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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

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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.

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