Polycystic liver disease (PLD) is an inherited disorder characterized by the development of multiple fluid-filled cysts in the liver. PLD is found in patients with autosomal dominant polycystic liver disease (ADPLD) and in patients with autosomal dominant polycystic kidney disease (ADPKD). Patients may present with hepatomegaly and abdominal complaints, but usually have normal liver enzymes.

The first gene (PRKCSH) associated with ADPLD was discovered by our laboratory. Since then more genes have been associated with ADPLD. Nevertheless only about 35% of patients can be explained by mutations in these genes. The genes identified so far are expressed in numerous tissues, yet the phenotype reveals itself specifically in the liver. It is still not known why the phenotype is restricted to the liver and which liver-specific mechanisms are responsible.

We hypothesize the liver restricted phenotype results from a liver-specific pathway that is affected in all PLD patients. Your job will be to identify elements of this liver-specific molecular signature affected in PLD.

The following objectives could be addressed:

• Identification of new genes involved in PLD using whole exome/genome sequencing and microarray;
• Create transcriptomic and proteomic expression profiles with RNAseq and tandem mass spectrometry to reveal pathways involved in cystogenesis;
• Funtional studies of (new) identified genes in in-vitro/in-vivo models.

For this project we have access to biomaterials of PLD patients including whole blood, cystic tissue, cyst fluid and organoids. This project is funded by the Radboud Institute of Molecular Life Sciences.

• Master in Medical Biology, Biomedical Sciences, Medicine or equivalent discipline;
• High affinity for translational research related to gastrointestinal and hepatological disorders including various omics approaches (e.g., genomics, proteomics);
• Experience with in vitro and in vivo modeling using cell lines and Zebra Fish (Article 9 of the Dutch Law on Animal Experimentation is an advantage);
• Experience with molecular and cell biology;
• Good social skills and able to work in a team.

You will be appointed as a PhD student at the Radboud university medical center Nijmegen, Department of Gastroenterology and Hepatology, with the standard salary and secondary conditions for PhD students at the department. You will work within the Radboud Institute for Molecular Life Science (RIMLS). You are offered a three-year full-time employment.

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

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Radboudumc

Department of Gastroenterology and Hepatology: Better and better together!
You will be working with approximately 200 colleagues within the ambitious department of Gastroenterology and Hepatology of the Radboud university medical center (Radboudumc). Our department consists of a clinical nursery together with abdominal surgery, an outpatient clinic, an endoscopy center, a clinical trial unit and a laboratory for translational research. Additionally, the dietetics department is part of Gastroenterology and Hepatology.

Our main goal is to treat all patients with gastrointestinal diseases and has a special focus on the themes Inflammatory Bowel Disease, Oncology, Intestinal failure & Total Parenteral Nutrition, Hepatology, and Advanced Endoscopy. We distinguish ourselves by the synergy between personal healthcare, education, training, and high quality research. Besides clinical research performed on every theme by multiple PhD students, the department has its own well equipped research laboratory where translational research is performed with the help of several technicians.

Radboudumc
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.

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