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NUAGE SIGNED

Nucleolar regulation of longevity

Total Cost €

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EC-Contrib. €

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Partnership

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 NUAGE project word cloud

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

uncover    clarify    survey    fib    mechanism    malleable    function    signals    methylase    proteomic    species    animals    ncl    decades    restriction    illuminate    nucleolus    knockout    elusive    stress    molecular    mtor    furzeri    metabolic    immunity    regulating    recognition    life    pathogen    size    revealed    transcriptomic    igf    biomarkers    animal    organelle    controls    remained    enhances    trim2    global    regulate    elegans    focal    renders    responds    fibrillarin    candidate    rna    nucleoli    action    small    mitochondrial    diverse    interacting    few    innate    levels    point    complexes    spliceosomes    ribonucleoprotein    killifish    regulators    expands    suppresses    nucleolargenesis    health    probe    genetic    ribogenesis    converge    extension    extends    particle    reduces    screens    perform    span    research    found    subnuclear    humans    signaling    knockdown    discovered    hallmark    conserved    cellular    conversely    last    granules    correlate    signal    longevity    molecules    remarkably    assembly    rrna    ribosomal    insulin    groundbreaking    reproductive    dietary    nucleolar    lived    revealing    notobranchius    regulation    sensitive    regulated   

Project "NUAGE" 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 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-ADG
 Funding Scheme ERC-ADG
 Starting year 2020
 Duration (year-month-day) from 2020-01-01   to  2024-12-31

 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 2˙500˙000.00

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 Project objective

Research over the last few decades has revealed that animal life span is malleable and regulated by conserved metabolic signaling pathways, including reduced insulin/IGF signaling, mTOR, mitochondrial function, dietary restriction, and signals from the reproductive system. Whether these various pathways converge on common processes, however, has remained elusive.

We recently discovered the nucleolus to be a crucial focal point of regulation in all these pathways. The nucleolus is a subnuclear organelle dedicated to rRNA production and ribogenesis, but also controls assembly of other ribonucleoprotein complexes including spliceosomes, signal recognition particle, small RNA processing, stress granules, and responds to growth and stress signaling. Remarkably we found that small nucleoli are a cellular hallmark of longevity in diverse species, and a correlate of metabolic health in humans. At the molecular level, long-lived animals show reduced levels of the nucleolar ribosomal RNA methylase, fibrillarin (FIB-1), and knockdown of C. elegans FIB-1 reduces nucleolar size, extends life span, and enhances innate immunity. Conversely, knockout of NCL-1/TRIM2 expands nucleolar size, suppresses life extension of major longevity pathways, and renders animals pathogen sensitive, revealing key regulators of nucleolargenesis, immunity and longevity.

Here I propose to (Aim 1) clarify the mechanism of action of NCL-1, FIB-1 and interacting molecules (2) perform novel genetic screens for nucleolargenesis in C. elegans (3) uncover global transcriptomic and proteomic changes induced by NCL-1 and FIB-1 and survey several candidate nucleolar processes in regulating longevity and immunity (4) probe NCL-1/TRIM2 regulation of longevity in the short-lived killifish, Notobranchius furzeri, and develop nucleolar biomarkers of metabolic health in humans. These groundbreaking studies should illuminate how conserved signaling pathways work through the nucleolus to regulate health and life span.

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

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