Explore the words cloud of the NEURO_NMD project. It provides you a very rough idea of what is the project "NEURO_NMD" about.
The following table provides information about the project.
KING'S COLLEGE LONDON
|Coordinator Country||United Kingdom [UK]|
|Total cost||183˙454 €|
|EC max contribution||183˙454 € (100%)|
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
|Duration (year-month-day)||from 2017-05-01 to 2019-12-04|
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|1||KING'S COLLEGE LONDON||UK (LONDON)||coordinator||183˙454.00|
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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