Project Title: Establishing motor neurons derived from induced pluripotent stem cells as a model to investigate the neurotoxic activity of medically important presynaptic snake neurotoxins and novel inhibitory therapeutics for snakebite.
Project Summary: Snake venoms are a cocktail of multiple toxins that often cause a life-threatening emergency once a victim is bitten. One of the most medically important classes of toxins are the presynaptic phospholipase A2 neurotoxins (SPANs), which destroy the presynaptic terminal of the neuromuscular junction through a complex, yet largely undefined, mechanism. This project will establish whether motor neurons generated from induced pluripotent stem cells that are routinely used to investigate neurodegenerative diseases can serve as an alternative model to investigate SPANs, enabling elucidation of their mechanism of action and facilitating the discovery of more effective snakebite therapeutics against presynaptic neurotoxins.
