Methods for determination of glycoprotein glycosylation similarities among disease states

确定疾病状态之间糖蛋白糖基化相似性的方法

基本信息

批准号：
10194553
负责人：
JOSEPH ZAIA
金额：
$ 42.08万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10194553
关键词：
Address Algorithms Atherosclerosis Autoimmune Diseases Binding Bioinformatics Biological Biological Process Biomedical Research Brain Brain region CSPG3 gene Cell Surface Proteins Cell surface Cells Chondroitin Sulfate Proteoglycan Collagen Complex Core Protein Data Data Set Disease Dissociation Electron Transport Environment Enzymes Extracellular Matrix Family Functional disorder Genes Glycopeptides Glycoproteins Growth Factor Growth Factor Receptors Heart Heparitin Sulfate Intelligence Intervention Ions Knowledge Lectin Liquid Chromatography Machine Learning Malignant Neoplasms Mechanics Mediating Methods Molecular Morphogenesis National Institute of General Medical Sciences Neurodegenerative Disorders Pathway interactions Peptides Physiological Polysaccharides Process Protein Glycosylation Proteins Proteoglycan Proteomics Receptor Protein-Tyrosine Kinases Regulation Reproducibility Role Sampling Signal Pathway Site Structure Technology Tissues aggrecan bioinformatics tool brevican cell growth data acquisition data to knowledge extracellular gene product glycoprotein structure glycoproteomics glycosylation human disease hydrophilicity neuropsychiatric disorder pathogen physical property rapid technique receptor statistics technology development technology research and development versican

项目摘要

Abstract This application addresses NIGMS PAR-17-045 “Focused Technology Research and Development (R01)”. This initiative supports projects that focus solely on development of technologies with the potential to enable biomedical research. Dysregulation of the cellular microenvironment occurs in cancers, neurodevelopmental and neuropsychiatric diseases. Known as the matrisome, the set of extracellular matrix and cell surface molecules control the availability of growth factors to cellular receptors and the mechanical-physical properties of the cell microenvironment. Currently, the limited understanding of regulation of matrisome glycosylation hinders understanding of the roles of glycosylation-dependent matrisome networks in the basic mechanisms necessary for targeted intervention of many diseases. Matrisome function depends on networks of interaction among glycosylated proteins and glycan-binding lectins. It is not possible using present proteomics and glycoproteomics methods to compare using rigorous statistics similarities of glycoproteins that differ by disease-related changes in site-specific glycosylation. We propose to develop technologies to meet this need. Present proteomics methods quantify proteins using a few representative peptides per gene product; sequence coverage for most proteins is low. Such low sequence coverage does not suffice to reconstruct the predominant glycosylated proteoforms active in a biological context. We propose to develop technologies to compare glycoprotein similarities among biological sample sets. To do this, we will develop MS acquisition and bioinformatics methods for rapid, sensitive and reproducible mapping of glycoprotein glycosylation to enable statistically rigorous comparison of glycoprotein similarities. By making these technologies available, we will enable a new level of understanding of the roles of matrisome networks in human diseases.

抽象的该申请介绍了NIGMS PAR-17-045“重点技术研发（R01）”。该计划支持仅关注技术开发的项目，并有可能使生物医学研究。细胞微环境的失调发生在癌症，神经发育和神经精神上疾病。被称为基质，细胞外基质和细胞表面分子控制生长因子对细胞受体的可用性和细胞的机械物理特性微环境。目前，对女生糖基化阻碍调节的调节有限的理解有限了解糖基化依赖性基质组网络在必要的基本机制中的作用用于许多疾病的有针对性干预。生长肌功能取决于糖基化蛋白质和聚糖结合之间相互作用的网络讲座。使用当前的蛋白质组学和糖蛋白质组学方法不可能使用严格的糖蛋白的统计相似性因疾病相关的特异性糖基化而异。我们提出开发技术以满足这一需求的建议。目前的蛋白质组学方法使用A量化蛋白质每个基因产物很少有代表性肽；大多数蛋白质的序列覆盖率很低。如此低序列覆盖范围不足以重建活跃在A中生物环境。我们建议开发技术以比较生物学之间的糖蛋白相似性样品集。为此，我们将开发MS的获取和生物信息学方法，以快速，敏感和糖蛋白糖基化的可重复映射以实现糖蛋白的统计严格比较相似之处。通过使这些技术可用，我们将使对角色的新水平了解人类疾病中的生晶网络。