lines, we developed 2D developmental protocols to generate cortical neurons. We found epigenetic and transcriptomic changes between control and mutant lines with disease causing mutations across three stages of differentiation (Cuvertino et al 2025). However, the brain is a 3-dimensional organ with considerable complexity- just considering the cortex. Therefore, in this project we will refine our new 3D brain cortical organoid model, extending development to more mature stages. The student will combine transcriptomics, epigenomics and different modes of cell imaging to gain a detailed analysis of when critical changes occur in KS1 brain development, what the major changes are and which cells they affect. With the valuable input of our Case partner Bio-techne, we will be able to refine the information we obtain from organoids including identifying lineage and stage specific changes in organelle behaviour. Supported by already funded research identifying drug targets, ultimately this understanding will take us nearer to new targeted treatments for KS1 patients to relieve symptoms and one day fully alleviate disease.

lines, we developed 2D developmental protocols to generate cortical neurons. We found epigenetic and transcriptomic changes between control and mutant lines with disease causing mutations across three stages of differentiation (Cuvertino et al 2025). However, the brain is a 3-dimensional organ with considerable complexity- just considering the cortex. Therefore, in this project we will refine our new 3D brain cortical organoid model, extending development to more mature stages. The student will combine transcriptomics, epigenomics and different modes of cell imaging to gain a detailed analysis of when critical changes occur in KS1 brain development, what the major changes are and which cells they affect. With the valuable input of our Case partner Bio-techne, we will be able to refine the information we obtain from organoids including identifying lineage and stage specific changes in organelle behaviour. Supported by already funded research identifying drug targets, ultimately this understanding will take us nearer to new targeted treatments for KS1 patients to relieve symptoms and one day fully alleviate disease.