Molecular Horizons - Michelle Newbery, PhD Exit Seminar

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by motor neuron degeneration and muscle wasting. There is currently no effective treatment or cure for ALS and therefore further research into the disease progression is required. The majority of ALS research focuses on motor neurons however, the impact of ALS on skeletal muscle gene expression and function is less well understood. Induced pluripotent stem cells (iPSCs) provide the unique opportunity to differentiate patient derived cells into skeletal muscle and motor neurons, to study the cell types affected in ALS in a dish. Myogenic precursors, myoblasts and myocytes differentiated from ALS and control iPSC lines were analysed by RNA sequencing to determine differences in gene expression in ALS skeletal muscle cells during differentiation. ALS skeletal muscle cells were found to have significant changes in RNA expression levels at all stages of skeletal muscle differentiation. In addition, iPSC derived skeletal muscle cells and motor neurons were co-cultured to form neuromuscular junctions (NMJs) and were used to assess NMJ function in a dish. This model was also used to test mitochondrial transfer, a potential ALS therapeutic strategy.