PhD-student to study the effects of DNA damage on transcription

Correct gene transcription by RNA polymerase II to transcribe new RNA molecules is crucial for proper cell function. However, transcription by RNA polymerases can be blocked by DNA damage, for example by UV-light or other chemicals. This transcription-blocking DNA damage can therefore cause cellular dysfunction and cell death, eventually resulting in DNA damage-induced aging and genome instability. Cells counteract these deleterious effects by transcription-coupled repair (TCR), which specifically removes DNA damage in our genes, thereby safeguarding transcription. Our lab has identified several important factors that provided novel insights in this repair pathway (van Sluis et al., Nature Cell Biology 2024; Ramadhin et al., Molecular Cell 2024; van Toorn et al., Molecular Cell, 2022; Geijer et al., Nature Cell Biology, 2021; Tresini et al. Nature, 2015; Schwertman et al. Nature Genetics, 2012).

Surprisingly little is known about the molecular consequences of DNA damage on RNA polymerase itself. This is an important question to solve, as DNA damage-stalled RNA polymerase causes bigger problems for the cells than the actual DNA damage itself. In this project we will use innovative single molecule imaging procedures in combination with CRISPR-Cas9-mediated gene editing to for the first-time study the effect of DNA damage on RNA polymerases in living cells. This project will provide important molecular insights in how DNA damage affects Pol II and interferes with the transcription process, thereby improving our understanding of the cellular mechanisms that protect transcriptional integrity, which is essential to understand why organisms age.

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, Nanobiology). Experience with the basal transcription process, DNA damage response, live cell imaging, or with image analysis 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, is well-organized and result-driven with a strong team spirit. 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 ( https://www.erasmusmc.nl/en/research/departments/molecular-genetics ) has a strong world-wide reputation in understanding the DNA damage responses 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 Marteijn lab (www.genomestability.nl) at the Erasmus MC in a collaborative project with the Lenstra lab (https://www.nki.nl/research/research-groups/tineke-lenstra/) at the NKI where another PhD student will work on this project. The Marteijn lab studies the molecular mechanisms how cells deal with DNA damage that interferes with transcription, using a multidisciplinary approach using molecular and cell biological approaches. Our lab works in a highly collaborative manner with a strong focus on state-of-the-art live-cell imaging, genetic and proteomic tools. Our group acts internationally at the forefront of DNA damage and transcription stress. 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 (https://www.erasmusmc.nl/nl-nl/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.