Diffuse intrinsic pontine glioma (DIPG) is the most aggressive childhood brain cancer with no effective treatment. New avant-garde approaches are now critical to understand the basic science of how DIPG functions and determine new ways to therapeutically treat it. However, progress is difficult due to the rarity of tissue. Using an exclusive DIPG tumour resource, we will apply a contemporary in vitro neural engineering technology that permits one to map the communication within organised grid networks of cells from the single-cell level through to large network scales on a chip. With this technology, we will build a ‘perineuronal satellitosis’ model, particular to DIPG, and determine the roles that calcium receptors and pathways play in reducing cell growth and inducing cell death. Using clinically available inhibitors and validating with animal models, we will identify key calcium signalling modulators, offering new treatment options that can be subsequently translated in children diagnosed with DIPG.