Christoph Ziegenhain

Alternative splicing of pre-mRNA is a crucial regulator of cellular identities and gives rise to additional diversity in the human proteome. In this project, I will study the interplay of stochastic effects and deterministic regulation on outcomes of alternative splicing in human cells. Revealing novel insights into this poorly understood relationship will allow us to better comprehend the molecular mechanisms of this ubiquitous cellular process.Here, I will describe cell-to-cell variation in isoform choice at genome-wide resolution and resolve splicing patterns in single transcriptional bursts. In addition, I will shed light on the role of epigenetic cues governing alternative splicing control through new multimodal single-cell sequencing assays and complementary functional experiments. Lastly, using CRISPR/Cas9 screens I will generate a detailed splicing-regulatory network for RNA binding proteins in neuroprogenitors and in-vitro differentiated neurons at unprecedented resolution.This innovative research program is set at the intersection of cutting-edge experimental methodology and computational biology and will elucidate regulation of alternative splicing in an exciting and new direction. With new insights into splicing heterogeneity and its regulatory mechanisms, it may become possible to engineer more stable and effective regenerative medicine tools.