Diffuse midline glioma is an aggressive childhood brainstem tumor where treatment methods are lacking. Most of these gliomas have a characteristic mutation in histone H3 at lysine 27 (H3K27M) that leads to global hypomethylation and overexpression of neurodevelopmental genes. Our group has recently developed a human induced pluripotent stem cell (iPSC) model with an inducible H3.3K27M allele in the endogenous gene locus. Nevertheless, the precise mechanisms that regulate the transformation from healthy cell to tumor remain poorly understood. The goal of this PhD project is to (1) determine how closely the iPSC model mimics human neurodevelopment and tumorigenesis, and (2) use this model to explore fundamental questions about tumorigenesis. In particular, the PhD candidate will develop and use single-cell RNA-sequencing techniques to characterize the iPSC model under a range of conditions.

This project is an international collaboration with a team at the German Cancer Research Center in Heidelberg, where the student will spend the first six months of the position for training. The student will thereafter coordinate with the Heidelberg team from Utrecht. The position will ideally begin February 2025, but the date can be negotiated.

• You should be highly motivated, detail-oriented, and interested in developing projects independently within a supportive team.
• You will coordinate a multidisciplinary, international collaboration and spend six months abroad.
• Background knowledge of neurodevelopment, brain tumors, and/or iPSCs would be beneficial but not required.
• Experience with molecular biology and cell culture is ideal, as well as an interest in single-cell genomic techniques and analysis.

Contact
Due to the vacancy holder's holiday, we are currently unavailable by telephone.

The maximum salary for this position (36 - 36 hours) is € 3.824,00 gross per month based on full-time employment.

In addition, we offer an annual benefit of 8.3%, holiday allowance, travel expenses and career opportunities. The terms of employment are in accordance with the Cao University Medical Centers (UMC).

The Department of Translational Neuroscience is the preclinical department of the Division Neuroscience of the University Medical Center Utrecht. The research mission of the Department of Translational Neuroscience is to discover and delineate mechanisms and processes which are fundamental to the development of neural systems and to the control of behavior, and to translate these to pathogenesis and disease models. The unique advantage of this Department of Neuroscience is its embedding in the clinical environment of UMCU and its multidisciplinary character. The Department’s toolkit includes light sheet microscopy, optogenetics, electrophysiology, an own animal facility, viral vector generation and more.