Creating neurological disorder in the dish: deriving the building blocks and developing the infrastructure

GM D'Abaco1,2, C Mattei1,2, AJ Alshawaf1,3, B Nasr1,2, G Chana1,2,3, E Skafidas1,2,3 and M Dottori1,2

  1. Centre for Neural Engineering, Melbourne School of Engineering, The University of Melbourne
  2. Department of Psychiatry, Royal Melbourne Hospital, The University of Melbourne

There is an imperative to develop relevant cellular systems that faithfully model normal brain development and neurological disorders. The use of hESCs as a cell culture model is well established and validated as a dynamic tool to study the CNS. However the study of neurological disorders has been impeded by a lack of access to cells that underlie disease development. To this end, induced Pluripotent Stem Cells (iPSCs) represent an extension of the hESC modelling system which, together provide an opportunity to investigate and model human brain development and disorders. An important objective in the field of neuroscience research is to understand the molecular cues that regulate synaptogenesis and the formation of cortical neural networks. The cerebral cortex in mostly composed of glutamatergic and inhibitory neurons which together, regulate synaptogenesis and the formation of neural networks. A disruption of such networks may represent an aetiological factor in the development of neurological disorders. A major focus of our ongoing is the purification of cortical neurons and developing systems for interrogating synaptogenesis and neural network formation with the specific focus of establishing 3D cell culture systems that model normal neuronal homeostasis and functionality more faithfully. This will be crucial in the understanding of neurological disorders that could additionally inform and better validate therapeutic target strategies for disease amelioration. Toward this overall aim, we are investigating the use of graphene foam-a conductive substrate, as a potential basis for culturing neuronal cells in 3D.