PhD student

Last application date
Feb 28, 2018 23:59
Department
GE02 - Department of Pediatrics and medical genetics
Contract
Limited duration
Degree
Master’s Degree in Biomedical Sciences, Bioengineer, Biochemistry or a closely related subject
Occupancy rate
100%
Vacancy Type
Research staff

Job description

Project title:

Heading for an in vivo predictive test for cancer therapy: application of PARP inhibitor therapy in zebrafish patient derived xenografts

PARP inhibitors (PARPi) are a novel treatment strategy and already reimbursed for treatment of ovarian cancer patients with germline BRCA1/2 mutations. Clinical trials in other tumour types are ongoing and showed that PARPi treatment may also be effective in other tumour types when a pathogenic BRCA1 or BRCA2 mutation is present. Moreover, PARP inhibitors might also target tumours with mutations in other genes involved in the repair of DNA double strand breaks through the Homologous Recombination (HR) pathway. PARP inhibitors work by blocking the Base Excision Repair (BER) pathway, which is lethal in cells who have no functional HR pathway, a term coined “synthetic lethality”. Indeed, tumour cells defective of both the HR and BER pathways undergo apoptosis, while somatic cells with functional HR will survive.

In this project, zebrafish will be used to assess the effectiveness of different PARP inhibitors.

In a first part, we will further optimise DNA damage repair assays in zebrafish after treatment with PARP inhibitors. Our research team recently published a first assay to quantify DNA damage repair by RAD51 foci in zebrafish (PMID: 29184099); more assays are currently under development. The team has a lot of experience with such assays in human cells (e.g. PMID: 29154021, 27184744, 23632773, 28184943). In a second part, zebrafish patient derived xenografts (zPDX) from tumour biopsies with a known BRCA status will be exposed with PARP inhibitors. Following exposure, tumour response will be analysed through measuring tumour growth, apoptotic and mitotic activity. In addition to PARP inhibitor monotherapy, a combination of PARP and irradiation (chemoradiation therapy) will be performed. This study will allow to 1) evaluate the responsiveness of the patient to adjuvant therapy, and 2) developing novel treatment strategies in the fight against cancer.

As a final goal, genome wide sequencing will be performed on these tumours with the goal of discovering novel markers for (non)-responsiveness to treatment.

Profile of the candidate

We are looking for an enthusiastic and ambitious PhD student, who holds a Master’s Degree in Biomedical Sciences, Bioengineer, Biochemistry or a closely related subject, with excellent grades and a strong interest in (human) genetics and radiobiology.

Moreover, the candidate should be highly motivated, with strong interest in the field of (hereditary) cancer. You should be capable of working independently as well as in a team setting. The candidate has excellent skills in wet lab work (immunohistochemistry, cell culture, microscopy, microinjection techniques, PCR, sequencing) and interested in data interpretation and (statistical) analyses.

You should be willing to work with zebrafish (larvae), and have an approval (or obtain an approval) to work with animals (equivalent to experimental manager, cat.C). The candidate should have good communication and reporting skills, a high level of proficiency in English while proficiency in Dutch is an asset.

How to apply

The application must include:

  • One-page statement of motivation and research interests
  • Detailed Curriculum Vitae (with individual course results)
  • Copies of educational certificates
  • Names and contact details of at least 1 reference

All documents should be in English. Any questions related to the position can be directed to prof. dr. ir. Kathleen Claes at the following e-mail address: .