Core A. Metabolomics and lipidomics

核心A，摘要 这项技术核心，代谢组学和脂质组学核心，旨在提供系统级别的生化洞察 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)与疾病相关的压力源。要做到这一点，它将主要利用一套新陈代谢技术。 由这一核心开创，专门为研究结核分枝杆菌生理学而开发。尽管人们普遍认为 新陈代谢作为生物合成前体和能量的定量来源的重要性，越来越多的证据表明 确立了它作为几乎所有生理学的同等重要和特定的质量调节因子的重要性 流程。因此，代谢组学正在成为了解系统级生物化学的窗口。 该核心将专门提供生物无偏的代谢脂体读数：(I)体外活性 结核分枝杆菌(Mtb)适应的关键基因、蛋白质和非编码RNA 与疾病相关的应激源；以及(Ii)它们在野外的生理联系途径的身份和活动 类型和基因工程结核分枝杆菌菌株。核心的具体目标是：(1)解决体外生化 纯化的功能未知或仅类水平注释的重组Mtb蛋白的活性；(2)执行 野生型和转基因结核分枝杆菌菌株的无偏代谢脂组比较；以及(3)执行 结核分枝杆菌蛋白质组基于活性的代谢组学比较。

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.