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NMJALS SIGNED

In vivo analysis of neuromuscular junction stability in zebrafish models of amyotrophic lateral sclerosis

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 NMJALS project word cloud

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

technically    plan    fluorescent    onset    relevance    super    lethal    zebrafish    mechanisms    equilibrium    analysing    protein    neuronal    unrelated    als    point    cell    understand    adhesion    patient    appear    contexts    excellent    seem    microscopy    model    sclerosis    molecular    modifications    causes    event    stability    fish    quantification    degeneration    regulatory    mutations    neuromuscular    computational    imaging    resolution    precise    lateral    neurodegenerative    amyotrophic    therapies    defects    preceding    destabilisation    dynamic    subtle    regardless    live    multidisciplinary    characterisation    characterise    counteract    unravel    neurons    biology    interesting    specificity    organisation    motor    detecting    combine    patients    quantitative    neuron    maintenance    vertebrate    death    identification    turnover    genes    clock    slow    therapeutic    cytoskeleton    constituting    stabilisation    junctions    proteins    disease    tools    largely    molecules    progression    genetic    starts    individuals    innovative    dynamics    nmj   

Project "NMJALS" data sheet

The following table provides information about the project.

Coordinator
INSTITUT CURIE 

Organization address
address: rue d'Ulm 26
city: PARIS
postcode: 75231
website: www.curie.fr

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 France [FR]
 Total cost 185˙076 €
 EC max contribution 185˙076 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-11-16   to  2017-11-15

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT CURIE FR (PARIS) coordinator 185˙076.00

Map

 Project objective

Amyotrophic lateral sclerosis (ALS) is a late onset, lethal neurodegenerative disease of motor neurons that affects about 2 in 100,000 individuals per year. Different genetic mutations have been described in patients, but the genes involved seem unrelated and the causes of the disease appear complex and are still largely not understood. Of relevance, the destabilisation of neuromuscular junctions (NMJ) may be an early event, preceding neuronal death, making them an interesting therapeutic target to slow down disease progression. The goal of the study is to characterise the molecular organisation and dynamics of NMJ, in particular of cell adhesion molecules, in order to understand the mechanisms of maintenance of NMJ by analysing defects in their organisation in ALS contexts. Technically, we plan to combine neuron biology, quantitative cell biology and computational tools to reach a precise molecular understanding of the dynamic equilibrium of NMJ in zebrafish, an excellent vertebrate model for live imaging. We will develop innovative methods of super-resolution microscopy and of quantification of protein turnover using a fluorescent molecular clock. This precise molecular characterisation of the NMJ will allow detecting subtle early changes in the NMJ that occur before neuronal degeneration starts, in fish carrying mutations described in ALS patients. The project will lead to the identification of key proteins for NMJ stabilisation and enable the analysis of regulatory elements of this stability, especially the cytoskeleton. The innovative multidisciplinary approach of this study will unravel early modifications in the organisation of the NMJ preceding neuronal degeneration in ALS contexts. It will point out key proteins of NMJ maintenance constituting new targets for the development of therapies to counteract destabilisation of neuromuscular junctions, regardless of the genetic specificity of the patient.

 Publications

year authors and title journal last update
List of publications.
2017 Shahad Albadri, Filippo Del Bene, Céline Revenu
Genome editing using CRISPR/Cas9-based knock-in approaches in zebrafish
published pages: 77-85, ISSN: 1046-2023, DOI: 10.1016/j.ymeth.2017.03.005
Methods 121-122 2019-06-18

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