Re-engineering toxins to look at the machinery of exocytosis

Synaptic vesicle exocytosis, which is a fundamental process to life, leads to neurotransmitter release at nerve terminals. Dysfunctional exocytosis has been associated with various conditions, including schizophrenia and Obsessive-Compulsive Disorder (OCD). SNARE proteins are the machinery that drives exocytosis, which makes them particularly good targets for studying what happens at the cell level using various standard and super-resolution microscopy techniques. While classical antibody-based approaches have been used to fluorescently label SNAREs for standard confocal microscopy, the inherent properties of antibodies impose limits on super-resolution microscopy techniques required for studying the SNAREs.
Meanwhile, Botulism Neurotoxins (BoNTs), also known as Botox, are among some of the lethal substances known to man. This toxicity is due to their natural ability to bind and specifically cleave SNARE proteins. This causes Botulism, a condition characterised by impairment of neurotransmission and paralysis.
Since BoNTs naturally bind and specifically target neuronal SNAREs, our research group has been looking to re-engineer BoNTs in a way that these may still bind while not cleaving their target SNAREs. This would allow for the use of BoNTs as highly specific, super-resolution compatible labelling agents which would help dissect the cell dynamics that drive exocytosis.