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BURSTREG SIGNED

Single-molecule visualization of transcription dynamics to understand regulatory mechanisms of transcriptional bursting and its effects on cellular fitness

Total Cost €

0

EC-Contrib. €

0

Partnership

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 BURSTREG project word cloud

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

inactivity    rate    ing    effect    orders    bursting    complexes    disease    behavior    contribution    influences    populations    transcriptional    promoter    site    synthesis    stability    arises    cis    depletion    though    observe    progression    imaging    dynamics    patterns    unknown    yeast    mutated    genes    endogenous    upstream    cells    output    interestingly    conserved    regulators    continuous    fashion    tuned    fate    rna    transcript    cell    fitness    first    techniques    cutting    switching    random    molecule    decisions    molecules    largely    noise    phenotypic    organism    collision    heterogeneity    gene    molecular    variability    noisiness    transcriptomes    examine    regulated    changing    time    bacteria    followed    reveal    origin    organismal    quantified    edge    single    trans    human    stochastic    living    dynamic    vary    binding    regulatory    periods    magnitude    proteins    observing    visualize    expression    transcription    transcribed   

Project "BURSTREG" 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]
 Project website https://www.nki.nl/divisions/gene-regulation/lenstra-t-group/
 Total cost 1˙950˙775 €
 EC max contribution 1˙950˙775 € (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    STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS NL (AMSTERDAM) coordinator 1˙950˙775.00

Map

 Project objective

Transcription in single cells is a stochastic process that arises from the random collision of molecules, resulting in heterogeneity in gene expression in cell populations. This heterogeneity in gene expression influences cell fate decisions and disease progression. Interestingly, gene expression variability is not the same for every gene: noise can vary by several orders of magnitude across transcriptomes. The reason for this transcript-specific behavior is that genes are not transcribed in a continuous fashion, but can show transcriptional bursting, with periods of gene activity followed by periods of inactivity. The noisiness of a gene can be tuned by changing the duration and the rate of switching between periods of activity and inactivity. Even though transcriptional bursting is conserved from bacteria to yeast to human cells, the origin and regulators of bursting remain largely unknown. Here, I will use cutting-edge single-molecule RNA imaging techniques to directly observe and measure transcriptional bursting in living yeast cells. First, bursting properties will be quantified at different endogenous and mutated genes to evaluate the contribution of cis-regulatory promoter elements on bursting. Second, the role of trans-regulatory complexes will be characterized by dynamic depletion or gene-specific targeting of transcription regulatory proteins and observing changes in RNA synthesis in real-time. Third, I will develop a new technology to visualize the binding dynamics of single transcription factor molecules at the transcription site, so that the stability of upstream regulatory factors and the RNA output can directly be compared in the same cell. Finally, I will examine the phenotypic effect of different bursting patterns on organismal fitness. Overall, these approaches will reveal how bursting is regulated at the molecular level and how different bursting patterns affect the heterogeneity and fitness of the organism.

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

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