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BioMeTRe SIGNED

Biophysical mechanisms of long-range transcriptional regulation

Total Cost €

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EC-Contrib. €

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Partnership

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 BioMeTRe project word cloud

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

interactions    mechanisms    levels    modeling    sequences    quantitative    topologically    promoters    cell    associating    fiber    relate    enzymatic    paradigms    boundaries    testable    transcriptional    confounding    data    details    enhancers    epigenetics    mutual    domains    molecular    structure    partitioned    formulate    biology    located    revealed    chromosomal    enhancer    smaller    tuned    structures    hundreds    gene    predictions    fine    genes    genetic    entirely    explore    sub    physical    description    promoter    chromosome    perturbations    showed    translate    models    principles    single    relies    linked    mammals    communication    chromatin    link    tads    regulatory    tad    experimental    megabase    dimensional    vivo    functional    conformation    engineering    distal    cis    mechanistic    chromosomes    cells    underlying    genomic    restrict    operation    regulation    transcription    totally    cognate    layer    interpret    unknown    time    biophysical    proximity    population    kilobases    tens    capture    away    preferential    experiments    outputs   

Project "BioMeTRe" data sheet

The following table provides information about the project.

Coordinator
FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION 

Organization address
address: MAULBEERSTRASSE 66
city: BASEL
postcode: 4058
website: www.fmi.ch

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 Switzerland [CH]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-01-01   to  2022-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION CH (BASEL) coordinator 1˙500˙000.00

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 Project objective

In mammals, transcriptional control of many genes relies on cis-regulatory elements such as enhancers, which are often located tens to hundreds of kilobases away from their cognate promoters. Functional interactions between distal regulatory elements and target promoters require mutual physical proximity, which is linked to the three-dimensional structure of the chromatin fiber. Chromosome conformation capture studies revealed that chromosomes are partitioned into Topologically Associating Domains (TADs), sub-megabase domains of preferential physical interactions of the chromatin fiber. Genetic evidence showed that TAD boundaries restrict the genomic range of enhancer-promoter communication, and that interactions between regulatory sequences within TADs are further fine-tuned by smaller-scale structures. However, the mechanistic details of how physical interactions translate into transcriptional outputs are totally unknown. Here we propose to explore the biophysical mechanisms that link chromosome conformation and long-range transcriptional regulation using molecular biology, genetic engineering, single-cell experiments and physical modeling. We will measure chromosomal interactions in single cells and in time using a novel method that relies on an enzymatic process in vivo. Genetic engineering will be used to establish a cell system that allows quantitative measurement of how enhancer-promoter interactions relate to transcription at the population and single-cell levels, and to test the effects of perturbations without confounding effects. Finally, we will develop physical models of promoter operation in the presence of distal enhancers, which will be used to interpret the experimental data and formulate new testable predictions. With this integrated approach we aim at providing an entirely new layer of description of the general principles underlying transcriptional control, which could establish new paradigms for research in epigenetics and gene regulation.

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

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