Congratulations to Ivo Lieberam and Andrew Lowe for receiving a Research Grant from the Medical Research Council (MRC), to develop an in vitro model of neuromuscular circuitry, to investigate the disease mechanism of Amyotrophic Lateral Sclerosis (ALS).
ALS, sometimes called Lou Gehrig's disease, is a rapidly progressive neurodegenerative disease that affects motor neurons, nerve cells in the brain and the spinal cord which connect the central nervous system to skeletal muscles.
The model proposed in this project will be based on sorted pluripotent stem cell (PSC)-derived motor neurons, astrocytes and myofibres, which will be co-cultured in a compartmentalized tissue culture device.
“We will use this system, with a specific focus on peripheral axonal and synaptic cellular pathology. To this end, we will equip human PSCs carrying disease-associated mutations in the genes SOD1, C9ORF72 or TDP43 with genetically encoded optogenetic actuators and optical probes which will allow us to stimulate the cells, read their electrical activity and trace cellular features with live imaging.”
The researchers will study the impact of different stimulation patterns, modifier genes, and small molecule compounds on early pathological processes, in particular abnormal neuromuscular synaptogenesis and defective axonal transport. Of particular interest are protective modifier genes and compounds which rescue the disease phenotype and pinpoint potential therapeutic pathways.