Hereditary motor and sensory neuropathies collectively known as Charcot-Marie-Tooth (CMT) disease are a diverse group of neuropathies ranging from pure motor neuropathies to sensory disorders and from mild to severe types of disease even within families. CMT has an estimated prevalence of one in 2500 and is thus one of the more prevalent rare inherited diseases. Despite the identification of many gene defects causing the disease, no cure is currently available. The latest scientific insights point towards dysregulation of intracellular cholesterol trafficking and synthesis as common disease related pathway in demyelinating CMT. In this project, funded by the “Prinses Beatrix Spierfonds”, you will analyze the impact of dysregulation and deficiency of cholesterol and lipid synthesis in animal models of CMT1A. You will extend and integrate the RNAseq data with the lipidomics data set to identify the pathways underlying the downregulation of lipid metabolism. You will perform in vivo experiments to rescue the defect in lipid synthesis by cholesterol/lipid supplementation in the PMP22 overexpressing mouse models and determine the effect on function. You will analyze CMT patient SC differentiated iPS cells or SC from our CMT patient biobank for defects in cholesterol trafficking and lipid synthesis. Then you will evaluate the effects of lipid supplementation and lipid inhibition in these CMT patient cells.

The ideal candidate for this position has a proven background in (medical) biology or biomedical sciences and you ideally also have experience in neuroscience and/or cholesterol metabolism. An interest in and willingness to learn bioinformatic analyses is a must, and experience is a big plus. This project makes extensive use of genetically modified mouse models, so a license to work with animals in research, or willingness to obtain this, is essential. Finally, to work in this project, you will require a broad biological interest and a flexible work attitude.

Fixed-term contract: 4 years.

You will be given an employment contract for the production of a PhD thesis for the duration of the program with a maximum of four years. The salary amounts to € 2,495 gross per month in the first year, up to a maximum of € 3,196 in the last year with fulltime employment (scale Pro, CAO UMC).

LUMC

At the Leiden University Medical Center, we continuously work on improving patient care. We invest in groundbreaking, international research and work with the latest equipment. Together with our team of doctors, medical specialists, teachers, academic researchers and supporting staff, we aim for the best quality in health care, education and international research. And we need you to realize our goals!

Department of Clinical Genetics

The department of Clinical Genetics is a broadly oriented clinical and research department, led by professor Christi van Asperen and professor Frank Baas who oversees the Clinical and Research Laboratory (LDGA) of the Clinical Genetics department. The research of the Frank Baas lab is focused on genetic disease and the functional biochemical and cellular consequences. Using this knowledge we try to improve patient care with better diagnostic tests, functional assays and develop new insights for potential treatments. For this we use a combination of in vitro and in vivo model systems.