Proteomic Pipelines for the Quantification of Abundance and Turnover of Post-Translationally Modified Proteins in Aging Studies

用于量化衰老研究中翻译后修饰蛋白质的丰度和周转率的蛋白质组管道

• 批准号: 10688782
• 负责人: Nathan Basisty
• 金额: $ 5.77万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688782
• 关键词: Acylation; Age; Aging; Area; Autophagocytosis; Biological; Clinic; Clinical Research; Collaborations; Communities; Complex; Computer software; Data Analyses; Development; Disease; Goals; Human; Institutional Review Boards; Intervention; Journals; Label; Link; Manuscripts; Measurement; Measures; Metabolic; Methods; Mitochondria; Modeling; Mus; Muscular Atrophy; Nerve Degeneration; Non-Insulin-Dependent Diabetes Mellitus; Pathology; Post-Translational Protein Processing; Preparation; Process; Proteins; Proteome; Proteomics; Protocols documentation; Research; Role; Scientist; Software Tools; System; Tissues; Translations; Ubiquitin; Universities; Washington; Work; age related; aging brain; computational platform; computerized tools; multicatalytic endopeptidase complex; novel; open source; protein aggregation; protein degradation; protein function; proteostasis; sarcopenia; skeletal muscle wasting; therapeutic target; tool; user-friendly

We have made significant progress toward the first goal of developing of a software tool within the Skyline proteomics platform. We have worked with the Skyline core development team (Michael MacCoss and Brendan MacLean at the University of Washington in Seattle) to develop a software tool that is now available in the Skyline External Tool store. A manuscript describing this work has been accepted in the Journal of Proteome Research. Toward our second objective, we have conducted the first mouse study utilizing this tool to determine which proteins are turned over at different rates during muscle atrophy in collaboration with Dr. Christopher Adams lab at the Mayo Clinic in Rochester, MN. In the analysis of this data with our turnover tool, we have identified a subset of mitochondrial and myofibrillar proteins with altered turnover that are associated with the development of age-related skeletal muscle atrophy. This manuscript is in preparation. We have additionally established a collaboration with Dr. Oscar Vivas at the University of Washington in Seattle to determine how protein turnover is altered during aging-related neurodegeneration in mice, and which alterations are rescued by interventions that are protective against brain aging. Metabolic labeling of mice for this study has begun. Finally we have written a protocol for the first clinical study that comprehensively assesses protein turnover in humans in multiple tissues and ages. We anticipate IRB approval and initiation of the study in the coming year.

我们已经在Skyline蛋白质组学平台中开发软件工具的第一个目标取得了重大进展。我们已经与Skyline Core开发团队（西雅图华盛顿大学的Michael MacCoss和Brendan MacLean）合作，开发了一种软件工具，该工具现已在Skyline外部工具商店中可用。蛋白质组研究杂志上已经接受了描述这项工作的手稿。 为了达到我们的第二个目标，我们使用该工具进行了第一项小鼠研究，以确定在明尼苏达州罗切斯特市梅奥诊所的克里斯托弗·亚当斯（Christopher Adams）实验室合作期间，在肌肉萎缩期间以不同的速率移交了哪些蛋白质。在通过我们的周转工具对这些数据的分析中，我们已经确定了与年龄相关的骨骼肌萎缩有关的改变线粒体和肌原纤维蛋白的子集。此手稿正在准备。 我们还与西雅图华盛顿大学的Oscar Vivas博士建立了合作，以确定小鼠衰老相关的神经变性过程中如何改变蛋白质的转换，并通过保护脑老化的干预措施来挽救哪些改变。这项研究的小鼠代谢标记已经开始。 最后，我们为第一项临床研究编写了一项方案，该方案可以全面评估多种组织和年龄中人类的蛋白质周转。我们预计IRB的批准并在来年开始研究。