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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.

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

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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