Project description DEENESFRITPL Following a stem cell on its journey to becoming a neuron The Human Genome Project identified all the genes present in the human genome, providing a list of building blocks that make us human. However, how those blocks are combined – which genes are expressed when and in which cells – is critical to identifying functions and it is particularly important during stem cell differentiation. The EU-funded SCAPA project plans to add its piece to the puzzle, shedding light on gene expression during differentiation of neuronal cells. Scientists are using high-tech methods to track a well-known pathway controlling gene expression, alternative polyadenylation, that can affect the availability of RNA binding sites. Analyses could point to molecular targets controlling gene expression during neuron development with exciting potential for new therapies. Show the project objective Hide the project objective Objective 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. Fields of science social sciencessociologydemographymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health scienceshealth sciencespersonalized medicinenatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysisnatural sciencesbiological sciencesgeneticsRNA Keywords single cell transcriptomics CRISPR screening Alternative Polyadenylation RNA binding proteins Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator FUNDACIO CENTRE DE REGULACIO GENOMICA Net EU contribution € 160 932,48 Address Carrer doctor aiguader 88 08003 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
