Environmental genotoxins and metabolic by-products generate DNA lesions which can cause genomic instability and drive carcinogenesis. To ensure genomic integrity, cells employ mechanisms that convert signals generated by stochastic DNA damage into organized responses including activation of repair systems, cell cycle checkpoints and apoptotic mechanisms. We have identified a novel, DNA damage response (DDR) pathway that initiates in response to transcription-blocking DNA damage and activates the master DDR coordinator ATM, through mechanisms involving spliceosome remodeling and formation of potentially genotoxic R-loops. DDR has received considerable attention as therapeutic target for cancer and a full understanding of the mechanisms underlying this novel DDR-related pathway involving R-loops might represent exceptional opportunities to achieve better understanding of cancer biology and to develop more precise cancer therapies.

This project, which is funded by the Word Wide Cancer Research (WWCR), aims at elucidating the exact mechanism of ATM activation by R-loops and how the latter are resolved to prevent further genomic instability. To this end, a multidisciplinary approach, using various biochemical and DNA repair assays, live cell imaging and quantitative proteomics will be pursued. Acquired knowledge will be applied to devise cancer-type-specific synthetic lethality strategies by using unconventional combinations of chemotherapeutics and cancer-unrelated approved drugs that can interfere with this pathway.

We are looking for highly motivated and talented candidates holding a PhD degree in Molecular/ Cellular Biology, Biochemistry or related field. Experience with biochemical assays, live cell imaging and proteomic tools is required as well as a strong theoretical basis in the field of genome stability. Specific knowledge on the current state-of-the-art developments in DNA damage signaling will be a strong advantage. The candidate should be able to independently design, conduct and evaluate research projects, to assemble experimental data into a publishable manuscript and willing to work in a collaborative team.

Being able to present a certificate of good conduct is a condition for the appointment.

We offer a position for 1 year, with the possibility of extension for 2 more years. The gross monthly salary amounts a maximum of € 4.216,- (scale 10), depending on your level of education and relevant experience and based on a full-time working week of 36 hours. The terms of employment are in accordance with the Collective Bargaining Agreement for University Medical Centers (CAO UMC).

Erasmus MC

A healthy population and excellence in healthcare through research and education. This is what Erasmus MC stands for. Conducting groundbreaking work, pushing boundaries and leading the way. In research, education, and healthcare. We are practical people with a high level of expertise, working hard to improve and renew the healthcare of today and the public health of tomorrow.

The research group of Prof. W. Vermeulen at the Department of Molecular Genetics of Erasmus MC performs innovative fundamental and applied research on genome stability. The group uses a multidisciplinary approach to advance understanding of the molecular mechanisms that protect our genome, working from the molecular genetic, biochemical and cell biological level to the level of intact eukaryotic organisms and patients. The group of 12 researchers works in a highly collaborative and integrative manner with a strong focus on live-cell imaging and proteomic tools. Our group acts internationally at the forefront of DNA repair and offers a dynamic, challenging, and cooperative research environment