PhD student to study mechanisms of DNA damage induced-transcription stress

Blockage of transcription by the gradual accumulation of DNA damage is a major driver of human neurodegeneration and aging. DNA damage obstructs elongating RNA polymerase II directly, leading to the initiation of transcription-coupled DNA repair to remove the DNA damage. DNA damage also indirectly causes genome-wide transcription shutdown, which is especially relevant when DNA damage persists, such as during cancer therapy and aging. Our lab specializes in transcription-coupled and other nucleotide excision repair–related DNA repair mechanisms (https://lanslab.eu/publications/). This project builds on our previous findings that persistent DNA repair intermediates interfere with transcription and are more detrimental than DNA damage itself, which can be found in e.g. Muniesa-Vargas et al, Nature Comm, 2024; van der Woude, bioRxiv, 2025; van Sluis et al, Nature Rev MCB, 2025).

The precise proteins and mechanisms that control transcriptional integrity upon persisting DNA damage are poorly understood. In this project, we will use forward genetic screens in the model organism C. elegans to identify new mediators of this transcription stress response. These new mediators will subsequently be functionally characterized using genetic and cell biological analysis, in combination with advanced DNA repair, live cell imaging and proteomics approaches, in both C. elegans and human cells. This research is expected to provide new insight into how DNA damage-induced transcription stress contributes to aging, neurodegeneration, and chemotherapy-related toxicity.

We are looking for a highly motivated candidate with a MSc degree in a relevant discipline (e.g. Molecular/Cell biology, Biomedical Sciences, Molecular Sciences, Life Sciences, Nanobiology). Experience with DNA repair research and/or with C. elegans is an advantage but not essential. The candidate should be able to independently design, conduct, and evaluate research projects; have outstanding theoretical and experimental research skills; and be well organized, result-driven, and a strong team player. Furthermore, a strong command of (scientific) English in speech and writing is essential (EUR requirements minimum IELTS overall score of 7.0 [comparable to TOEFL PBT: 600; TOEFL CBT: 250; TOEFL IBT: 95]). Being able to present a certificate of good conduct, a valid proof of identity are conditions for the appointment.

The department of Molecular Genetics at the Erasmus MC has a strong world-wide reputation in understanding the DNA damage response at the molecular, cellular and physiological level. The department consists of a vibrant and international group of more than 80 researchers working on various aspects of DNA damage, DNA repair and other DNA damage-related responses. This project will be carried out in the Lans DNA repair lab. The Lans DNA repair lab studies the molecular mechanisms of DNA repair in relation to disease, using genetics and molecular cell biology combined with live cell imaging and proteomics approaches, in C. elegans and human cells as model systems. Our group collaborates intensively with other groups within the department and collectively we have a strong international reputation in the field of DNA repair research. We offer a dynamic, challenging, and cooperative research environment and an excellent training and supervision platform through the PhD teaching program of our Erasmus MC graduate school.

The Erasmus MC stands for a healthy population and excellence in healthcare. By conducting groundbreaking work, we aim to push boundaries through leading the way in research, education and healthcare to improve and renew the healthcare of today and the public health of tomorrow. To stimulate research, the Erasmus MC provides access to the latest equipment and techniques in a state-of-the-art environment.

For more information about this position, please contact Dr. Hannes Lans, e-mail: w.lans@erasmusmc.nl.

For more information visit www.lanslab.eu.