Our vital organs are protected by specialized body barriers. Our oral mucosa functions as one of our major physical protective barriers between the oral environment and the systemic circulation to restrict the passage of daily life products such as toothpaste, mouth wash, and dental medical device leachables. However, components of some of these products do pass the oral mucosa barrier and enter the blood circulation, exerting systemic effects. They may subsequently reach vulnerable organs, such as the brain and cause harmful effects. The brain is protected with a second body barrier: the blood-brain-barrier (BBB), which is a highly selective semipermeable border of endothelial cells that prevents specific solutes in the circulating blood from entering the central nervous system (CNS). Taken together, substances exposed to the oral mucosa may result in adverse neuroinflammation, neuronal dysfunction, and eventually neurodegeneration if they “breach our body barriers”. Therefore, their strict neurotoxicity assessment is essential to determine safety for human exposure. Such hazard assessment requires human in vitro models which closely represent functional human body barriers, which are lacking to date.

The aim of this project is to develop the brain part of ‘’Body Barriers’’, the next generation ‘organ-on-chip’ (OoC) platform. Body Barriers will form an in vitro miniature industrial platform and is totally unique because it consists of the three stand-alone vascularized OoC models (mucosa-blood barrier, blood-brain-barrier, brain organoids) derived from human induced pluripotent stem cells (hiPSCs) and cultured under dynamic flow in vascularized microfluidics bioreactors. Using this multi-organ-on-chip platform (Body Barriers), cultured in a single vascularized bioreactor, we aim to measure alterations in blood-brain barrier function, brain inflammation, and neurodegeneration upon application of metal containing dental leachables.

In this project you will develop immune competent brain organoids, connect them to the BBB using various in vitro platforms and test the effect of mentioned compounds using these models. Next, you will link this platform to models of the oral mucosa (currently developed by the appointed PhD student on the project) to form the Body Barriers. You will investigate how leachables exert their effect using these in vitro models and determine their levels in Alzheimer patient material. Ultimately, we will translate our findings to the clinic.

We seek a highly motivated and enthusiastic researcher with:

• Finished PhD in a field related to neuroscience, immunology, tissue engineering and/or iPSC organoid culture;
• Experience with in vitro models using iPSC technology and gene editing (i.e. Crispr/Cas) is a must;
• Affinity for (neuro)immunology, neuroscience and cell biology;
• A flexible and pro-active attitude with team spirit, but a strong ability to work independently;
• A ‘can-do’ mentality, with patience and perseverance;
• Excellent communications skills in English, both written and verbal.

Hepatitis B vaccination is mandatory and will be provided by Amsterdam UMC.

The intended start date for the project is September 1st 2024.

• The position is for 2 years. We first offer a fixed term contract for 1 year, which under normal circumstances will be prolonged with 1 year. We also provide you with the opportunity to follow further training and development.
• Salary scale: 10 € 3.359,- tot € 5.292,- (based on a 36 hour week), depending on qualifications and experience.
• Additional benefits including an 8.3% end-of-year bonus and 8% holiday pay. Calculate your net salary here.
• Your pension is accrued at The Dutch Pension Fund for government and education employees (ABP). Amsterdam UMC contributes 70% of this scheme
• We reimburse 75% of your OV travel costs (commuting costs).

For more information about our employment conditions, please visit our website.

Amsterdam UMC

This joint project will be performed at Amsterdam UMC, primarily in the Neuro-immunology research group of prof.dr. Elga de Vries together with the group of prof.dr. Sue Gibbs; Immunology Amsterdam – Department of Molecular Cell Biology and Immunology (MCBI) (location VUmc; O|2 Building).

You will work in a team with young and enthusiastic researchers (around 30), who have expertise in iPSC models, immunology, biochemistry, cell biology, (clinical) neuroscience and neurological diseases. This collaborative project is funded by the Dutch Research Council (NWO-TTW) and is embedded in Amsterdam Neuroscience.