Position 9

Exploring the genetic space of replication proteins.

PhD position in studying the role of resection factors in the replication stress response at the group of Dr Sylvie Noordermeer in the Department of human genetics at the Leiden University Medical Center in Leiden, The Netherlands.

What is the candidate going to do?

Resection factors play an important role during several pathways of DNA double-strand break (DSB) repair.  Recent research in our lab has now suggested that these factors also play important roles during replication, especially in cells defective for DSB repair. However, we lack mechanistic knowledge to explain their role. The candidate will perform CRISPR-screens in cells deficient for resection factors under perturbed and unperturbed replication conditions to study the genetic interactions of resection factors. This will allow us to better understand their role in safeguarding replication in different settings. Furthermore, the candidate will perform dedicated replication assays to study whether the resection factors play an active role at ongoing and/or stalled replication forks and whether they are involved in fork progression, restart or protection. By performing DSB assays and studying genomic instability, the role of resection factors for cellular homeostasis will be characterized. The candidate will be actively enrolled in the RepliFate community and will benefit from all extracurricular training. Furthermore, the candidate will perform secondments in other RepliFate institutes to broaden her/his scientific skills and broaden her/his network.

What does the candidate have to offer?
  • MSc in Molecular Biology and/or Biochemistry (or equivalent)
  • Highly motivated to perform curiosity-driven fundamental research
  • Strong knowledge of cancer biology
  • Good communication skills with a critical mindset
  • Strong skills in standard molecular biology techniques

Preference will be given to candidates that have (theoretical and/or practical) experience with DNA damage research and/or CRISPR-screens.

About the institution

The Department of Human Genetics at the Leiden University Medical Center is a broadly oriented research department, focussing on the (epi)genomic contribution to diseases. The department consists of 23 research units, embedded in four overarching research lines. You will work in the recently established research group led by dr. Sylvie Noordermeer which is embedded in the research line ‘Genome instability and cancer and has a clear focus on better understanding the fundamental mechanisms of DNA damage repair to improve clinical management of cancer patients. More specifically, the research in the Noordermeer lab governs the study of the protein BRCA1 and its regulation and function in multiple protein complexes involved in homologous recombination and genome stability maintenance. We complement our fundamental research in mammalian cell line models with studies on clinical data of BRCA1-mutated tumours to improve risk prediction and therapy approaches for the wide variety of BRCA1 mutations present in tumours. We have previously uncovered mechanisms involved in therapy resistance of BRCA1-deficient cells to PARPi (Noordermeer et al., Nature, 2018). Furthermore, projects in the lab address DSB repair pathway choice on a single cell level using advanced live-cell imaging and sequencing technologies. The LUMC hosts state-of-the-art facilities for proteomics, microscopy and high-content screening that we use for our research.

Any questions?

Do you have any questions or do you require additional information? Please contact: Dr Sylvie Noordermeer: s.m.noordermeer@lumc.nl.