Metabolism in Action: Quantitative Fluxes in Mammals

新陈代谢在行动:哺乳动物的数量通量

基本信息

  • 批准号:
    9535989
  • 负责人:
  • 金额:
    $ 113.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-30 至 2021-07-31
  • 项目状态:
    已结题

项目摘要

Metabolism in Action: Quantitative Fluxes in Mammals Abstract The molecular connections involved in metabolism are the best understood of any major biochemical network. Nevertheless, metabolic disease remains at epidemic levels, and other diseases involving aberrant metabolism, such as cancer, continue unabated. A key step towards addressing these major unmet medical needs is to understand the integrated activity of metabolic pathways, and their modulation by diet and disease. Despite the recent revitalized interest in metabolism, systems-level methods for measuring metabolic activity in intact mammals remain in their infancy.Here I propose to combine isotope tracing, state-of-the-art metabolomics technology, and computational modeling to reveal metabolic activity at the whole body level. Labeled nutrients will be infused intravenously into mice, tissues sampled, and metabolite labeling quantified by liquid chromatography-mass spectrometry. Metabolic pathway flows (fluxes) consistent with the tracer data will be identified within the context of whole body metabolic model, which encompasses tissue-specific metabolic activity and exchange of metabolites between organs via the circulation. The fluxes will also be constrained by macroscopic measurements like food and oxygen uptake and carbon dioxide and urea excretion rates, tying our approach to classical physiological measurements. Through these studies, we will revisit from a quantitative perspective the overall operation of mammalian metabolism. Anticipated outcomes include enhanced understanding of the sources and consumption routes of circulating metabolites, discovery of novel metabolic cycles connecting different organs, and quantitative measurement methods of broad utility for probing disease models. Application of these methods will reveal disease-specific pathway dysregulation. The overall impact will be a more holistic and comprehensive understanding of metabolism that enables rational dietary guidance and therapeutic intervention across a broad spectrum of diseases.
作用中的代谢:哺乳动物的定量通量

项目成果

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JOSHUA D RABINOWITZ其他文献

JOSHUA D RABINOWITZ的其他文献

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{{ truncateString('JOSHUA D RABINOWITZ', 18)}}的其他基金

Mechanisms and consequences of metabolic manipulation by human cytomegalovirus
人类巨细胞病毒代谢操纵的机制和后果
  • 批准号:
    8532816
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Tumor Cell Dependence on Host Metabolism
肿瘤细胞对宿主代谢的依赖性
  • 批准号:
    9333585
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Mechanisms and consequences of metabolic manipulation by human cytomegalovirus
人类巨细胞病毒代谢操纵的机制和后果
  • 批准号:
    8697006
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Mechanisms and consequences of metabolic manipulation by human cytomegalovirus
人类巨细胞病毒代谢操纵的机制和后果
  • 批准号:
    8343995
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Identification of Metabolic Vulnerabilities of Ras-Driven Cancer Cells
Ras 驱动的癌细胞代谢脆弱性的鉴定
  • 批准号:
    8686780
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Identification of Metabolic Vulnerabilities of Ras-Driven Cancer Cells
Ras 驱动的癌细胞代谢脆弱性的鉴定
  • 批准号:
    8370625
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Tumor Cell Dependence on Host Metabolism
肿瘤细胞对宿主代谢的依赖性
  • 批准号:
    10192670
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Identification of Metabolic Vulnerabilities of Ras-Driven Cancer Cells
Ras 驱动的癌细胞代谢脆弱性的鉴定
  • 批准号:
    8525354
  • 财政年份:
    2012
  • 资助金额:
    $ 113.4万
  • 项目类别:
Mass Spectrometry Methods for Probing Metabolic Dynamics in Normal & Cancer Cells
探测正常代谢动态的质谱方法
  • 批准号:
    7432649
  • 财政年份:
    2008
  • 资助金额:
    $ 113.4万
  • 项目类别:
Mass Spectrometry Methods for Probing Metabolic Dynamics in Normal & Cancer Cells
探测正常代谢动态的质谱方法
  • 批准号:
    7615679
  • 财政年份:
    2008
  • 资助金额:
    $ 113.4万
  • 项目类别:

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