Core A. Metabolomics and lipidomics

核心A，摘要 该技术核心，代谢组学和脂质组学核心，旨在提供系统水平的生化洞察， 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)疾病相关的压力源。为此，它将在很大程度上利用一套代谢组学技术 由这一核心开创，专门为结核病生理学研究而开发。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具体的定性介质的重要性。 流程.因此，代谢组学正在成为系统水平生物化学的窗口。 该核心将具体提供以下的生物学上无偏倚的代谢脂质组学读数：（i）以下的体外活性： 结核分枝杆菌（Mtb）适应 疾病相关的压力;和（ii）他们的生理联系途径的身份和活动，在野生 型和基因工程Mtb菌株。该核心的具体目标是：（1）解决体外生化 功能未知或仅类别水平注释的纯化的重组Mtb蛋白的活性;（2） 野生型和遗传操作的Mtb菌株的无偏代谢脂质组学比较;和（3）进行 Mtb蛋白质组的无偏活性代谢组学比较。

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.