Projects Offered

Joint project between Beli and Roukos groups

1 PhD project offered in the IPP summer call 2025

Scientific Background

DNA double strand breaks (DSBs) are toxic DNA lesions that can arise from cell intrinsic and extrinsic sources and can lead to genome rearrangements in cancer. In eukaryotic cells, DSBs are formed, detected and repaired in the context of chromatin, made of nucleosomes where the DNA is wrapped around histone octamers. The DNA damage response (DDR) therefore needs to be integrated in the very plastic and dynamic chromatin landscape, and indeed recent studies have shown that chromatin alterations and the nuclear architecture actively contribute to the DDR and the utilization of the downstream repair pathways. However, how the differential DDR activation across the genome and in various chromatin and chromosome organization environments, is linked with the repair efficiency and fidelity at these locations, is poorly known, due to the lack of technologies to systematically tackle these questions.

PhD Project: Linking DDR activation with repair fidelity at different genomic, chromatin and chromosome organization contexts

This project aims to fill this gap in knowledge by combining quantitative mass spectrometry-based proteomics, CRISPR/Cas genome targeting and targeted next generation sequencing technologies. The goal is to systematically link DDR activation with changes in protein recruitment and histone modifications to kinetics of DNA repair efficiency and fidelity across various genomic & chromatin environments and in the context of chromosome organization. More specifically, we will employ targeted proximity-based proteomics to profile DDR activation at targeted DSBs induced by CRISPR/Cas technologies and profile kinetics and fidelity of DNA repair by NGS based methodologies we have established in the lab, to systematically link DDR activation with repair outcome across the genome. This project will help us understand how cells activate DDR to repair their DNA efficiently, with high fidelity, and has important implications for understanding how mutations are formed and to improve the predictability and precision of gene editing. 

If you are interested in this project, please select Beli/Roukos (BelRouk) as your group preference in the IPP application platform.

Publications relevant to this project

Mosler T, Conte F, Longo GMC, Mikicic I, Kreim N, Möckel MM, Petrosino G, Flach J, Barau J, Luke B, Roukos V and Beli P (2021) R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability.Nat Commun, 12:7314 Link

Longo GMC, Sayols S, Kotini AG, Heinen S, Möckel MM, Beli P, Roukos V. (2024) Linking CRISPR-Cas9 double-strand break profiles to gene editing precision with BreakTag.Nat Biotechnol. 13:s41587. Link

Contact Details

Petra Beli

Professor for Quantitative Proteomics
Institute for Developmental Biology and Neurobiology (iDN)
University of Mainz

Group Leader and Adjunct Director
Institute of Molecular Biology gGmbH (IMB)
Ackermannweg 4, 55128 Mainz, Germany

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Email
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Vassilis Roukos

Group Leader
Institute of Molecular Biology gGmbH (IMB)
Ackermannweg 4, 55128 Mainz, Germany

Assistant Professor
Medical School, University of Patras,Greece

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