Core B - Metabolomics

综述-核心B：代谢组学 癌症的发生与细胞新陈代谢的改变有着内在的联系。对这些问题的探索 变化和基本监管机制，目标是为 黑色素瘤的诊断和治疗，是P01计划项目的长期目标。初级阶段 核心B的总体目标是将核心成员开发的代谢概况方法应用于 内质网稳态和线粒体改变时代谢变化的综合评估 在黑色素瘤中发挥作用，所有这些过程都与中枢新陈代谢密切相关。核心B将实现这一目标 通过独特的方法组合全面分析新陈代谢，在口译方面的专业知识 分析结果解释了更广泛的代谢图景，并详细说明了所需的酶学经验 代谢酶的后续研究。中枢代谢已经是黑色素瘤研究的重点 在P01计划的第一阶段，这笔赠款的调查人员与核心B领导人合作。这个 这个核心的具体目标如下：(1)为所有三个人提供全面的代谢分析支持 合作研究项目；(2)表征ALL中使用的一组细胞系的中心代谢 研究项目和核心C(黑色素瘤筛查和分层核心)；以及(3)为 通过协助确定酶的特性和酶的活性来进行研究项目。中心方法 采用气相色谱-质谱法(GC-MS)分析黄曲霉中极性和非极性代谢物。 从用稳定同位素(13C)标记的培养物中提取的细胞或培养液的一部分。这项GC-MS技术 产生关于代谢物数量的数据，也使用同位素示踪，关于代谢物的来源和通过 代谢途径。与其他测量底物吸收(YSI)和氧气的方法相辅相成 消费(海马)，它提供了中央新陈代谢的全面评估。一般而言，进一步 这一新的代谢分析方法的进展也将为未来的癌症研究提供一个模型 新陈代谢和细胞新陈代谢。

SUMMARY – CORE B: METABOLOMICS The development of cancer is inherently linked to alterations in cellular metabolism. Exploration of these changes and the underlying regulatory mechanisms, with the goal of enabling new approaches for the diagnosis and treatment of melanoma, is a long-range objective of this P01 Program Project. The primary overall objective for Core B is to apply metabolic profiling methodology developed by core members for the comprehensive assessment of changes in metabolism upon altered ER homeostasis and mitochondrial function in melanoma, all processes that are tightly linked to central metabolism. Core B will fulfill this objective by a unique combination of methodology to comprehensively analyze metabolism, expertise in interpreting analytical results to explain the broader metabolic picture, and requisite experience in enzymology for detailed follow-up studies on metabolic enzymes. Central metabolism was already a focus for study in melanoma by the investigators of this grant in collaboration with the Core B leaders in the first phase of this P01 program. The Specific Aims of this core are as follows: (1) to provide comprehensive metabolic analytical support to all three collaborating research projects; (2) to characterize the central metabolism of the set of cell lines used in all research projects and Core C (melanoma screening and stratification core); and (3) to provide support to the research projects by assisting in the characterization of enzymes and enzymatic activities. The central method to be used is gas chromatography-mass spectrometry (GC-MS) analysis of polar and apolar metabolites in fractions of cells or medium derived from cultures labeled with stable isotopes (13C). This GC-MS technique yields data on metabolite quantities and also using isotope tracing, on metabolite origins and flux through metabolic pathways. Complemented with other methods to measure substrate uptake (YSI) and for oxygen consumption (Seahorse), it provides a comprehensive assessment of central metabolism. In general, further advances to this novel approach to metabolic analysis will also provide a model for future studies on cancer metabolism and cellular metabolism in general.