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.

• A flying start to your career in scientific research.
• Plenty of room for your drive to shape tomorrow's healthcare.
• Working on large-scale and in-house research, with motivated colleagues from all over the world.
• You will be employed by Amsterdam UMC Research BV.
• A contract for 12 months, with the intention to extend for a total of 4 years. The Guideline PhD contract applies to this vacancy.
• Salary scale OIO: € 3.017 to € 3.824 gross based on full-time employment (depending on education and experience) and a year-end bonus of 8.3%. Calculate your net salary here. From July 1st, 2025, there will be a salary increase of 3%, up to the maximum amount of scale 11.
• Holiday hours: 190,4 per year for fulltime and a possibility to save additional hours.
• Pension accrual with BeFrank, a modern, comprehensible and fairly priced pension.
• For >7 km each way, 100% reimbursement for public transport travel costs and, for private transport, €0.18 per km up to a maximum of 40 km each way.
• Do you prefer walking or cycling? Take advantage of our good bike scheme. Moreover, you will receive a reimbursement of €0.18 per km.

Watch this video with more information about joining Amsterdam UMC Research BV.

This 4 year ZonMW funded PhD position will be supervised by Prof. Noam Zelcer. This project is a close collaboration with Prof. Bart van de Sluis and Dr. Karin Wolters (UMC Groningen, The Netherlands), who also have a PhD position available. The Zelcer lab aims to elucidate the molecular regulation of lipid metabolism using a combination of cellular and experimental mouse models, and harnesses this knowledge to diagnose and treat cardiometabolic diseases, such as non-alcoholic fatty liver disease and atherosclerosis, and rare inherited lipid disorders like NPC and X-ALD. The Zelcer group is an international and dymanic research group that is embedded in the Department of Medical Biochemsitry of the Amsterdam UMC. More information about the group and our recent work can be found on Zelcer lab website.

Amsterdam UMC Research BV supports non-profit scientific research. In doing so, we provide researchers with everything they need to excel. Our principal investigators (PIs) and project leaders offer support in the field of project management, finance and human resources. In medical scientific research projects, legal support is also provided.

Watch the video to find out more.