Epigenetic CRISPR approaches for the multi-layered analysis of gene activity regulating neural stem cell identity

• Applicant: Professor Dr. Stefan Stricker
• Subject Area: General Genetics and Functional Genome Biology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465820446

Despite the multitude of gene-regulatory mechanisms that have been described on the genetic, the epigenetic and the chromatin level, we still lack an understanding, how critical each of these individual mechanisms are for gene expression, and how they interact. The main reason for this is that those were never manipulated locally (1), side-by-side (2) using similar methodology (3) on an endogenous and critical gene (4). Since, one of the most important regulatory tasks of the cell is the control of cell identity factors, we propose the use of new experimental approaches based on the bacterial CRIPSR system, epigenome editing and screening to analyze mechanisms causally involved in the transcriptional regulation of the reprogramming transcription factor Sox1. Sox1 expression does not only differentiate neural stem cells from neural progenitor cells (NPCs) lacking the ability to produce neurons, Sox1 expression is also sufficient to restore neurogenic potency in these cells. By employing NPCs as a cellular and innovative CRISPR technologies as an experimental model system we aim to generate a multi-layered network map of gene regulation, by simultaneous discovery and characterization of genes, gene-regulatory elements and epigenetic features functionally regulating neural stem cell identity.

• DFG Programme: Research Grants