Role of DNA PARylation in Epigenetic Gene Regulation
1 PhD project offered in the IPP summer call Molecular Mechanisms in Genome Stability & Gene Regulation
Scientific Background
Poly-ADP-ribosylation (PARylation) is a widespread post-translational modification of proteins. In mammalian cells, PARylation is regarded as protein-specific modification. However, we recently discovered that DNA in mammalian cells is PARylated. in mouse embryonic stem cells, mouse heart and muscle, brain, thymus, liver, placenta, and human liver. Furthermore, the modification is reversible by PAR glycohydrolases. We also discovered that DNA PARylation occurs on N1-deoxyadenosine, both in vitro and in vivo. Thus, N1-adenosine PARylation is a novel, reversible DNA modification in mammals (Musheev et al., 2022). This discovery raises many questions regarding the physiological role of DNA PARylation.
PhD project: Role of DNA PARylation in Epigenetic Gene Regulation
In this project, you will examine the role DNA PARylation in mouse embryonic stem cells (mESCs). You will generate and characterize PARylation-defective mutant mESCs by a variety of assays, including standard molecular biology, CRISPR Cas9 gene editing, confocal microscopy as well as Next-Generation-Sequencing. You will learn to analyze these Big Data by bioinformatic analysis. Thereby you will analyze epigenetic profiles in mESCs, to understand the molecular networks involved. You will also characterize PARylation-defective PARP enzymes involving recombinant protein expression and in vitro DNA Parylation.
You will work in a team of cell and molecular biologists and bioinformaticians. The successful candidate will have a strong background in Molecular-or Cell Biology.
If you are interested in this project, please select Niehrs as your group preference in the IPP application platform.
Publication relevant to the project
Musheev MU*, Schomacher L*, Basu A*, Han D, Krebs L, Scholz C and Niehrs C (2022) Mammalian N1-adenosine PARylation is a reversible DNA modification. Nat Commun, 13:6138 Link
