We are looking for a motivated PhD candidate to join Dr Tineke Lenstra’s team. The main interest of the Lenstra lab is to understand the regulatory mechanisms and dynamics of eukaryotic transcription. Precise regulation of transcription is essential to ensure that the correct genes are expressed in the correct tissue at the correct time. Misregulation can result in diseases such as cancer. Understanding the molecular mechanisms that regulate transcription requires a dynamic view of the underlying process inside single cells. Such single-cell studies have shown that genes are transcribed in a highly dynamic manner, with bursts of transcription activity interspersed with periods of inactivity. In our lab, we use cutting-edge single-molecule microscopy techniques to directly visualize and quantify these transcriptional fluctuations inside single cells (e.g. Patel, Mol Cell 2023, Brouwer, Nature Struc & Mol Biol, 2023., Donovan, EMBO J, 2019, Lenstra, Mol Cell, 2015).

For this project, which is performed in collaboration with Jurgen Marteijns lab, we apply our live-cell imaging approaches to study the dynamics and fate of RNA polymerases when they encounter DNA damage during transcription. Transcription-blocking DNA damage can cause cellular dysfunction and cell death, eventually resulting in DNA damage-induced aging and genome instability. Surprisingly little is known about the molecular consequences of DNA damage on RNA polymerase itself. In this project we will use cutting-edge single-molecule imaging techniques 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.

Scientific environment
Located in Amsterdam, the Netherlands Cancer Institute (NKI) is an internationally renowned institute dedicated to fundamental, translational and clinical cancer research, and the only comprehensive cancer center in The Netherlands. It is a dynamic institute accommodating over 50 research groups and many excellent facilities, including for microscopy, flow cytometry, protein expression and purification, genomics, proteomics and many more. The laboratory is part of the division of Gene Regulation with multiple groups of complementary expertise. Moreover, the project will be carried out in collaboration with the Marteijn lab in Erasmus MC, where another PhD student will work on this project.

We are looking for a highly motivated and enthusiastic PhD candidate with a Msc. degree with a strong background in molecular biology with an affinity for biophysics, systems biology and quantitative biology. Good communication skills and the ability to work in a team are essential. Previous experience in the field of transcription regulation, DNA damage response or live-cell microscopy + image analysis would be advantageous.

Fixed-term contract: at least 4 years.

We offer a stimulating and interactive research environment, free use of all state-of-the-art facilities, a competitive salary. The gross salary per month can range from €3195,- to €3879,- (salary PhD scale according to the Collective Labour Agreement General Hospitals). In addition, you will receive 8,33% holiday pay and end-of-year bonus (8,33%). The appointment is for a period of at least four years.

You will join the OOA oncology graduate school, where you have the opportunity to follow high-quality courses.