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StressOME SIGNED

Defining and modulating the stress granule proteome as a therapeutic strategy in Amyotrophic Lateral Sclerosis

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 StressOME project word cloud

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

derive    sclerosis    recruitment    skin    90    aggregation    onset    disease    imaging    reporter    antibody    symptom    matched    first    form    sals    genes    tdp    sufficient    dynamics    concentration    die    local    almost    inclusions    hindered    disassembly    obvious    prevented    sporadic    granules    familial    microenvironment    technique    composition    pathogenesis    cause    candidate    constitute    stressome    stresses    generate    how    lines    thought    causes    misexpress    modulate    cure    models    10    involvement    als    binding    devastating    proteome    stress    recognition    proteins    rna    cells    patient    drosophila    biotinylation    lack    neurons    toxicity    lateral    me    cell    transient    assembly    expressing    controls    misexpressed    parallel    time    exhibit    inheritance    structures    43    intracellular    clear    compare    recruited    amyotrophic    healthy    effect    live    neurodegenerative    aggregate    fals    patients    protein    cellular    age    granule   

Project "StressOME" data sheet

The following table provides information about the project.

Coordinator
VIB VZW 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

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 Belgium [BE]
 Total cost 166˙320 €
 EC max contribution 166˙320 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-05-01   to  2021-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB VZW BE (ZWIJNAARDE - GENT) coordinator 166˙320.00

Map

 Project objective

How do you study a disease with no known cause? Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Patients typically die 3-5 years after symptom onset. There is no cure. Finding a cure is hindered by the lack of obvious causes: although 10% of patients show familial inheritance (fALS), 90% of patients exhibit a sporadic form of ALS with no known cause (sporadic ALS, sALS). Almost all ALS patients demonstrate intracellular inclusions of the RNA binding protein TDP-43. However, it is not clear what process allows TDP-43 to aggregate, especially in sALS. This will be the focus of the proposed StressOME project. TDP-43, and other ALS-associated proteins are recruited into stress granules, transient structures that form in response to cellular stresses. Stress granules are thought to constitute a microenvironment with a high local concentration of TDP-43, sufficient to allow its aggregation; however this is prevented in healthy neurons. Therefore, the composition of stress granules may be crucial in the pathogenesis of ALS.

To determine whether the dynamics of stress granule assembly and disassembly are different in patient cells, I will derive skin cells from fALS and sALS cases and compare them to age-matched controls. In parallel, I will use a new technique called ‘biotinylation by antibody recognition’ to define the stress granule proteome in sALS and fALS patient cells for the first time. This will allow me to identify candidate genes that modulate stress granule dynamics. I will generate stress granule reporter lines and misexpress candidate proteins, using live cell imaging to determine their effect on the dynamics of stress granules and the recruitment of TDP-43. Candidate genes will also be misexpressed in Drosophila models expressing TDP-43 in order to test their involvement in aggregation and toxicity. Through this approach I will identify novel targets that affect the aggregation of TDP-43 not only in fALS but also sALS.

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

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