SCAPA | Functional analysis of Alternative Polyadenylation during neuronal differentiation at single cell resolution

Summary
Understanding how stem cells differentiate into the myriad of cell types that compose an organism is a fundamental question in biomedical sciences. The recent development of single-cell transcriptomic techniques has already allowed the study of the cell composition of organs and tissues, developmental stages, and even whole adult organisms. Yet, in most cases, these studies are primarily descriptive and often provide little insight into the mechanisms regulating gene expression during cell differentiation.
Here, I propose to study the role of alternative polyadenylation (APA) and associated RNA binding proteins (RBPs) in neuronal differentiation. For this purpose, I will: (i) develop new computational tools to detect and quantify APA events from single-cell transcriptomics data; and (ii) perform a single-cell-based functional CRISPR screen. The results obtained from this study will provide an in depth analysis of the changes in gene expression and APA during neuronal differentiation at a single cell resolution and identify dozens of APA targets specifically associated with individual RBPs.
Together, this study will provide a solid molecular knowledge of the role of APA in neural differentiation, enabling the development of new personalized medicine therapies, which is in compliance with the Horizon H2020 Health demographic change and wellbeing programme.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/840252
Start date: 01-04-2019
End date: 31-03-2021
Total budget - Public funding: 160 932,48 Euro - 160 932,00 Euro
Cordis data

Original description

Understanding how stem cells differentiate into the myriad of cell types that compose an organism is a fundamental question in biomedical sciences. The recent development of single-cell transcriptomic techniques has already allowed the study of the cell composition of organs and tissues, developmental stages, and even whole adult organisms. Yet, in most cases, these studies are primarily descriptive and often provide little insight into the mechanisms regulating gene expression during cell differentiation.
Here, I propose to study the role of alternative polyadenylation (APA) and associated RNA binding proteins (RBPs) in neuronal differentiation. For this purpose, I will: (i) develop new computational tools to detect and quantify APA events from single-cell transcriptomics data; and (ii) perform a single-cell-based functional CRISPR screen. The results obtained from this study will provide an in depth analysis of the changes in gene expression and APA during neuronal differentiation at a single cell resolution and identify dozens of APA targets specifically associated with individual RBPs.
Together, this study will provide a solid molecular knowledge of the role of APA in neural differentiation, enabling the development of new personalized medicine therapies, which is in compliance with the Horizon H2020 Health demographic change and wellbeing programme.

Status

TERMINATED

Call topic

MSCA-IF-2018

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2018
MSCA-IF-2018