Within the group of Hans Jonker we are seeking a Postdoc and a PhD student for the project entitled “Targeting the ER stress response in non-alcoholic fatty liver disease” which is funded by a VICI grant from ZonMW. We offer a challenging project in a well-organized, international, and high-profile research group within the University Medical Center Groningen.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the most serious pathologies associated with obesity, yet there is still no approved pharmacologic treatment option. Suboptimal functioning of the endoplasmic reticulum (ER), the organelle central to synthesis and folding of secreted and transmembrane proteins as well as of biosynthesis of lipids, has been proposed to contribute to NAFLD. The underlying mechanisms, however, have remained largely elusive. Hepatic ER stress can contribute to the accumulation of lipids (steatosis) and progression of NAFLD by inhibiting lipid secretion or burning (ß-oxidation), promoting synthesis (lipogenesis) or by increased lipid uptake due to insulin resistance. Conversely, hepatic ER stress can also be exacerbated by steatosis as a result of the accumulation of toxic lipids (lipotoxicity), thereby creating a vicious cycle. ER stress and steatosis thus represent a “perfect storm” heralding the development of NAFLD. Therapeutic approaches that interrupt this cycle should therefore ameliorate NAFLD.

The aim of this Vici project is to define the molecular mechanism by which modulation of the unfolded protein response (UPR), an adaptive process that regulates ER homeostasis, affects hepatic lipid secretion and how this can be used in the treatment of NAFLD. The following key objectives will be addressed: (i) to dissect the UPR pathway at the molecular level and establish its effect on chaperone-mediated folding of components of the lipid secretory machinery; (ii) determine the physiologic and therapeutic consequences of its modulation for hepatic lipid secretion using cellular and mouse models of NAFLD, and (iii) examine its therapeutic and diagnostic potential in NAFLD using iPSC-derived hepatocytes and liver biopsies of patients.

-Degree in (medical) biology or related discipline
-Experience with molecular & cell biology
-Experience in proteostasis or ER stress is an advantage
-Experience with animal research is an advantage
-Interest in physiology and clinically-oriented research
-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

The UMCG has a preventive Hepatitis B policy. The UMCG can provide you with the vaccination, should it be required for your position.

In case of specific professions a ‘Certificate of Good Behaviour’ is required.

Estimated maximum Postdoc salary gross per month: € 4.216,- (scale 10), depending on your qualifications and relevant experience, based on a full-time appointment.
Estimated maximum PhD student salary gross per month: € 2.279,- in the first year, up to a maximum of € 2.919,- in the last year (scale PhD).

In addition, the UMCG will offer you 8% holiday pay, an 8.3% end-of-year bonus and a development budget. The terms of employment comply with the Collective Labour Agreement for Medical Centers (CAO-UMC).

Employment basis: temporary for specific period
Duration of the contract: four years
Maximum hours per week: 36

Additional information
Information can be obtained from:
Prof. dr. Johan W. Jonker
Phone: +31-503611261
E-mail: j.w.jonker@umcg.nl (please do not use for application)
Information about the laboratory of Pediatrics: www.labpediatricsrug.nl

Department of Pediatrics, Section of Molecular Metabolism and Nutrition

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 metabolic diseases. The ability to regulate energy metabolism is essential for life. Nutrient sensors play a pivotal role in regulating energy metabolism: metabolic disturbances initiate chronic diseases and contribute to their complications. Development of these systems in early life is affected by nutrition and linked to the risk of metabolic disease later in life. We strive to gain insight into the molecular mechanisms underlying deregulated metabolism in order to develop new strategies to prevent or treat metabolic diseases. This knowledge will be applied to improve diagnostics and/or effective prevention and treatment. We are eager to educate and train the next generation of academic professionals.