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ConflictResolution SIGNED

Transcription-replication conflicts in disease and development

Total Cost €

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EC-Contrib. €

0

Partnership

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 ConflictResolution project word cloud

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

disease    mouse    breast    uncovering    zygotic    single    trigger    genomes    molecularly    expression    cancers    proximity    suitable    collision    genes    genome    cell    episomal    activation    innovative    pioneered    machineries    relevance    first    resolve    molecular    labelling    prevent    understudied    genetic    replication    apex2    pathological    owing    source    conflicts    split    tractable    differ    rewire    normal    question    collisions    local    instability    dna    cells    largely    mechanism    inducible    networks    arises    embryonic    indicate    unfortunately    paradigm    types    cellular    induce    potent    physical    gene    cutting    edge    sites    disorders    epigenetic    neurological    localized    developmental    principles    cancer    map    endogenous    chromatin    fashion    decipher    shift    link    data    model    epi    preliminary    lack    hypothesize    reprogram    diseases    aging    millions    start    transformations    transcription    gap    human   

Project "ConflictResolution" data sheet

The following table provides information about the project.

Coordinator
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH 

Organization address
address: INGOLSTADTER LANDSTRASSE 1
city: NEUHERBERG
postcode: 85764
website: www.helmholtz-muenchen.de

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 Germany [DE]
 Total cost 1˙497˙530 €
 EC max contribution 1˙497˙530 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-02-01   to  2025-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH DE (NEUHERBERG) coordinator 1˙497˙530.00

Map

 Project objective

Genetic and epigenetic instability contribute to cancers, aging, developmental disorders, and neurological diseases, so in-depth understanding how this instability arises is an important question affecting millions in Europe. Physical conflicts between the transcription and DNA replication machineries are a potent endogenous source of this instability. My preliminary data indicate that a single collision can trigger long-term epigenetic changes and affect the normal expression state of genes. I hypothesize that collisions can rewire gene expression networks and lead to cellular transformations relevant to disease and development. Unfortunately, this mechanism is largely understudied owing to the lack of suitable cellular systems to characterize collisions in molecular detail. My proposal will address this key gap in knowledge. I recently pioneered a unique human cell-based episomal system to analyse collisions in an inducible and localized fashion. Using this highly tractable system, we will molecularly characterize the (epi)genetic consequences and identify novel factors that prevent or resolve collisions (Aim 1). To address the relevance of collisions in disease, we will establish a novel proximity-labelling system (Split-APEX2) to map collision sites and identify their associated genetic and chromatin changes in a breast cancer cell model. This cutting-edge technology will decipher their role in pathological transformations observed in breast cancer genomes (Aim 2). To link collisions to developmental transformations, we will determine their potential to induce local epigenetic changes during zygotic genome activation in mouse embryonic cells. This approach can shift the paradigm how cells in development first start to differ from each other and reprogram their genome into different cell types (Aim 3). Uncovering the key principles of collisions may implement highly innovative approaches to avoid or establish cellular transformations in disease and development.

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