Creating Clinically Relevant Novel 3-Dimensional Neuronal-Glial Cell Models for Understanding the Molecular Pathology of Multiple System Atrophy’s Neurodegeneration

About the Project

Multiple System Atrophy (MSA) is a rare, progressive neurological disorder that is without cure, that causes nerve cell loss in the brain, leading to issues with movement, balance, blood pressure, bladder control, and digestion, as the autonomic system is also affected. During MSA, select cell types within specific brain regions progressively degenerate. In MSA-susceptible neurons and in glial oligodendrocytes there is buildup of α-synuclein (αSyn) protein aggregates, spreading cell-to-cell. This self-funded PhD project will make use of human adult-derived iPSC (Induced Pluripotent Stem Cells) cells, that will be chemically reprogrammed to turn their neurochemical identities into specific cell types associates with particular neurotransmitters. These will be co-cultured with stem-cell like oligodendrocytes, and applying αSyn protein aggregates engineered from recombinant protein.

Furthermore, to better reflect the brain environment, scaffolding systems will be tested and optimised, to bet support culturing of the cell system in a 3-dimensional format. The experimental platform will then be used to assess for neuronal excitability, cytotoxicity/-stress markers & cholinergic metabolome/cytokine profiles in cell culture lysates/supernatants. The data will instigate future work to directly benefit MSA patients via improved differential diagnostics & treatments, whilst serving as training for a PhD student in various state-of-the-art clinically translational methods.

To apply, please contact Dr Ilse Pienaar at i.pienaar@bham.ac.uk.