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EpigenomeProgramming SIGNED

An experimental and bioinformatic toolbox for functional epigenomics and its application to epigenetically making and breaking a cancer cell

Total Cost €

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EC-Contrib. €

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Partnership

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 EpigenomeProgramming project word cloud

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

copying    difficult    dissecting    recruitment    functionally    samples    creation    frequent    annotate    converting    co    comprising    leukemia    successful    programming    essentially    function    distinguish    assays    methodology    overcome    epigenetic    datasets    roles    editing    alterations    assisted    experiments    limitations    genetic    biological    vitro    carry    rescue    generate    cells    correlated    first    guide    ultimate    defects    knockout    rna    excellent    broadly    patient    collection    predictions    explore    human    modifiers    detected    applicable    rate    model    cancers    crispr    lack    disease    locus    data    cancer    strives    functional    purely    vice    epigenome    libraries    regulators    perturbation    breaking    summary    tools    validate    introducing    driver    toolbox    versa    profiles    statistically    ambition    drugs    prevalence    tend    mutation    events    cell    experimental    thousands    candidate    despite    bioinformatic   

Project "EpigenomeProgramming" 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]
 Project website https://cemm.at/research/funding/international-funding/erc-starting-grant-epigenomeprogramming/
 Total cost 1˙281˙205 €
 EC max contribution 1˙281˙205 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-12-01   to  2021-11-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH AT (WIEN) coordinator 1˙281˙205.00

Map

 Project objective

Epigenetic alterations can be detected in all cancers and in essentially every patient. Despite their prevalence, the concrete functional roles of these alterations are not well understood, for two reasons: First, cancer samples tend to carry many correlated epigenetic alterations, making it difficult to statistically distinguish relevant driver events from those that co-occur for other reasons. Second, we lack tools for targeted epigenome editing that could be used to validate biological function in perturbation and rescue experiments.

The proposed project strives to overcome these limitations through experimental and bioinformatic methods development, with the ambition of making and breaking cancer cells in vitro by introducing defined sets of epigenetic alterations. We will focus on leukemia as our “model cancer” (given its low mutation rate, frequent defects in epigenetic regulators, and availability of excellent functional assays), but the concepts and methods are general. In Aim 1, we will generate epigenome profiles for a human knockout cell collection comprising 100 epigenetic regulators and use the data to functionally annotate thousands of epigenetic alterations observed in large cancer datasets. In Aim 2, we will develop an experimental toolbox for epigenome programming using epigenetic drugs, CRISPR-assisted recruitment of epigenetic modifiers for locus-specific editing, and cell-derived guide RNA libraries for epigenome copying. Finally, in Aim 3 we will explore epigenome programming (methods from Aim 2) of candidate driver events (predictions from Aim 1) with the ultimate goal of converting cancer cells into non-cancer cells and vice versa.

In summary, this project will establish a broadly applicable methodology and toolbox for dissecting the functional roles of epigenetic alterations in cancer. Moreover, successful creation of a cancer that is driven purely by epigenetic alterations could challenge our understanding of cancer as a genetic disease.

 Publications

year authors and title journal last update
List of publications.
2020 André F. Rendeiro, Thomas Krausgruber, Nikolaus Fortelny, Fangwen Zhao, Thomas Penz, Matthias Farlik, Linda C. Schuster, Amelie Nemc, Szabolcs Tasnády, Marienn Réti, Zoltán Mátrai, Donát Alpár, Csaba Bödör, Christian Schmidl, Christoph Bock
Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-14081-6
Nature Communications 11/1 2020-02-05
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 2020-02-04
2019 Fabian Müller, Michael Scherer, Yassen Assenov, Pavlo Lutsik, Jörn Walter, Thomas Lengauer, Christoph Bock
RnBeads 2.0: comprehensive analysis of DNA methylation data
published pages: , ISSN: 1474-760X, DOI: 10.1186/s13059-019-1664-9
Genome Biology 20/1 2020-01-29
2019 Christian Schmidl, Gregory I. Vladimer, André F. Rendeiro, Susanne Schnabl, Thomas Krausgruber, Christina Taubert, Nikolaus Krall, Tea Pemovska, Mohammad Araghi, Berend Snijder, Rainer Hubmann, Anna Ringler, Kathrin Runggatscher, Dita Demirtas, Oscar Lopez de la Fuente, Martin Hilgarth, Cathrin Skrabs, Edit Porpaczy, Michaela Gruber, Gregor Hoermann, Stefan Kubicek, Philipp B. Staber, Medhat Sheh
Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL
published pages: 232-240, ISSN: 1552-4450, DOI: 10.1038/s41589-018-0205-2
Nature Chemical Biology 15/3 2020-01-29
2019 Florian Halbritter, Matthias Farlik, Raphaela Schwentner, Gunhild Jug, Nikolaus Fortelny, Thomas Schnoller, Hanja Pisa, Linda Christina Schuster, Andrea Reinprecht, Thomas Czech, Johannes Gojo, Wolfgang Holter, Milen Minkov, Wolfgang M Bauer, Ingrid Simonitsch-Klupp, Christoph Bock, Caroline Hutter
Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis
published pages: CD-19-0138, ISSN: 2159-8274, DOI: 10.1158/2159-8290.cd-19-0138
Cancer Discovery 2020-01-29
2017 Paul Datlinger, André F Rendeiro, Christian Schmidl, Thomas Krausgruber, Peter Traxler, Johanna Klughammer, Linda C Schuster, Amelie Kuchler, Donat Alpar, Christoph Bock
Pooled CRISPR screening with single-cell transcriptome readout
published pages: 297-301, ISSN: 1548-7091, DOI: 10.1038/nmeth.4177
Nature Methods 14/3 2020-01-29
2017 Heiko Müller, Raul Jimenez-Heredia, Ana Krolo, Tatjana Hirschmugl, Jasmin Dmytrus, Kaan Boztug, Christoph Bock
VCF.Filter: interactive prioritization of disease-linked genetic variants from sequencing data
published pages: W567-W572, ISSN: 0305-1048, DOI: 10.1093/nar/gkx425
Nucleic Acids Research 45/W1 2020-01-29
2018 Johanna Klughammer1,37, Barbara Kiesel2,3,37, Thomas Roetzer3,4, Nikolaus Fortelny1, Amelie Nemc1, Karl-Heinz Nenning5, Julia Furtner3,6, Nathan C. Sheffield7, Paul Datlinger1, Nadine Peter3,4, Martha Nowosielski8,9, Marco Augustin10, Mario Mischkulnig2,3, Thomas Ströbel3,4, Donat Alpar1, Bekir Ergüner1, Martin Senekowitsch1, Patrizia Moser11, Christian F. Freyschlag12, Johannes Kerschbaumer12, Claudius Thomé12, Astrid E. Grams13, Günther Stockhammer8, Melitta Kitzwoegerer14, Stefan Oberndorfer15, Franz Marhold16, Serge Weis17, Johannes Trenkler18, Johanna Buchroithner19, Josef Pichler20, Johannes Haybaeck21,22, Stefanie Krassnig21, Kariem M. Ali23, Gord von Campe23, Franz Payer24, Camillo Sherif25, Julius Preiser26, Thomas Hauser27, Peter A. Winkler27, Waltraud Kleindienst28, Franz Würtz29, Tanisa Brandner-Kokalj29, Martin Stultschnig30, Stefan Schweiger31, Karin Dieckmann3,32, Matthias Preusser3,33, Georg Langs6, Bernhard Baumann10, Engelbert Knosp2,3, Georg Widhalm2,3, Christine Marosi3,33, Johannes A. Hainfellner3,4, Adelheid Woehrer3,4,38* and Christoph Bock
The DNA methylation landscape of glioblastomadisease progression shows extensiveheterogeneity in time and space
published pages: , ISSN: 1078-8956, DOI: 10.1038/s41591-018-0156-x
Nature Medicine in press 2020-01-29
2018 Thomas F. Allison1,2, Peter W. Andrews 1, Yishai Avior3, Ivana Barbaric1, Nissim Benvenisty3, Christoph Bock 4,5,6, Jennifer Brehm7, Oliver Brüstle8, Ivan Damjanov 9, Andrew Elefanty10,11, Daniel Felkner7, Paul J. Gokhale1, Florian Halbritter 4, Lyn E. Healy12,13, Tim X. Hu 14, Barbara B. Knowles15,16, Jeanne F. Loring 17, Tenneille E. Ludwig7, Robyn Mayberry10,11, Suzanne Micallef10,11, Jameelah S. Mohamed14, Franz-Josef Müller 18,19, Christine L. Mummery20, Norio Nakatsuji21, Elizabeth S. Ng10,11, Steve K.W. Oh22, Orla O’Shea12, Martin F. Pera23,24,25,26,27, Benjamin Reubinoff28, Paul Robson 14,29,30, Janet Rossant 31,32, Bernhard M. Schuldt19, Davor Solter16,33, Koula Sourris10,11, Glyn Stacey12,34, Edouard G. Stanley10,11, Hirofumi Suemori35, Kazutoshi Takahashi36 & Shinya Yamanaka36,37
Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-04011-3
Nature Communications 9/1 2020-01-29
2018 Verhaak, Roel; Consortium, The Glioma
Glioma Through the Looking GLASS: the Glioma Longitudinal Analysis consortium, molecular evolution of diffuse gliomas
published pages: , ISSN: 1522-8517, DOI: 10.1101/196139
Neuro-Oncology 1 2020-01-29
2017 Nathan C Sheffield, Gaelle Pierron, Johanna Klughammer, Paul Datlinger, Andreas Schönegger, Michael Schuster, Johanna Hadler, Didier Surdez, Delphine Guillemot, Eve Lapouble, Paul Freneaux, Jacqueline Champigneulle, Raymonde Bouvier, Diana Walder, Ingeborg M Ambros, Caroline Hutter, Eva Sorz, Ana T Amaral, Enrique de Álava, Katharina Schallmoser, Dirk Strunk, Beate Rinner, Bernadette Liegl-Atzwanger, Berthold Huppertz, Andreas Leithner, Gonzague de Pinieux, Philippe Terrier, Valérie Laurence, Jean Michon, Ruth Ladenstein, Wolfgang Holter, Reinhard Windhager, Uta Dirksen, Peter F Ambros, Olivier Delattre, Heinrich Kovar, Christoph Bock, Eleni M Tomazou
DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma
published pages: 386-395, ISSN: 1078-8956, DOI: 10.1038/nm.4273
Nature Medicine 23/3 2020-01-29
2018 Boris Simovski, Chakravarthi Kanduri, Sveinung Gundersen, Dmytro Titov, Diana Domanska, Christoph Bock, Lara Bossini-Castillo, Maria Chikina, Alexander Favorov, Ryan M Layer, Andrey A Mironov, Aaron R Quinlan, Nathan C Sheffield, Gosia Trynka, Geir K Sandve
Coloc-stats: a unified web interface to perform colocalization analysis of genomic features
published pages: W186-W193, ISSN: 0305-1048, DOI: 10.1093/nar/gky474
Nucleic Acids Research 46/W1 2020-01-29
2018 Christian Baumgartner, Stefanie Toifl, Matthias Farlik, Florian Halbritter, Ruth Scheicher, Irmgard Fischer, Veronika Sexl, Christoph Bock, Manuela Baccarini
An ERK-Dependent Feedback Mechanism Prevents Hematopoietic Stem Cell Exhaustion
published pages: 879-892.e6, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.05.003
Cell Stem Cell 22/6 2020-01-29
2018 Chakravarthi Kanduri, Christoph Bock, Sveinung Gundersen, Eivind Hovig, Geir Kjetil Sandve
Colocalization analyses of genomic elements: approaches, recommendations and challenges
published pages: 1615-1624, ISSN: 1367-4803, DOI: 10.1093/bioinformatics/bty835
Bioinformatics 35/9 2020-01-29
2016 Matthias Farlik, Florian Halbritter, Fabian Müller, Fizzah A. Choudry, Peter Ebert, Johanna Klughammer, Samantha Farrow, Antonella Santoro, Valerio Ciaurro, Anthony Mathur, Rakesh Uppal, Hendrik G. Stunnenberg, Willem H. Ouwehand, Elisa Laurenti, Thomas Lengauer, Mattia Frontini, Christoph Bock
DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation
published pages: 808-822, ISSN: 1934-5909, DOI: 10.1016/j.stem.2016.10.019
Cell Stem Cell 19/6 2020-01-29
2018 Tahsin Stefan Barakat, Florian Halbritter, Man Zhang, André F. Rendeiro, Elena Perenthaler, Christoph Bock, Ian Chambers
Functional Dissection of the Enhancer Repertoire in Human Embryonic Stem Cells
published pages: 276-288.e8, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.06.014
Cell Stem Cell 23/2 2020-01-29

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