Core B - Metabolomics

核心 B - 代谢组学

• 批准号: 9359469
• 负责人: ANDREI L OSTERMAN
• 金额: $ 8.08万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-22 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9359469
• 关键词: Amino Acids; Area; Asparagine; Aspartate; BRAF gene; Biochemical Pathway; Bioenergetics; Biogenesis; Biological Assay; Carbon; Cell Fraction; Cell Line; Cell Proliferation; Cellular Stress; Citric Acid Cycle; Collaborations; Complement; Cultured Cells; Data; Development; Diagnosis; Endoplasmic Reticulum; Ensure; Enzymatic Biochemistry; Enzymes; Follow-Up Studies; Funding; Future; Genus Hippocampus; Glucose; Glutamine; Glycolysis; Goals; Grant; High Pressure Liquid Chromatography; Homeostasis; Individual; Isotopes; Kinetics; Label; Link; Malignant - descriptor; Malignant Neoplasms; Mass Fragmentography; Measurement; Measures; Melanoma Cell; Metabolic; Metabolic Pathway; Metabolism; Methodology; Methods; Mission; Mitochondria; Modeling; Neoplasm Metastasis; Nucleic Acids; Nutrient; Oxygen Consumption; Pathway interactions; Phase; Process; Program Research Project Grants; Progress Reports; Proline; Property; Protein Analysis; Proteins; Protocols documentation; Publications; Publishing; Radioisotopes; Research Personnel; Research Project Grants; Resistance; Sampling; Stable Isotope Labeling; Starvation; Stratification; Sugar Acids; Techniques; Tissues; Work; amino acid metabolism; analytical method; base; cancer cell; cell type; comparative; deprivation; design; endoplasmic reticulum stress; enzyme analyzer; experience; experimental study; fatty acid metabolism; fatty acid oxidation; inhibitor/antagonist; instrument; melanoma; member; metabolic abnormality assessment; metabolic profile; metabolomics; novel strategies; preference; protein expression; receptor; response; screening; stable isotope; tumor; tumor metabolism; uptake

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.

总结-核心B：代谢 癌症的发展与细胞代谢的改变有内在联系。探讨这些 变化和基本的监管机制，目标是使新的方法， 黑色素瘤的诊断和治疗是P01项目的长期目标。主 核心B的总体目标是应用核心成员开发的代谢分析方法， 全面评估ER稳态改变和线粒体 在黑色素瘤中起作用，所有过程都与中央代谢密切相关。核心B将实现这一目标 通过独特的方法学组合，全面分析新陈代谢， 分析结果，以解释更广泛的代谢图片，和必要的经验，酶学详细 代谢酶的后续研究。中枢代谢已经是黑色素瘤研究的焦点， 在P01项目的第一阶段，研究人员与核心B领导人合作研究该基金。的 该核心的具体目标如下：（1）为所有三个提供全面的代谢分析支持 合作研究项目;（2）表征用于所有研究的细胞系的中心代谢 研究项目和核心C（黑色素瘤筛查和分层核心）;以及（3）为 通过协助酶和酶活性的表征来支持研究项目。中央方法 使用的是气相色谱-质谱（GC-MS）分析中的极性和非极性代谢物， 来源于用稳定同位素（13 C）标记的培养物的细胞或培养基的部分。GC-MS技术 产生关于代谢物数量的数据，并使用同位素示踪，关于代谢物来源和通过 代谢途径与其他测量底物摄取（YSI）和氧气的方法互补 消耗（海马），它提供了一个全面的评估中央代谢。一般而言，进一步 这种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 代谢和细胞代谢。