Lysosomal Metabolomics and pH

溶酶体代谢组学和 pH

基本信息

批准号：
10583542
负责人：
Feng Li
金额：
$ 35.29万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583542
关键词：
Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Amino Acids Astrocytes Atlases Biology Biology of Aging Cells Collaborations Coupled Data Analyses Disease Disease Progression Environment Enzymes Foundations Functional disorder Genetic Genetic Transcription Genotype Goals High Pressure Liquid Chromatography Hippocampus Homeostasis Knowledge Lasers Libraries Link Longevity Lysosomes Mass Spectrum Analysis Measures Metabolic Metabolism Methods Modification Multiomic Data Mus Neurodegenerative Disorders Neuroglia Neurons Nuclear Organelles Organism Pathogenesis Pathologic Pathology Pathway interactions Phagocytes Photons Physiological Play Process Proteome Protocols documentation Quality Control Regulation Research Research Project Grants Resolution Resources Role Sampling Scanning Series Signal Transduction System Tauopathies Techniques Technology Time Wild Type Mouse amino acid metabolism cell growth data acquisition fluorescence lifetime imaging genetic manipulation healthy aging imaging platform in vivo monitoring innovation lysosomal proteins macromolecule mass spectrometer metabolome metabolomics mouse model nanoscope new technology synergism tau Proteins technology platform trafficking two-photon

项目摘要

Abstract Lysosomes are highly specialized and dynamic cellular organelles, which constitute an acidic environment in the cell and are metabolic active by receiving and degrading macromolecules from the secretory, endocytic, autophagic and phagocytic trafficking pathways. At the same time, lysosomes act as the signaling center of the cell, and the metabolic status of the lysosome actively regulates nuclear transcription to govern various cellular activities, such as cell growth, metabolism and quality control. Misregulation of lysosomal activity has been associated with aging and age-associated diseases, including Alzheimer’s disease (AD). The Lysosomal Metabolomics and pH Core (Core C) will support three Research Projects in this PPG proposal to assess changes in lysosomal pH and metabolic activity through harnessing the power of high-throughput, high accuracy Mass Spectrometry (MS)-based metabolomics and high-resolution fluorescence lifetime imaging microscopy (FLIM). We will 1) perform lysosome-specific metabolomic profiling in aging and tauopathy mouse models, 2) assess lysosomal pH changes using FLIM. In addition, Core C will carry both technological and conceptual innovations by developing new technological platforms and by creating the first-in-class Aging- and Tauopathy-associated Lysosomal atlas (ATLas) of the lysosomal proteome and metabolome for mouse cortex and hippocampus in collaboration with Core A and Core B. Together, these studies will advance our current knowledge regarding the association between lysosomal functions and aging and AD tauopathy and provide powerful techniques and valuable resources to the fields of lysosomal biology, aging biology, and AD pathology.

抽象的溶酶体是高度专业化和动态的细胞器，它构成了酸性环境细胞通过接收和降解来自分泌、内吞、同时，溶酶体充当自噬和吞噬细胞运输途径的信号中心。细胞内，溶酶体的代谢状态主动调节核转录，从而调控细胞的各种功能。细胞生长、代谢和质量控制等活动的失调。与衰老和年龄相关疾病有关，包括阿尔茨海默病（AD）。代谢组学和 pH 核心（核心 C）将支持本 PPG 提案中的三个研究项目，以评估通过利用高通量、高通量的力量改变溶酶体 pH 和代谢活性基于准确质谱 (MS) 的代谢组学和高分辨率荧光寿命成像我们将 1) 对衰老和 tau 蛋白病小鼠进行溶酶体特异性代谢组学分析。模型，2) 使用 FLIM 评估溶酶体 pH 变化此外，Core C 将同时携带技术和技术。通过开发新技术平台和创建一流的老龄化和小鼠皮质溶酶体蛋白质组和代谢组的 tau 蛋白病相关溶酶体图谱 (ATLas) 和海马体与核心 A 和核心 B 合作。这些研究将共同推进我们当前的研究关于溶酶体功能与衰老和 AD tau 蛋白病之间关系的知识，并提供溶酶体生物学、衰老生物学和 AD 领域的强大技术和宝贵资源病理。