PhD Pediatric cholestatic diseases studied and treated via genetic mouse models
Department
Kindergeneeskunde
Working Enviroment
The Section of Molecular Metabolism and Nutrition of the Department of Pediatrics studies the molecular underpinnings of health and disease with a focus on inborn and acquired diseases. Progressive Familial Intrahepatic Cholestasis (PFIC) stands for a group of rare, severe liver diseases in children, which refquently lead to the need of liver transplantation during childhood. Although liver transplantation has become a valuable and life-saving treatment for these diseases, strategies to delay or even avoid the need for liver transplantation are most welcome. Recently major progress has been made in the development of medical therapies that directly target bile acid metabolism and transport. Our section has actively contributed to this progress and we aim to further improve the treatments for patients with PFIC disease.
The identification of the underlying gene defects in PFIC allows to further characterize the mechanisms by which the involved gene products lead to liver damage and to assess targets of therapeutic intervention. This knowledge will improve our mechanistic understanding of these diseases and enhance effective prevention and treatment. We are eager to educate and train the next generation of academic professionals.
Information about the laboratory of Pediatrics
Job description
Progressive Familial Intrahepatic Cholestasis (PFIC) stands for a group of rare, severe liver diseases in children. Different types of PFIC have been identified, based on loss-of-function mutations in several genes involved in bile formation, leading to bile acid-induced liver damage. Patients with PFIC develop progressive deterioration of liver function that frequently evolves in the need for liver transplantation. The treatment of patients with PFIC diseases has long been largely symptomatic, but more recently major progress has been made, including the development of medical therapies that directly target bile acid metabolism and transport.
The identification of the underlying gene defects in PFIC allows to further characterize the mechanisms by which the involved gene products lead to liver damage and to assess targets of therapeutic intervention. The rarity of these diseases, however, neccessitate studies in model systems, including in genetically modified mouse models for these diseases that are currently being generated using state-of-the-art technology. The present PhD project will address the mechanisms of liver damage of PFIC diseases in relevant model systems and evaluate the effects of targeted interventions to prevent or mitigate this damage. Techniques that will be applied during the project include quantification of bile acid transport in in vitro as well as in vivo model systems, molecular cloning and adeno(-associated) virus production and transduction techniques, transcriptomics, proteomics, and histology/immunohistochemistry. You will work in a team consisting of PhD-students, post-docs and technicians that are supervised by principal investigators.
Requirements
- MSc degree in (medical) biology, medicine or related discipline;
- Experience in laboratory techniques;
- Interest in physiology and in clinically oriented research in model systems;
- Strong motivation to succeed in scientific research;
- Independent and well-structured working style;
- Accurate and flexible;
- Well-developed social skills directed to work in a team.
Conditions of employment
A temporary fulltime contract (36 hours a week) for the period of four years. Your salary will be a minimum of € 2.789,- gross per month in the first year and a maximum of € 3.536,- gross per month (scale PhD) in the final (4th) year, based on a full-time appointment. In addition, the UMCG will offer you 8% holiday pay, and 8.3% end-of-year bonus. The conditions of employment comply with the Collective Labour Agreement for Medical Centres (CAO-UMC).
Additional information
For more information about this vacancy you may contact:
Prof. dr. Henkjan Verkade
telefoonnummer +31 50 361 1261
h.j.verkade@umcg.nl
Dr. Jan Freark de Boer
telefoonnummer +31 50 361 4865
j.f.de.boer@umcg.nl
Applying for a job
Please use the the digital application form at the bottom of this page - only these will be processed.
You can apply until 23 February 2023.
Within half an hour after sending the digital application form you will receive an email- confirmation with further information.
Digital application form