PhD student (two) Mutational footprints cancer predisposition

Organisation

The Princess Máxima Center for Pediatric Oncology is a recently started, fast growing research hospital for children with cancer. The institute houses an increasing number of research groups, which aim to develop cures for all children with cancer with minimal long-term side effects of existing treatment.

Three research groups have a joined research project entitled: “Mutational footprints of cancer predisposition”, for which they are now looking for two enthusiastic PhD students.

 

The Kuiper group (Childhood Cancer Genetics and Predisposition) aims to identify and investigate genetic aberrations involved in the process of cancer initiation and progression in order to understand genetic predisposition and disease recurrence.

The Van Boxtel group (Cancer Etiology) studies the molecular causes of childhood cancer and treatment-associated second malignancies with a focus on identifying mutational processes that drive cancer development across different tissues.

The Drost group (Molecular Dissection of Renal and Rhabdoid Tumors) uses state-of-the-art pre-clinical cancer models, including 3D organoids, to study fundamental processes driving tumor growth, such as intratumor heterogeneity and therapy resistance.

 

Research Project

The overall mutation burden of somatic cells is determined by a balance between DNA damage and repair activity. Germline mutations in key components of DNA damage response and repair can cause DNA repair disorders that predispose to cancer development.

Deficiencies in DNA damage response and repair in tumors leave specific mutational footprints, called mutational signatures. These signatures can be used as a direct functional readout of specific DNA repair defects and can therefore be a valuable tool in the cancer diagnostics, both for detecting inherited DNA repair disorders and somatically-acquired DNA repair deficiencies.

The aim of this proposal is to systematically define the mutational footprints associated with DNA repair deficiencies in tumors in order to improve the recognition of DNA instability syndromes in children with cancer. Furthermore, we aim to predict resistance or hypersensitivity to DNA damaging chemo- and radiotherapy in these patients and identify novel vulnerabilities for treatment.

 

Tasks and responsibilities

We are looking for two enthusiastic and ambitious PhD students who are highly motivated to take on this challenge. The PhD students will be responsible for extracting mutational spectra and signatures from whole genome sequence data obtained from patients with established DNA repair syndromes (PhD1) and from in vitro cell culture models, such as organoids, in which these DNA repair defects will be introduced (PhD2). The PhD students will work in a strongly integrated team of researchers and clinicians, and will be supported by experienced bioinformaticians present in the groups.

 

Education and skills

  • Completed master in biomedical/molecular sciences or medicine with strong drive to perform a PhD in pre-clinical science.
  • Affinity with genetics and genomics
  • Affinity with cell culturing and CRISPR/Cas9-mediated gene editing
  • Strong drive for a career in science
  • Independent and creative working style
  • Strong communicative skills
  • Good writing and presenting skills
  • Self-critical mindset

 

Working at the Princess Maxima Center for Pediatric Oncology

We offer two challenging fulltime PhD positions in an inspiring research environment. You will follow the PhD training programme of the research school Cancer, Stem Cells & Developmental Biology, which is part of the Utrecht graduate school of Life Sciences.

The total duration of the project is 4 years. You will initially be appointed for a period of 1 year, during which your performance will be evaluated by a training and supervision plan.

Salary according to FWG 45 increment 6 (for the 1st year, increased to FWG 45 increment 10 in case of renewal). The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’.

 

Apply for this position?

You can apply for this position until March 1st by pressing the apply button on this screen.

We welcome you to contact Dr. R.P. Kuiper (r.kuiper@prinsesmaximacentrum.nl) for additional information about the vacancy. Detailed information about the Princess Máxima Center for Pediatric Oncology can also be found at www.prinsesmaximacentrum.nl.

Acquisitie naar aanleiding van deze vacature wordt niet op prijs gesteld.

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