2A. Novel in vitro human models to investigate brain development and cancer
Our laboratory has recently optimized various culture methods to generated human brain organoids models that more closely resemble the developing of the human brain. In parallel, we have also implemented various genome editing strategies in these models that allows to introduce specific gene mutations and also to specifically label cell populations, so to be able to trace them and study their behaviour.
These models offer the unique opportunity to be developed into platforms to study mechanisms of cancer initiation both from a molecular and a cellular prospective. In the current project the PhD student will be involved on the one hand on study the effect of introducing defined mutations found in different subtypes of (childhood) pediatric cancer, in a developmental time- and cell- specific manner. On the other hand, the project aims at establishing robust models of tumor tissue-generated brain cancer organoids which can be engineered to reveal and study cellular heterogenous behaviour in real-time.
This project will employ, amongst other techniques, the use of human brain organoids, CRISPR-Cas9 editing and gene tagging tools, live imaging and sequencing tools such as single cell sequencing, and overall aims at generating novel and powerful human models to better dissect molecular determinants and different cellular contribution in brain cancer.
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