Investigating the regulation of alternative splicing and its role in disease

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Identification of RNA-binding proteins (RBPs) underlying cell fate decisions. To systematically identify RBPs with important roles in normal physiology and disease, we will couple CHyMErA-mediated genetic perturbations of RBPs with phenotypically rich transcriptome profiling read-outs in single cells during a series of stem cell differentiation towards the neuronal lineage. Furthermore, we will extend these studies by combinatorially targeting RBPs and elucidating complex gene regulatory networks. Towards this, we will exploit CHyMErA genetic interaction mapping capabilities and design a library that will target several hundreds of RBPs individually and combinatorially.