Beyer, Andreas | Hänsel-Hertsch, Robert - C 02

Transcription by RNA Polymerase-II (Pol-II) is a highly controlled process. However, despite elaborate quality control mechanisms it is not error free. The fidelity of Pol-II declines with age resulting in increased elongation speed, increasing numbers of splicing mistakes and possibly increasing numbers of ‘transcriptional mistakes’, i.e. misincorporation of nucleotides in the mRNA molecule. In order to explore the physiological consequences for aging and disease we require new technologies that allow us to identify and quantify transcriptional mistakes. 

In this project we will develop methods for quantifying transcriptional mistakes based on single-cell RNA-sequencing protocols combined with newly developed bioinformatic methods. Our method will meet the technological challenge to distinguish transcriptional mistakes from technical errors during the sequencing process and DNA mutations. We are going to validate the method using single-cell data with known genomic variability. Subsequently, we will apply this technology to aging and age-associated disease models, including models of replicative senescence and the Hutchinson-Gilford progeria syndrome in order to study the emergence, origin and physiological consequences of transcriptional mistakes in vitro and in vivo.

For more information, please visit the following page: Beyer Lab.