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TransTempoFold SIGNED

A need for speed: mechanisms to coordinate protein synthesis and folding in metazoans

Total Cost €

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EC-Contrib. €

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Partnership

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 TransTempoFold project word cloud

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

shapes    vivo    intricate    lines    metazoan    lineages    centred    metazoans    abundance    tissues    quality    networks    speed    maintained    created    fold    detrimental    homeostasis    quantitate    unknown    specialized    proteome    multiscale    uncover    translation    reveal    aging    integrity    codon    model    patterns    normal    structure    individual    supply    vulnerable    modulate    differentiated    neuronal    damage    biogenesis    mechanism    systematic    ribosome    synthesis    diverse    sequence    dynamics    regulatory    mrna    begin    pluripotent    first    isogenic    imbalanced    modulating    diseases    stem    identity    cell    health    cells    tolerate    conserved    cardiac    interplay    rely    cellular    differentiation    regulators    proteins    dimensional    explore    profiling    hallmark    depletion    expression    function    dissect    human    types    proteomes    protein    evolutionarily    screens    powerful    trna    trnas    folding    conformation    progeny    misfolded    defects    pools   

Project "TransTempoFold" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: MUENCHEN
postcode: 80539
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 Germany [DE]
 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-2018-STG
 Funding Scheme ERC-STG
 Starting year 2019
 Duration (year-month-day) from 2019-01-01   to  2023-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) coordinator 1˙500˙000.00

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 Project objective

Proteins function only after folding into complex three-dimensional shapes. Loss of protein conformation is detrimental for cellular health, and a hallmark of aging and diverse human diseases. To ensure proteome integrity, cells rely on an intricate interplay between protein synthesis, folding, and quality control. Since proteins often begin to fold during mRNA translation, codon choice and tRNA supply can promote this process by modulating translation speed. How metazoans exploit this mechanism to ensure protein homeostasis over a wide range of cells and tissues, or why some cell types are more vulnerable to translation defects and proteome damage remains unknown. Here, I will define how tRNA pools and the regulatory networks for protein biogenesis and homeostasis are tailored to specialized proteomes in different cell types. I propose a multiscale systems approach centred around: i) stem cells and differentiated progeny lines as a powerful model system, and ii) a novel method to modulate cellular tRNA pools in vivo. Isogenic lines of a range of normal cellular states will be created through the differentiation of human pluripotent stem cells into neuronal and cardiac lineages. In these lineages, I will first quantitate tRNA expression and abundance, and dissect their impact on translation dynamics with ribosome profiling. Second, I will use systematic depletion of individual tRNAs to explore how different cell types respond to imbalanced tRNA pools, and define how mRNA sequence and protein structure patterns program protein folding. Third, I will use loss-of-function screens to uncover evolutionarily conserved regulators of proteome integrity as a function of cell identity. This project will define how diverse metazoan cell proteomes are established and maintained, and reveal why some cells tolerate misfolded proteins better than others.

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

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