PhD to study lysosomal cholesterol handling in metabolic diseases

Cholesterol is an essential lipid component of membranes and is a precursor of a wide range of signalling molecules. Disturbed cholesterol homeostasis is predominantly associated with the development of cardiovascular disease, but it is now well-recognized that this also plays a critical role in, amongst others, metabolic-associated fatty liver disease (MASLD) and its transition to hepatocellular carcinoma, cancer in general, and neurodegenerative diseases (e.g. Niemann-Pick disease and Alzheimer’s Disease). Our group is interested in elucidating the molecular regulation of lipid metabolism, and in this ZonMW funded project you will focus on the role of the lysosome in cholesterol handling, and specifically on cholesterol trafficking from this organelle. 

The lysosome is an essential cholesterol-trafficking hub, as is clearly illustrated in lysosomal cholesterol diseases such as Niemann-Pick disease (NPC). Cholesterol exit from the lysosome is tightly coordinated, but the molecular determinants involved are not fully known. In this PhD project, you will use genetic screens, CRISPR/Cas9-mediated genome-editing, proximity proteomics, cell-based functional assays, and advanced metabolic mouse models to identify and study novel mechanisms that govern lysosomal cholesterol handling. Our goal is to elucidate control of lysosomal cholesterol egress, so as to understand how this contributes to disease development when proper control is lost. 

For this 4 year PhD position in the research group of Prof. Noam Zelcer we are looking for an enthusiastic candidate that meets the following requirements: 

• A highly-motivated PhD candidate with an MSc in Medical Biology, Life Sciences, Biochemistry, or related field.
• Relevant experience in molecular and cell biology techniques (e.g. cell culture, CRISPR, proteomics, microscopy, etc.)
• Previous experience with cell and animal models (e.g. Article 9 of the Experiments on Animals Act) is preferred.
• Ability to work within a collaborative and international research group.
• Excellent command of oral and written English.
• Organizational talents and self-driven spirit.