Mitochondrial Parts, Pathways, and Pathogenesis

线粒体部分、途径和发病机制

• 批准号: 9492585
• 负责人: Vamsi Krishna Mootha
• 金额: $ 78.29万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-29 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9492585
• 关键词: Age; Aging; Applications Grants; Bayesian Analysis; Big Data; Biological; Biological Process; Catalogs; Cells; Childhood; Clustered Regularly Interspaced Short Palindromic Repeats; Computational algorithm; Defect; Degenerative Disorder; Disease; Emerging Technologies; Equipment and supply inventories; Foundations; Funding; Goals; Health; Human Genetics; Inborn Errors of Metabolism; Laboratories; Lead; Life; Link; Methods; Mitochondria; Mitochondrial Proteins; National Institute of General Medical Sciences; Organelles; Pathogenesis; Pathway interactions; Proteins; Proteome; Proteomics; Resolution; System; genome editing; human disease; metabolomics; new technology

Mitochondrial Parts, Pathways, and Pathogenesis ABSTRACT Mitochondria are ancient organelles central to eukaryotic life. Defects in these organelles underlie a spectrum of human diseases, ranging from rare inborn errors of metabolism to common age- associated degenerative diseases. The long-term goal of our laboratory is to achieve a systems- level understanding of this organelle that can serve as a foundation for studying mitochondria in health and in disease. NIGMS has provided the foundational funding for our laboratory which has enabled our ongoing efforts to systematically define the mitochondria's protein parts, organize them into functional pathways, and identify the proteins and pathways that underlie human disease. We have made tremendous progress, including producing MitoCarta, the most widely used catalog of mitochondrial protein parts. We have linked dozens of previously unstudied proteins to biological pathways and human diseases. However the protein inventory is not yet comprehensive and moreover contains hundreds of poorly studied proteins unlinked to any biological process in health or disease. In the next 5 years we aim to leverage emerging technologies in proteomics, Bayesian statistics, CRISPR, and high-resolution metabolomics, and human genetics to unveil the function of the dark corners of the mitochondrial proteome, while also pioneering new methods that can be generalized to other pathways within the cell.

线粒体部分，途径和发病机理 抽象的 线粒体是真核生物生活中心的古老细胞器。这些细胞器中的缺陷是 一系列人类疾病，范围从罕见的新陈代谢错误到普通年龄 相关的退行性疾病。我们实验室的长期目标是实现一个系统 - 对这个细胞器的水平理解可以作为研究线粒体的基础 健康和疾病。 Nigms为我们的实验室提供了基础资金 使我们能够系统地定义线粒体的蛋白质部件的持续努力，组织 它们进入功能途径，并识别人类构成的蛋白质和途径 疾病。我们取得了巨大的进步，包括生产Mitocarta，这是最广泛的 使用线粒体蛋白部分的目录。我们已经链接了数十个以前未研究的 生物途径和人类疾病的蛋白质。但是蛋白质库存尚未 全面且包含数百种研究较少的蛋白质，未链接到任何 健康或疾病的生物过程。在接下来的5年中，我们旨在利用新兴 蛋白质组学，贝叶斯统计，CRISPR和高分辨率代谢组学的技术以及 人类遗传学以揭示线粒体蛋白质组的黑暗角落的功能，同时也 开创性的新方法可以推广到单元内的其他途径。