CancerFluxome SIGNED
Cancer Cellular Metabolism across Space and Time
Total Cost €
0EC-Contrib. €
0Partnership
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Explore the words cloud of the CancerFluxome project. It provides you a very rough idea of what is the project "CancerFluxome" about.
Project "CancerFluxome" data sheet
The following table provides information about the project.
| Coordinator |
TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Organization address contact info |
| Coordinator Country | Israel [IL] |
| Total cost | 1˙481˙250 € |
| EC max contribution | 1˙481˙250 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2016-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2017 |
| Duration (year-month-day) | from 2017-02-01 to 2022-01-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY | IL (HAIFA) | coordinator | 1˙481˙250.00 |
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Project objective
The metabolism of cancer cells is altered to meet cellular requirements for growth, providing novel means to selectively target tumorigenesis. While extensively studied, our current view of cancer cellular metabolism is fundamentally limited by lack of information on variability in metabolic activity between distinct subcellular compartments and cells.
We propose to develop a spatio-temporal fluxomics approach for quantifying metabolic fluxes in the cytoplasm vs. mitochondria as well as their cell-cycle dynamics, combining mass-spectrometry based isotope tracing with cell synchronization, rapid cellular fractionation, and computational metabolic network modelling.
Spatio-temporal fluxomics will be used to revisit and challenge our current understanding of central metabolism and its induced adaptation to oncogenic events – an important endeavour considering that mitochondrial bioenergetics and biosynthesis are required for tumorigenesis and accumulating evidences for metabolic alterations throughout the cell-cycle.
Our preliminary results show intriguing oscillations between oxidative and reductive TCA cycle flux throughout the cell-cycle. We will explore the extent to which cells adapt their metabolism to fulfil the changing energetic and anabolic demands throughout the cell-cycle, how metabolic oscillations are regulated, and their benefit to cells in terms of thermodynamic efficiency. Spatial flux analysis will be instrumental for investigating glutaminolysis - a ‘hallmark’ metabolic adaptation in cancer involving shuttling of metabolic intermediates and cofactors between mitochondria and cytoplasm.
On a clinical front, our spatio-temporal fluxomics analysis will enable to disentangle oncogene-induced flux alterations, having an important tumorigenic role, from artefacts originating from population averaging. A comprehensive view of how cells adapt their metabolism due to oncogenic mutations will reveal novel targets for anti-cancer drugs.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Shoval Lagziel, Won Dong Lee, Tomer Shlomi Studying metabolic flux adaptations in cancer through integrated experimental-computational approaches published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-019-0669-x |
BMC Biology 17/1 | 2020-03-05 |
| 2017 |
Eunyong Ahn, Praveen Kumar, Dzmitry Mukha, Amit Tzur, Tomer Shlomi Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle published pages: 953, ISSN: 1744-4292, DOI: 10.15252/msb.20177763 |
Molecular Systems Biology 13/11 | 2019-06-13 |
| 2019 |
Shoval Lagziel, Won Dong Lee, Tomer Shlomi Inferring cancer dependencies on metabolic genes from large-scale genetic screens published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-019-0654-4 |
BMC Biology 17/1 | 2019-06-06 |
| 2019 |
Won Dong Lee, Dzmitry Mukha, Elina Aizenshtein, Tomer Shlomi Spatial-fluxomics provides a subcellular-compartmentalized view of reductive glutamine metabolism in cancer cells published pages: 1351, ISSN: 2041-1723, DOI: 10.1038/s41467-019-09352-1 |
Nature Communications 10/1 | 2019-06-06 |
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