Postdoctoral Researcher Genome instability in cancer

Homologous recombination (HR) is an essential mechanism to repair toxic DNA breaks. Consequently, loss of HR impairs genomic stability and is therefore strongly associated with cancer development. For example, hereditary mutations in the HR-genes BRCA1 and BRCA2 are well-described to predispose to the development of breast and ovarian cancer. Interestingly, HR-deficient tumors are highly sensitive to specific therapeutics like PARP inhibitors. Identification of HR-deficiency can therefore guide therapy choice in the clinic. However, our knowledge on the genetic causes of HR-deficiency is incomplete. In this project, we therefore aim to expand our understanding of the genes that are involved in DNA break repair by HR, and to identify the associated genetic alterations in cancer that cause HR-deficiency.
The project is funded by recently awarded grants of the Dutch Cancer Society and the UMCG Cancer Research Fund, and can be divided into two research lines. First, we aim to identify HR-inhibitory genes that cause HR-deficiency and PARP inhibitor sensitivity upon overexpression in cancer. This will be done by state-of-the-art CRISPR activation screens using engineered DNA break repair reporter cell-lines. In the second research line, we will follow up on our recent identification of VHL, which is a tumor suppressor gene that is frequently mutated in kidney cancer, as an HR-promoting factor. Using a broad spectrum of genetic, proteomic, molecular and cell biology techniques we aim to mechanistically unravel the HR-defect caused by VHL mutations, and to delineate how this affects sensitivity to therapeutics that target this HR-deficiency.

The Postdoctoral Researcher will be part of an enthusiastic and multidisciplinary research group and should have the following requirements:
- A PhD in Medical or Molecular Biology.
- Experience in molecular and cell biology techniques (cell culture, DNA cloning, western blotting, microscopy, CRISPR/Cas9 gene editing, next-generation sequencing).
- An enthusiastic, self-motivated, ambitious, and proactive team player.
- Good communications skills in written and spoken English.

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