Last year, Chapman's group identified the mechanism by which the toxin enters cells. Inside the cell, the toxin targets three key proteins, which are essential for mediating the release of chemical signals from neurons and that governs how messages are sent from brain to muscles.
"The toxins are smart," Chapman notes. "They know where to go" inside cells to do the most damage.
The newest work, says Chapman, helps give scientists an inside-the-cell view of the toxin at work. The toxin employs a four-step process - from cell entry to blocking the release of chemical messengers from nerve endings - and interfering with any of the steps in the process can inhibit the poison's toxic action.
"We can screen for (agents) to block any one of those steps," explains Chapman. "We could screen one million drugs at a time, and you can do all the screening using live cells."
The potential upshot of such a screening technology could be the development of drugs that act like a prophylactic to confer protection from botulinum poisoning.
The new tests, according to Chapman, can be conducted with ordinary lab equipment. It works by introducing into cells bioluminescent proteins whose glow is extinguished in the presence of the toxin. The tests are capable of detecting all seven variants of the poison.
Currently, the most sensitive and common test for toxin activity is exposing mice to an agent. The process takes time and many animals are used and die in the process.
The Wisconsin Alumni Research Foundation has patented the new botulinum toxin technology. In addition to Chapman and Dong, co-authors of the new PNAS paper include William H. Tepp and Eric A. Johnson, both of the U
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Contact: Edwin Chapman
chapman@physiology.wisc.edu
608-263-1762
University of Wisconsin-Madison
27-Sep-2004