Development and Application of Novel Glycan-Specific Reagents to Facilitate Early

新型聚糖特异性试剂的开发和应用以促进早期诊断

• 批准号: 8072313
• 负责人: DANIEL L COMINS
• 金额: $ 33.05万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072313
• 关键词: Address; Age; Age-Months; Animal Model; Animals; Biological; Biological Markers; Birds; Blood; CA-125 Antigen; Charge; Chemicals; Chemistry; Chickens; Cleaved cell; Collection; Communities; Complex Mixtures; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Dissociation; ERBB2 gene; Early Diagnosis; Electrospray Ionization; Epithelial ovarian cancer; Evaluation; Foundations; Frequencies; Goals; Health; Heart Diseases; Homeostasis; Human; Immune System Diseases; Individual; Ions; Laboratory Study; Libraries; Link; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Measures; Methods; Modeling; Molecular; Molecular Weight; Pathology; Plasma; Plasma Proteins; Play; Polysaccharides; Population; Post-Translational Regulation; Prevalence; Protein Glycosylation; Reagent; Reference Values; Regulation; Relative (related person); Research; Role; Sampling; Science; Solid; Stable Isotope Labeling; Staging; Structure; Survival Rate; Systems Biology; Techniques; Technology; Testing; Tissues; Translating; Up-Regulation; Update; Woman; analytical tool; anticancer research; base; biobank; cohort; comparative; design; improved; insight; instrumentation; ionization technique; mass analyzer; neurodevelopment; novel; open source; prognostic; response; stable isotope; time interval; tool; user-friendly; web site

DESCRIPTION (provided by applicant): Mass spectrometry is an extraordinarily powerful bio-analytical technique that has had a profound impact on our molecular understanding of human health and disease. Major advances in mass analyzer technology, dissociation techniques, and ionization methods are largely attributed to the central role that mass spectrometry plays in the field of systems biology. While mass spectrometry has evolved over the last century into a highly effective analytical tool, there are still opportunities for new advances to be made allowing an even more diverse array of biological questions to be addressed. This proposal is centered on the development and characterization of novel glycan- specific tags for biological mass spectrometry that facilitate the relative quantification of glycans cleaved from plasma proteins with increased ion abundance. The short-term objective of this proposal is to develop these novel tags and then test them using the avian model of spontaneous epithelial ovarian cancer. These results will provide a solid bio-analytical technology foundation from which our newly developed chemical tags can be applied to achieve the long-term objective of effectively elucidating glycan biomarkers for the early detection of epithelial ovarian cancer in women. Public Description of Proposed Research Mass spectrometry (MS), the science related to the "weighing of molecules", has had a profound impact on the study of human health and disease including cancer, heart disease, neural development, and auto-immune diseases. However, front-end chemistries for MS-based glycomics will be exploited to dramatically improve the ability of MS to detect and quantify glycans cleaved from plasma proteins. This will allow a more diverse array of contemporary biomedical questions to be addressed including the quantification of diagnostic and prognostic biomarkers. This proposal is squarely centered on the elucidation of a glycan-specific biomarker(s) for the early detection of epithelial ovarian cancer. PUBLIC HEALTH RELEVANCE: This proposal seeks support to develop and apply novel tags that will facilitate both global and targeted quantitative mass spectrometric analysis of N-linked glycans with significantly improved limits-of-detection. Once synthesized, the novel tags and ancillary methods will concurrently be applied to the experimental chicken model of spontaneous epithelial ovarian cancer for comparative analysis (i.e., biomarker discovery) and fully disseminated to the glycomics research community. The long-term application of these novel tags, as developed in our laboratory for this study, will be their use to elucidate glycan biomarkers for the early detection of epithelial ovarian cancer.

描述（由申请人提供）：质谱法是一种非常强大的生物分析技术，对我们对人类健康和疾病的分子理解产生了深远的影响。质量分析技术、解离技术和电离方法的重大进展主要归功于质谱在系统生物学领域中的核心作用。虽然质谱在上个世纪已经发展成为一种非常有效的分析工具，但仍然有机会取得新的进展，从而可以解决更多样化的生物学问题。该提案集中于开发和表征用于生物质谱的新型聚糖特异性标签，其促进从具有增加的离子丰度的血浆蛋白裂解的聚糖的相对定量。该提案的短期目标是开发这些新型标签，然后使用自发性上皮性卵巢癌的鸟类模型对其进行测试。这些结果将为我们新开发的化学标签提供坚实的生物分析技术基础，以实现有效阐明聚糖生物标志物的长期目标，从而早期检测女性上皮性卵巢癌。质谱（MS）是一门与“分子称重”相关的科学，对人类健康和疾病（包括癌症、心脏病、神经发育和自身免疫疾病）的研究产生了深远的影响。然而，基于MS的糖组学的前端化学将被利用，以显着提高MS检测和定量从血浆蛋白裂解的聚糖的能力。这将允许更多样化的当代生物医学问题得到解决，包括诊断和预后生物标志物的量化。该提案的核心是阐明用于早期检测上皮性卵巢癌的聚糖特异性生物标志物。 公共卫生相关性：该提案旨在支持开发和应用新型标签，这些标签将促进N-连接聚糖的全局和靶向定量质谱分析，并显着提高检测限。一旦合成，新的标签和辅助方法将同时应用于自发性上皮性卵巢癌的实验鸡模型以进行比较分析（即，生物标志物发现），并充分传播给糖组学研究界。我们实验室为这项研究开发的这些新型标签的长期应用将用于阐明上皮性卵巢癌早期检测的聚糖生物标志物。