1 PhD project offered in the IPP winter call Molecular Mechanisms in Genome Stability & Gene Regulation

Scientific Background

Nucleic acid modifications, such as cytosine methylation and its oxidized derivatives (e.g., 5-formylcytosine [5fC]), play essential roles in gene regulation and epigenetic programming. These modifications can affect DNA structure, gene expression, and genome stability. Cytosine methylation (5mC) has been extensively studied, but less is known about the biological roles of its oxidized forms, including 5fC, which is implicated in active DNA demethylation (Parasyraki et al., 2024). Similarly, Adenosine PARylation represents a newly recognized DNA modification that involves the addition of poly-ADP-ribose (PAR) to adenosine residues, which we discovered (Musheev et al., 2022). This reversible process may be crucial for regulating DNA repair, replication, and transcription, further underscoring the importance of understanding these epigenetic mechanisms.

The integration of diverse DNA sequencing technologies has opened exciting avenues for studying nucleic acid modifications at unprecedented resolution. Through computational biology and bioinformatics approaches, it is now possible to identify, quantify, and characterize these modifications across the genome. This project aims to push the boundaries of what is known about nucleic acid modifications using state-of-the-art sequencing techniques and advanced computational methodologies.

PhD Project: Bioinformatics / Computational Biology of Nucleic Acid Modifications 

The successful candidate will:

• Analyze and integrate multiple sequencing data types (DNA-seq, ChIP-seq, RNA-seq, Methyl-seq, DRIP-seq) to study nucleic acid modifications and related epigenetic regulatory processes.

• Develop analysis pipelines for pre-processing, normalization, and statistical modeling of high-throughput sequencing data.

• Integrate and mine public datasets to complement in-house generated data and extract novel biological insights.

• Visualize complex data using advanced techniques for clear and informative presentation of results.

• Collaborate with experimental biologists and bioinformaticians to identify critical biological parameters and refine experimental designs through computational analysis.

Requirements

Applicants should have a strong background in bioinformatics, computational biology, or a related field. Proficiency in scripting languages (e.g., Python, R), and a solid understanding of high-throughput sequencing technologies are highly desirable. Familiarity with nucleic acid biology, epigenetics, or statistical modeling is a plus.

If you are interested in this project, please select Niehrs (Bioinfo) as your group preference in the IPP application platform.

Publications relevant for this project

Musheev MU, Schomacher L, Basu A, Han D, Krebs L, Scholz C, Niehrs C (2022) Mammalian N1-adenosine PARylation is a reversible DNA modification. Nat Commun. doi: 10.1038/s41467-022-33731-w Link

Parasyraki E, Mallick M, Hatch V, Vastolo V, Musheev MU, Karaulanov E, Gopanenko A, Moxon S, Méndez-Lago M, Han D, Schomacher L, Mukherjee D, Niehrs C (2024) 5-Formylcytosine is an activating epigenetic mark for RNA Pol III during zygotic reprogramming. Cell. doi: 10.1016/j.cell.2024.08.011 Link