PhD Student - DNA Break Signature in Cancers

The Brain Mosaics and Tumorigenesis Laboratory at the DKFZ investigates how the genome is shaped, maintained, and disrupted in health and disease. We are particularly interested in how replication stress, transcription–replication conflicts, and DNA repair pathways influence the formation of double-strand breaks, copy-number alterations, and other structural genome changes.

Our group combines cutting-edge genome biology approaches with quantitative, multi-omics analyses to uncover the mechanisms that generate and resolve DNA damage. We have developed and routinely apply high-resolution mapping technologies — including LAM-HTGTS for direction-resolved DNA break mapping, Hi-RepliSeq for replication timing and directionality, GRO-seq for nascent transcription, and DRIP-seq for R-loop detection. These methods allow us to integrate replication, transcription, and DNA repair features at nucleotide resolution across large genomic datasets.

We focus on cancer models (osteosarcoma, breast cancer, leukemia) and on neural progenitor cells to understand how genome instability contributes to tumor initiation, therapy resistance, and disease progression. By pinpointing cell-type-specific vulnerabilities in the genome, we aim to identify novel therapeutic targets and inform personalized treatment strategies.

Our research environment is highly collaborative and interdisciplinary, spanning genome biology, computational analysis, and translational cancer research. Members of the lab gain expertise in next-generation sequencing, genome-wide data integration, statistical modeling, and hypothesis-driven experimental design, preparing them for leadership roles at the interface of molecular biology and data science.

Project Description

Replication stress (RS) disrupts DNA replication and is a hallmark of cancer. RS often leads to DNA double-strand breaks (DSBs), which can fuel genomic instability but also reveal therapeutic vulnerabilities. In collaboration with the Aqeilan Lab (Hebrew University of Jerusalem, Israel), we aim to map RS-mediated and naturally occurring DSBs in cancer cells at nucleotide resolution.

Using advanced sequencing technologies, we will characterize DSB landscapes across osteosarcoma, breast, and leukemia cell lines and compare them with in vivo tumor models. This multi-omics approach will pinpoint cancer-specific DNA break hotspots and their association with transcription, replication dynamics, and RNA:DNA hybrid formation.

Goals of the PhD Project

• Map and classify RS-mediated and naturally occurring DSBs in distinct cancer cell types
• Integrate multi-omics datasets (DSB maps, replication timing/direction, transcription orientation, and R-loop profiles) to identify cancer-type-specific vulnerabilities
• Generate engineered cancer cell lines (in collaboration with a technician) and design hypothesis-driven analyses to identify targetable mechanisms of genomic instability
• Contribute to developing reverse-translational strategies for therapeutic interventions in osteosarcoma and breast cancer

Future Perspective

The project offers the opportunity to work at the forefront of cancer genomics using cutting-edge sequencing and integrative computational analyses. The successful candidate will gain expertise in multi-omics data integration, statistical and computational methods, and translational cancer research. Results from this work are expected to reveal new mechanisms of genome instability, inform RS-targeting therapies, and open avenues for personalized treatment strategies.

Your Profile 

• Major in biology, bioinformatics, or related fields (genetics, genomics, bioengineering, applied mathematics)
• Master’s degree or expected master’s degree in the above-mentioned fields
• (For biologists) Intermediate programming skills in R or Python, as well as prior experience analyzing omics datasets, are advantageous
• (For bioinformatic-mathematic traits) Good performance in biology courses at university
• Proficiency in English (spoken and written)
• Self-motivation, commitment, and the ability to work both independently and as part of a team

Interested candidates should submit a CV, a cover letter, academic transcripts, and contact details of two references via the application portal. Review of applications will begin immediately and continue until the position is filled.