, neurodevelopmental, and neurodegenerative diseases. As funded through NIGMS R01GM133963 “Methods for determination of glycoprotein glycosylation similarities among disease states”, my group is developing analytical and bioinformatics methods for glycoproteomics of the extracellular matrix molecules (known as the matrisome) of brain. The primary focus has been on glycoproteomics MS acquisition methods and bioinformatics for rigorous statistical determination of molecular similarities for matrisome molecules and how these change during normal aging versus disease processes. I now propose to expand our brain glycoproteomics molecular similarity scope to include characterization of GAGs that modify specific matrisome molecules. Our goals will be to provide information on the pathophysiological changes to matrisome molecules that escape detection using traditional antibody-based detection methods. We will employ a new Omnitrap platform to characterize multiply glycosylated peptides and peptides modified with GAG chains. We will also exploit the capabilities of ion mobility for measuring molecular similarities from glycoproteomics data using a Waters Cyclic ion mobility-mass spectrometry instrument. We will demonstrate these approaches by comparing matrisome molecular similarity among brain regions and as a function of age.

项目摘要/摘要： 申请响应对NIGMS PAR-19-367“最大化研究人员的研究奖（R35-临床） 试用可选）” 我的研究小组最初关注糖胺聚糖（GAGS）的分析方法。这些线性， 硫酸化的多糖附着在细胞表面上发现的蛋白聚糖分子的丝氨酸残留物上， 在细胞内颗粒和细胞外物质中。插孔和蛋白质之间的结合相互作用是 动物生理学各个方面的中心，包括细胞信号传导，细胞微环境和宿主 - 宿主和宿主病原体识别。我的小组开发了液相色谱质量的方法 光谱法分析和插科打术，从湿组织和组织载玻片中提取插孔以及 用于解释GAG MS和TANDEM MS数据的生物信息学计划。然后，我们开创了方法 获取糖果科学（GAGS和N-聚糖）和蛋白质组学，从生物测量组织载玻片中获取。我们应用了这些 研究神经衰老，癌症，神经发育和神经退行性疾病的方法。 通过NIGMS R01GM133963资助，“确定糖蛋白糖基化相似性的方法 在疾病状态中”，我的小组正在开发分析和生物信息学方法，用于糖蛋白质组学 大脑的细胞外基质分子（称为基质组）。主要重点一直在 糖蛋白质组学MS采集方法和生物信息学用于严格统计分子的确定 生成体分子的相似性，以及在正常衰老与疾病过程中它们如何变化。 我现在建议扩大我们的大脑糖蛋白质组学分子相似性范围，包括 修改特定基质组分子的插科打。我们的目标是提供有关 使用传统抗体逃脱检测的基质分子的病理生理变化 检测方法。我们将采用一个新的Omnitrap平台来表征多糖基化的Petides和 用插科打链修饰的肽。我们还将利用离子迁移率测量分子的能力 使用Waters Cyclic Ion迁移率质谱仪器来获得糖蛋白质组学数据的相似性。我们 将通过比较大脑区域之间的源组分子相似性和作为一个 年龄的功能。