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TransTempoFold SIGNED

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

Total Cost €


EC-Contrib. €






 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.

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

Project "TransTempoFold" data sheet

The following table provides information about the project.


Organization address
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


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 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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