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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.

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

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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