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Breakborder SIGNED

Breaking borders, Functional genetic screens of structural regulatory DNA elements

Total Cost €

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EC-Contrib. €

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Partnership

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 Breakborder project word cloud

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

transcriptional    datasets    chromatin    genome    lacking    progress    architecture    opened    regions    structural    strategies    magnitude    survival    natural    showed    foundation    editing    crispr    nevertheless    human    regulation    strategy    resistance    proliferation    validate    setting    screening    cancer    scientific    mammalian    impeding    types    successful    scalability    outlined    sequencing    therapy    transcribed    expression    action    tools    screens    phenotypes    occurring    forms    carries    recruit    tumour    homeostasis    regulatory    structure    parallel    setup    distinguish    oncogenic    aberrations    altogether    underlying    induction    technologies    genes    rdes    postulated    interestingly    acquired    cell    genetic    extension    functional    3d    toolbox    understand    mechanisms    expanded    line    plan    suppressive    differentiation    insulators    examine    cellular    effectivity    decipher    enhancers    principles    dna    gene    indispensable    metastasis    players    transcription    organismal    insulate    pattern   

Project "Breakborder" data sheet

The following table provides information about the project.

Coordinator
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS 

Organization address
address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX
website: www.nki.nl

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 Netherlands [NL]
 Total cost 2˙497˙000 €
 EC max contribution 2˙497˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-ADG
 Funding Scheme ERC-ADG
 Starting year 2019
 Duration (year-month-day) from 2019-09-01   to  2024-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS NL (AMSTERDAM) coordinator 2˙497˙000.00

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 Project objective

The human genome carries genetic information in two distinct forms: Transcribed genes and regulatory DNA elements (rDEs). rDEs control the magnitude and pattern of gene expression, and are indispensable for organismal development and cellular homeostasis. Nevertheless, while large-scale functional genetic screens greatly advanced our knowledge in studying mammalian genes, such tools to study rDEs were lacking, impeding scientific progress. Interestingly, recent advance in genome editing technologies has not only expanded the available screening toolbox to examine genes, but also opened up novel opportunities in studying rDEs. We distinguish two types of rDEs: Transcriptional rDEs that recruit transcription factors to enhancers, and structural rDEs that maintain chromatin 3D structure to insulate transcriptional activities, a feature postulated to be essential for gene expression regulation by enhancers. Recently, we developed a CRISPR strategy to target enhancers. We showed its scalability and effectivity in identifying potential oncogenic and tumour-suppressive enhancers. Here, we will exploit this line of research and develop novel strategies to target structural rDEs (e.g. insulators). By setting up functional genetic screens, we will identify key players in cell proliferation, differentiation, and survival, which are related to cancer development, metastasis induction, and acquired therapy resistance. We will validate key insulators and decipher underlying mechanisms of action that control phenotypes. In a parallel approach, we will analyse whole genome sequencing datasets of cancer to identify and characterize genetic aberrations occurring in the identified regions. Altogether, the outlined research plan forms a natural extension of our successful functional approaches to study gene regulation. Our results will setup the foundation to better understand principles of chromatin architecture in gene expression regulation in development and cancer.

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

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