Pheochromocytomas and paragangliomas (PGLs) are rare tumors of parasympathetic and sympathetic paraganglia, which secrete excess catecholamines, giving severe headache, panic attacks, arrhythmias and hypertension. Mostly, germline mutations confer susceptibility for PGL development leading to hypoxia-inducible factor-1/2α (HIF-1/2α)-dependent tumorigenesis. Among these are inactivating mutations in genes encoding Krebs cycle proteins, such as succinate dehydrogenase (SDH) subunits A-D, of which mutations in SDHB predispose to a high level of malignancy. Treatment of metastatic SDHB PGLs, however, is lacking and thus appropriate model systems and specific therapeutic targets for these tumors are urgently needed.

Using CRISPR/Cas technology, we have recently established zebrafish in which SDHB is systemically and tissue-specifically knocked out. The goal of the present project is to characterize the obtained transgenic zebrafish, study the aetiology of the disease, and to screen/test potential therapeutics.
The project is part of the international ‘paradifference’ consortium and is a collaborative project of the departments of Internal Medicine (section Endocrinology) and Physiology. The department of Internal Medicine has a long-standing tradition to molecularly analyse and treat PGL patients, whereas the department of Physiology has a strong expertise in molecular, cellular and animal pathophysiology.

In this project, you will work within the department Physiology, which is, together with basic science and research-oriented clinical departments of the Radboud University Medical Centre, housed in the Radboud Institute for Molecular Life Sciences (RIMLS), which integrates diverse scientific expertise in molecular and medical science for the advancement and innovation in translational research.

Tasks and responsibilities

• Generation and maintenance of SDHB-mutated zebrafish;
• Biochemical/bio-informatical analysis of the PGL phenotype;
• Setting up a cellular screening system for the potential therapeutic target;
• Data analysis and interpretation;
• Contribution towards preparation and submission of manuscripts;
• Presentation of data and communication with research partners.

• A PhD in molecular/cellular physiology/endocrinology or related field;
• A permit to work with animals (art. 9);
• Experience in the generation,handling and analysis of transgenic zebrafish;
• Organized working style;
• Good English writing and presentation skills;
• A strong motivation, flexibility, and willingness to learn;
• The ability to work and interact with others in an energetic and supportive research group;
• You recognise yourself in the Radboud way of working.

Fixed-term contract: 1 year with a possible extension.

Scale 10.4: max. € 44687 gross income per year at full employment (incl. vacation bonus and end of year payments).

Upon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG) and there will be a screening based on the provided CV. Radboud university medical center’s HR Department will apply for this certificate on your behalf.

Read more about the Radboudumc employment conditions.

Radboudumc (university medical center)

Radboudumc strives to be a leading developer of sustainable, innovative and affordable healthcare to improve the health and wellbeing of people and society in the Netherlands and beyond. This is the core of our mission: To have a significant impact on healthcare. To get a better picture of what this entails, check out our strategy film.

Our key strength is medical life-sciences and clinical practice, with an impressive infrastructure comprising state-of-the-art technology platforms and (translational) research facilities. The Radboudumc is therefore uniquely positioned in the emerging Euregio and Dutch healthcare infrastructure to play a leading role in the new healthcare paradigm of prediction, prevention and personalised medicine.

The Radboudumc focuses on scientific health challenges of today, with an eye on emerging diseases of the future.

Read more about what it means to work at Radboudumc and how you can do your part.

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