In one project the PhD student will make use of CRISPR/Cas9 technology to inactivate several components of the endosomal sorting machinery to unravel the molecular organization of the endosomal sorting machinery in controlling plasma lipid levels. In the second project, the student will translate genetic information from humans to dedicated mouse models and cell systems and vice versa. Both projects will include experiments with cellular (e.g. primary mouse hepatocytes, fibroblasts) and mouse models to investigate the role of the candidate genes in cholesterol uptake, synthesis and secretion. Cells and tissues samples will be analyzed at the cell biological (immunofluorescence), transcriptional, and biochemical (proteomics) level. Under dedicated supervision, you will be responsible to successfully complete your PhD training program, present at national/international scientific conferences, and report in scientific renowned journals.

You have a MSc degree in molecular cell biology, biochemistry, genetics or medical biology, with a strong affinity to molecular biology and genetics. The candidate should be able to work in a team of fellow PhD students and technicians. We are specifically looking for PhD students with strong problem-solving capacities, creative thinking and with experience in molecular and cell biology techniques. Students with 1) working experience with mouse models, 2) certificate for Course on Laboratory Animal Science (Art. 9), 3) certificate for Course in radiation protection (5A or 5B certificate); 4) international research experience; 5) experience in metabolism, in particular lipid metabolism; 6) affinity with bioinformatics or genetic datasets; 7) strong English speaking, and writing skills will be selected with priority. However, enthusiastic talented students without these skills should not be scared off!

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

A fixed position of four years, 36.0 hours per week.
Your salary is € 2.279,- gross per month in the first year up to a maximum of € 2.919,- gross per month 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).

Additional information
Link: www.labpediatricsrug.nl
For more information about this vacancy you may contact:
- Prof. B. van de Sluis – a.j.a.van.de.sluis@umcg.nl
- Prof. J.A. Kuivenhoven – j.a.kuivenhoven@umcg.nl
(please do not use e-mail adresses for applications)

Application
Please submit your application including a letter of intent, detailed curriculum vitae, copies of your certificates, and a list of references.

Department of Pediatrics, section Molecular Genetics

The section Molecular Genetics of the Department of Pediatrics (University Medical Center Groningen, the Netherlands) is looking for two highly motivated PhD candidates with an education in molecular (cell) biology, medical biology, or genetics (bioinformatics) with a genuine interest in cell biology, lipid metabolism, and/or genetics.

Background
Cardiovascular disease (CVD) remains the number one cause of death worldwide. Atherosclerosis, the underlying pathology of CVD, is known as a lipid-driven inflammatory disorder. Although there are drugs that can successfully reduce the risk of CVD, there remains a substantial residual risk to resolve. Better insights into the biology of plasma lipid regulation will pave the road for novel treatment strategies.

Aims
Our primary goal is to increase our understanding of the regulation of plasma lipid levels in humans. In ongoing international (Transcard-FP7-603091) and national projects (GeniusII- CVON2017-2020), we have identified novel pathways and candidate genes involved in the regulation of plasma lipid levels. We uncovered that the endocytic system in hepatocytes is essential in the regulation of hepatic cholesterol metabolism and, consequently, in whole-body cholesterol homeostasis. Furthermore, genetic studies identified mutations in genes, which might explain low and high plasma lipid levels in humans. In this project, we will further investigate how the endocytic system is molecularly organized and, consequently, how it regulates hepatic cholesterol metabolism. In addition, functional studies will be performed to elucidate the contribution of the identified mutations on plasma lipid levels.

The Department of Pediatrics at the University Medical Center Groningen aims at understanding the molecular principles of metabolic health and mechanism underlying the development of inborn and acquired 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.

The section Molecular Genetics of the Department of Pediatrics is interested in understanding the etiology of various complex diseases, with a specific focus on inflammation, dyslipidemia and cardiovascular disease. In the recent years, we have developed a powerful combination of techniques (e.g. CRISPR/Cas9 technology, proteomics) and in vivo models to study molecular mechanism that are involved in the above-mentioned pathologies.