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CancerFluxome SIGNED

Cancer Cellular Metabolism across Space and Time

Total Cost €

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EC-Contrib. €

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Partnership

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 CancerFluxome project word cloud

Explore the words cloud of the CancerFluxome project. It provides you a very rough idea of what is the project "CancerFluxome" about.

hallmark    explore    efficiency    computational    disentangle    bioenergetics    revisit    cytoplasm    thermodynamic    biosynthesis    anti    mitochondria    fulfil    events    synchronization    intriguing    view    mutations    meet    changing    cycle    demands    preliminary    intermediates    shuttling    tumorigenesis    flux    clinical    quantifying    tracing    evidences    cofactors    glutaminolysis    selectively    isotope    fluxomics    regulated    drugs    dynamics    endeavour    front    adapt    metabolic    spatial    compartments    variability    central    mitochondrial    energetic    tca    lack    oscillations    network    cellular    population    altered    spatio    oxidative    cancer    reveal    spectrometry    cells    limited    considering    accumulating    alterations    benefit    reductive    artefacts    extensively    tumorigenic    vs    cell    metabolism    averaging    subcellular    rapid    oncogenic    anabolic    instrumental    fractionation    combining    originating    mass    fluxes    temporal    fundamentally    oncogene   

Project "CancerFluxome" data sheet

The following table provides information about the project.

Coordinator
TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY 

Organization address
address: SENATE BUILDING TECHNION CITY
city: HAIFA
postcode: 32000
website: www.technion.ac.il

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
1    TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY IL (HAIFA) coordinator 1˙481˙250.00

Map

 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
List of publications.
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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