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Producing neurotoxins to study the nervous system

Neurological toxins occur throughout the natural world and vary greatly in their effect on humans. Researchers have developed a high-throughput microbiological system to produce various neurotoxins and test their effects on the nervous system.
Producing neurotoxins to study the nervous system
Marine cone snails, genus Conus, carry venom that consists of over 100 different neurotoxins per species. These neurotoxins also have an array of effects on their prey. A system that allows for easy production and purification of these toxins will help scientists to study their targets, most often the ion channels in nerve cells.

The EU-funded 'Functional characterization of neuroactive toxins using an engineered bacterial type-III secretion system' (CONOTOX) project created such a rapid neurotoxin production and purification system. Researchers are engineering a bacterium, Salmonella enterica, to secrete neurotoxins into their growing environment, where they can be easily purified and tested.

To achieve this, the group investigated ways to improve secretion in S. enterica. Using these results, they created a modified S. enterica strain with improved protein secretion (neurotoxins are peptides, or small proteins). This approach was tested with a model neurotoxin (tetanus toxin) and was shown to be an effective system for neurotoxin production.

Researchers will now use this system to produce Conus neurotoxins. They will create a DNA library of neurotoxin molecules, produce and purify the neurotoxin peptides, and screen them for their effect on ion channels in nerve cells.

Ion channel function is a crucial but poorly understood part of the vertebrate nervous system. CONOTOX will produce a large variety of neurotoxins that can be used to improve our understanding of ion channels and how they function.

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