PhD Project Proposal: Building a better brain

The 1.3 kg human brain has a striking macro-architecture; grey matter areas consisting of predominantly neuronal cell bodies and synapses are connected via white matter tracts composed of myelin-coated axons. The myelin sheath, produced by specialised glial cells, is essential for fast and efficient electrical signal transmission in the brain supporting brain development, learning, and cognitive function. Conversely, demyelination (loss of or damage to the myelin sheath) impairs signal conduction and underlies disorders such as multiple sclerosis, leading to progressive motor and sensory deficits.
To study myelination, demyelination and remyelination capacity, researchers rely on three main experimental systems: in vivo animal models, in vitro 2D cultures, and 3D brain systems such as organoids and spheroids. Stem cell–derived human neurons and glia (from induced pluripotent stem cells, hiPSCs) now offer human relevant platforms for modelling disease, yet current in vitro systems have not replicated the grey/white matter division and as a result, neuronal wiring and physiology in these models is inconsistent, disorganised and difficult to interpret.
This project proposes using bioengineered nano-patterned culture substrates to guide the growth of hiPSC-derived neurons and glia into structured in vitro models that mimic a basic in vivo CNS organisation. These simplified neuronal systems will allow improved investigation and characterisation of neuronal conduction, myelination, and human-relevant disease mechanisms relevant to demyelinating disorders such MS and AD, but more importantly, offer a robust, reproducible model for wider application.

Supervisory Team:
Primary: Euan Brown
Secondary: Nick Leslie