Investigating the regulation of alternative splicing and its role in disease

细胞命运决定的RNA结合蛋白(RBPs)的鉴定。为了系统地识别限制性商业惯例在正常生理和疾病中的重要作用，我们将在一系列干细胞向神经元分化的过程中，将CHyMErA介导的限制性商业惯例的遗传扰动与单细胞中丰富的转录组读出相结合。此外，我们将通过组合靶向限制性商业惯例和阐明复杂的基因调控网络来扩展这些研究。为此，我们将利用CHyMErA的遗传相互作用作图能力，并设计一个针对数百个单独和组合的限制性商业惯例的文库。

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.