Core A. Metabolomics and lipidomics

核心 A. 代谢组学和脂质组学

• 批准号: 10426176
• 负责人: Kyu Y Rhee
• 金额: $ 24.47万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-12 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426176
• 关键词: Biochemical; Biochemical Reaction; Biochemistry; Bioinformatics; Biological Assay; Cells; Collaborations; Detection; Disease; Enzymes; Gene Proteins; Genes; Genetic Engineering; Goals; In Vitro; Individual; Link; Lipids; Mass Spectrum Analysis; Mediating; Mediator of activation protein; Metabolic; Metabolism; Methods; Molecular; Mycobacterium tuberculosis; Nucleic Acids; Nucleotides; Pathway Analysis; Pathway interactions; Physiological; Physiological Processes; Physiology; Proteins; Proteome; Proteomics; Publishing; Reagent; Recombinants; Research Project Grants; Resolution; Source; Structure-Activity Relationship; System; Technology; Tuberculosis; Untranslated RNA; base; computerized data processing; gene function; genetic manipulation; in vitro activity; insight; lipidome; lipidomics; metabolomics; protein profiling; protein structure function; small molecule; stressor; tool

Core A, Abstract This technology core, Metabolomics and Lipidomics Core, aims to provide systems level biochemical insight into the function of key genes, proteins and non-coding RNAs required for adaptation of Mycobacterium tuberculosis (Mtb) to disease relevant stressors. To do so, it will make use of a suite of metabolomic technologies largely pioneered by this core and specifically developed for studies of Mtb physiology. Despite the widely recognized importance of metabolism as a quantitative source of biosynthetic precursors and energy, growing evidence has established its importance as an equally important and specific qualitative mediator of nearly all physiologic processes. Metabolomics is thus emerging as a window into systems level biochemistry. This core will specifically provide biologically unbiased metabo-lipidomic readouts of: (i) the in vitro activities of key genes, proteins and non-coding RNAs required for adaptation of Mycobacterium tuberculosis (Mtb) to disease relevant stressors; and (ii) the identities and activities of their physiologically linked pathways in wild type and genetically engineered Mtb strains. The Core’s Specific Aims are to: (1) Resolve the in vitro biochemical activities of purified recombinant Mtb proteins of unknown function or only class-level annotation; (2) Perform unbiased metabo-lipidomic comparisons of wild type and genetically manipulated Mtb strains; and (3) Perform unbiased activity-based metabolomic comparisons of Mtb proteomes.

核心 A，摘要 该技术核心，代谢组学和脂质组学核心，旨在提供系统级生化洞察 结核分枝杆菌适应所需的关键基因、蛋白质和非编码RNA的功能 (Mtb) 来应对疾病相关的压力源。为此，它将主要利用一套代谢组学技术。 尽管得到了广泛认可，但由该核心开创并专门为 Mtb 生理学研究而开发。 越来越多的证据表明新陈代谢作为生物合成前体和能量的定量来源的重要性 确立了其作为几乎所有生理学的同等重要且特定的定性调节因素的重要性 因此，代谢组学正在成为系统级生物化学的窗口。 该核心将专门提供以下生物学上无偏差的代谢脂质组学读数：(i) 的体外活性 结核分枝杆菌 (Mtb) 适应所需的关键基因、蛋白质和非编码 RNA 疾病相关的应激源；以及（ii）其在野外的生理相关途径的特性和活动 核心的具体目标是：（1）解决体外生化问题。 功能未知或仅进行类水平注释的纯化重组 Mtb 蛋白的活性 (2) 执行； 野生型和基因操纵结核分枝杆菌菌株的无偏代谢脂质组学比较；以及 (3) 进行 Mtb 蛋白质组的基于活性的无偏见代谢组学比较。