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NEURO_NMD SIGNED

Functional impact of alternative splicing coupled to nonsense-mediated decay in developing neurons

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 NEURO_NMD project word cloud

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

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Project "NEURO_NMD" data sheet

The following table provides information about the project.

Coordinator
KING'S COLLEGE LONDON 

Organization address
address: STRAND
city: LONDON
postcode: WC2R 2LS
website: www.kcl.ac.uk

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 United Kingdom [UK]
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-05-01   to  2019-12-04

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KING'S COLLEGE LONDON UK (LONDON) coordinator 183˙454.00

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 Project objective

Differentiation of precursor cells into mature neurons relies on transcriptome-wide changes in gene expression that have to be coordinated in a precise spatiotemporal fashion. Alternative pre-mRNA splicing coupled to nonsense-mediated decay (AS-NMD) is a widespread post-transcriptional mechanism known to orchestrate gene expression dynamics in developmental contexts. Earlier studies identified several neural targets of this pathway; however, in most cases, the extent to which AS-NMD contributes to the overall gene expression dynamics and biological significance of this regulation is poorly understood. Moreover, whether AS-NMD target repertoire undergoes considerable changes in developing brain and how this might fit to the global regulation network underlying neuronal differentiation remains unclear. I will address these questions using two separate approaches. First, I will investigate novel AS-NMD targets encoding actin cytoskeleton factors and controlled by an important regulator of neuronal alternative splicing, Ptbp1. I will elucidate the extent of AS-NMD regulation in these genes by modulating the inclusion of the NMD-promoting exons with corresponding antisense oligonucleotides. in mouse embryonic stem cells undergoing neuronal differentiation, neural stem cells and primary neurons. Second, I will systematically analyse how NMD contributes to different stages of neuronal development by acutely inhibiting this pathway in a time-resolved manner using genetic means. I will then identify gene expression effects and functional consequences of NMD inactivation using transcriptome sequencing (RNA-Seq) and appropriate cell biological methods. All in all, this work will provide critical quantitative insights into AS-NMD functions and uncover novel mechanisms allowing neurons to attain their unique morphological and functional properties.

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