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CHROMABOLISM SIGNED

Chromatin-localized central metabolism regulating gene expression and cell identity

Total Cost €

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EC-Contrib. €

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Partnership

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 CHROMABOLISM project word cloud

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

small    epigenetics    lack    posttranslational    forcing    cell    successful    exploited    modifications    clinical    molecules    enzymes    chart    export    metabolism    first    localization    protein    model    assumption    proliferation    central    nucleus    contrast    rnas    structure    discovery    concentrations    subnuclear    biomolecules    perturb    chromabolism    transform    regulation    preliminary    enter    hypothesize    expression    metabolomes    metabolites    generally    metabolite    local    cancer    profile    chemical    druggable    lines    bound    loci    depletion    dna    chromatin    final    validate    line    territories    leukemia    cytoplasm    representative    metabolic    patterns    cellular    occupy    recruiting    hypothesis    passively    compartmentalized    nuclear    revealed    systematically    oncology    oncometabolites    completion    probes    gradients    genomic    laboratory    tools    gene    aberrantly    thereby    kinds    perturbing    antimetabolites    proteins    data    identity    predict   

Project "CHROMABOLISM" data sheet

The following table provides information about the project.

Coordinator
CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH 

Organization address
address: LAZARETTGASSE 14 AKH BT 25.3
city: WIEN
postcode: 1090
website: http://www.oeaw.ac.at/

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 Austria [AT]
 Total cost 1˙980˙916 €
 EC max contribution 1˙980˙916 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-05-01   to  2023-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH AT (WIEN) coordinator 1˙980˙916.00

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 Project objective

Epigenetics research has revealed that in the cell’s nucleus all kinds of biomolecules–DNA, RNAs, proteins, protein posttranslational modifications–are highly compartmentalized to occupy distinct chromatin territories and genomic loci, thereby contributing to gene regulation and cell identity. In contrast, small molecules and cellular metabolites are generally considered to passively enter the nucleus from the cytoplasm and to lack distinct subnuclear localization. The CHROMABOLISM proposal challenges this assumption based on preliminary data generated in my laboratory. I hypothesize that chromatin-bound enzymes of central metabolism and subnuclear metabolite gradients contribute to gene regulation and cellular identity. To address this hypothesis, we will first systematically profile chromatin-bound metabolic enzymes, chart nuclear metabolomes across representative leukemia cell lines, and develop tools to measure local metabolite concentrations at distinct genomic loci. In a second step, we will then develop and apply technology to perturb these nuclear metabolite patterns by forcing the export of metabolic enzymes for the nucleus, aberrantly recruiting these enzymes to selected genomic loci, and perturbing metabolite patterns by addition and depletion of metabolites. In all these conditions we will measure the impact of nuclear metabolism on chromatin structure and gene expression. Based on the data obtained, we will model for the effects of cellular metabolites on cancer cell identity and proliferation. In line with the recent discovery of oncometabolites and the clinical use of antimetabolites, we expect to predict chromatin-bound metabolic enzymes that can be exploited as druggable targets in oncology. In a final aim we will validate these targets in leukemia and develop chemical probes against them. Successful completion of this project has the potential to transform our understanding of nuclear metabolism in control of gene expression and cellular identity.

 Publications

year authors and title journal last update
List of publications.
2019 Sara Sdelci, André F. Rendeiro, Philipp Rathert, Wanhui You, Jung-Ming G. Lin, Anna Ringler, Gerald Hofstätter, Herwig P. Moll, Bettina Gürtl, Matthias Farlik, Sandra Schick, Freya Klepsch, Matthew Oldach, Pisanu Buphamalai, Fiorella Schischlik, Peter Májek, Katja Parapatics, Christian Schmidl, Michael Schuster, Thomas Penz, Dennis L. Buckley, Otto Hudecz, Richard Imre, Shuang-Yan Wang, Hans M
MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation
published pages: 990-998, ISSN: 1061-4036, DOI: 10.1038/s41588-019-0413-z
Nature Genetics 51/6 2020-01-29
2019 Sandra Schick, André F. Rendeiro, Kathrin Runggatscher, Anna Ringler, Bernd Boidol, Melanie Hinkel, Peter Májek, Loan Vulliard, Thomas Penz, Katja Parapatics, Christian Schmidl, Jörg Menche, Guido Boehmelt, Mark Petronczki, André C. Müller, Christoph Bock, Stefan Kubicek
Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers
published pages: 1399-1410, ISSN: 1061-4036, DOI: 10.1038/s41588-019-0477-9
Nature Genetics 51/9 2020-01-29

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The information about "CHROMABOLISM" are provided by the European Opendata Portal: CORDIS opendata.

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