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TRANSREG SIGNED

Dissecting the role of Translational Regulation in Tumorigenesis

Total Cost €

0

EC-Contrib. €

0

Partnership

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 TRANSREG project word cloud

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

stages    fundamentally    malignant    driving    cellular    frontier    downstream    eif2    relevance    constitute    initiation    drivers    revealed    tumor    unearthed    generate    gain    homeostasis    suggest    collectively    impose    fate    uorfs    malignancy    correlations    unveiled    upstream    transition    differentiation    tumorigenesis    elucidate    protein    monitor    systematically    tools    programs    unprecedented    expression    unravel    diagnostics    uorf    determinant    detect    treatment    crispr    defines    cas9    databases    cancer    reading    mice    regulators    oncogenic    networks    transformation    mrna    document    expose    unappreciated    analyze    intriguing    surprisingly    screen    force    surfacing    progression    conventional    mediated    function    levels    human    paradigms    conduct    observations    vivo    aberrant    raises    alternative    select    first    hitherto    translation    switch    gene    mechanistic    strategies    frame    eif2a    synthesis    turn    thousands    regulation    possibility    altered    translational    abundance   

Project "TRANSREG" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT ZURICH 

Organization address
address: RAMISTRASSE 71
city: ZURICH
postcode: 8006
website: n.a.

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˙977˙148 €
 EC max contribution 1˙977˙148 € (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 2018-08-01   to  2023-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT ZURICH CH (ZURICH) coordinator 1˙977˙148.00
2    UNIVERSITE DE LAUSANNE CH (LAUSANNE) participant 0.00

Map

 Project objective

The control of translation is a key determinant of protein abundance, which in turn defines cellular states. The impact of translational regulation may be even greater during the transition from homeostasis to malignancy, as revealed by the surprisingly low correlations between mRNA and protein levels in human cancer databases. This raises the intriguing possibility that through an ability to generate aberrant downstream networks of translational regulators, oncogenic drivers might impose altered protein synthesis programs that become the driving force for tumor formation and malignant progression. We recently unveiled a hitherto unappreciated role for upstream open reading frame (uORF) translation in tumorigenesis and unearthed a novel switch from conventional EIF2 initiation factor-mediated to alternative EIF2A-mediated uORF translation. These observations suggest that uORFs constitute an exciting new frontier in the field of translational regulation with the potential to fundamentally impact cellular fate. Here, I propose to systematically analyze the function of uORFs during tumorigenesis. First, we will conduct an in vivo CRISPR/CAS9-based screen in mice to elucidate the role of thousands of uORFs in development, differentiation and upon oncogenic transformation. Second, focusing on select uORFs surfacing in the screen, we will document their role during tumor initiation and progression. Third, we will develop novel tools to detect uORF translation in vivo, exploit them to monitor uORF translation during different stages of tumorigenesis, gain mechanistic insight into their function and finally test the relevance of these findings in human cancer. Collectively, these approaches will provide unprecedented and comprehensive insight into the function of uORFs, unravel new paradigms in the control of gene expression and expose novel strategies for cancer diagnostics and treatment.

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

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