Investigating the regulation of alternative splicing and its role in disease

RNA结合蛋白（RBP）的鉴定是细胞命运决定的基础。为了系统地鉴定在正常生理学和疾病中具有重要作用的RBP，我们将在一系列干细胞向神经元谱系分化期间，将CHyMErA介导的RBP遗传扰动与单细胞中表型丰富的转录组分析读数偶联。此外，我们将通过组合靶向RBP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基因相互作用作图能力，并设计一个库，将单独和组合靶向数百个RBP。

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.