Time-Course Proteomics to Uncover the Mechanism and Nature of Aging in C. elegans

时间过程蛋白质组学揭示线虫衰老的机制和本质

• 批准号: 8389573
• 负责人: Jarrett David Egertson
• 金额: $ 3.06万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8389573
• 关键词: Adult; Age; Aging; Aging-Related Process; Alleles; Animals; Biological Models; Caenorhabditis elegans; Caloric Restriction; Collection; Computer software; Data; Development; Eukaryota; Event; Germ-Line Mutation; Human; Insulin; Insulin-Like Growth Factor I; Ions; Life; Longevity; Mass Spectrum Analysis; Measurement; Methods; Metric; Modeling; Molecular; Mutation; Nature; Nematoda; Output; Pathway interactions; Peptides; Process; Proteins; Proteome; Proteomics; Regulation; Sampling; Sampling Biases; Scheme; Sensitivity and Specificity; Staging; Technology; Testing; Time; Transcript; Work; Writing; forkhead protein; improved; insight; mass spectrometer; molecular marker; mutant; novel; offspring; protein complex; protein profiling; public health relevance; receptor; tandem mass spectrometry; tool

DESCRIPTION (provided by applicant): This project aims to enhance understanding of the aging process through the study of the long-lived Caenorhabditis elegans daf-2 mutant. A data-independent-acquisition mass spectrometry scheme will be developed to enable a high-sensitivity, high-dynamic range, quantifiable analysis of the C. elegans proteome throughout the aging process. To this end, software will be written to deconvolute MS/MS spectra derived from the fragmentation of multiple precursors. C. elegans, with a germ-line mutation to avoid development of offspring, will be synchronized and grown. Strains that will be grown include a glp-4 strain, a glp-4; daf-2 mutant strain, and a daf-16 glp-4; daf-2 mutant strain. The protein profile of these strains will be analyzed over time to uncover new components of the aging pathway as well as generate a metric for "molecular age". The relationship between "molecular age" and chronological age will be determined.

描述（由申请人提供）：本项目旨在通过研究长寿的秀丽隐杆线虫daf-2突变体，提高对衰老过程的认识。将开发一种数据独立采集质谱方案，以便在整个衰老过程中对秀丽隐杆线虫蛋白质组进行高灵敏度、高动态范围、可量化的分析。为此，将编写软件来反卷积来自多个前体碎片的MS/MS谱。秀丽隐杆线虫，通过种系突变来避免后代的发育，将同步生长。将要培养的菌株包括glp-4菌株，glp-4；Daf-2突变株和daf-16 glp-4；Daf-2突变株。随着时间的推移，这些菌株的蛋白质谱将被分析，以揭示衰老途径的新成分，并产生“分子年龄”的度量。“分子年龄”和实足年龄之间的关系将被确定。