From deadly spiders to your pain medicine

Jun Hong Gui, a post-doctoral researcher in the School of Medicine, is testing 93 toxins found in Australian funnel-web spiders against human pain receptors.
Jun Hong Gui, a post-doctoral researcher in the School of Medicine, is testing 93 toxins found in Australian funnel-web spiders against human pain receptors. Photo by Carol Hsin.

Yale researchers are screening toxins in the venom from one of the world’s deadliest spiders for potential use in pain medication.

Jun Hong Gui, a post-doctoral researcher working in School of Medicine professor Michael Nitabach’s laboratory, will be testing the activity of 93 toxins found in the venom of the Australian funnel-web spider against a dozen pain receptors. Funding for the project came in May 2009 from the federal government’s $787 billion stimulus package, and testing is planned to begin this week on frog eggs, Gui said.

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Since Australian funnel-web spiders, whose venom is fatal to humans, cannot be imported to the United States, Nitabach said Gui will not harvest toxins directly from the spiders. Instead, Nitabach received the spider venom’s genetic information from collaborators in Australia and sent them to a biotechnology company that synthesized the sequences into DNA. Nitabach also had the sequences for human pain receptors synthesized into DNA. Gui then used the DNA coding for the receptors and the toxins as a template to synthesise corresponding RNA that can be injected into the eggs.

“We don’t have any spiders here [and] we don’t have any venom,” Nitabach said.

Because the 1,000 to 1,500 toxins in the spider’s venom can be organized into about 100 families, Nitabach said, Gui will only sample a representative toxin from each family. Pairs of synthesized toxin RNA and pain receptor RNA will be injected inside frog eggs, which induces the frog eggs to produce the toxins and pain receptors using instructions from the RNA.

Since each toxin must be tested individually against each pain receptor at least five times, Gui will be injecting over 5,000 frog eggs with genetic material over the course of the experiment. After he injects the frog eggs with the genetic material, Gui said he will wait about two days for the frog eggs to produce the toxins and pain receptors before he can screen them.

To test if the pain receptors are working, Gui assembled a machine in December to measure the receptors’ activity in the eggs. Because pain receptors are channels that allow charged particles to pass into the cell, thus generating an electric current, if little or no electric current is detected in the frog eggs, it means that the pain receptors may have been blocked by the toxin, Gui said.

Once Gui has found a possible toxin that could work as pain medication, he said he will test the toxin another five times to avoid error. If the toxin continues to produce the same results, it will be tested in mouse tissue and if successful again, in a mouse.

To gather the frog eggs, Gui will perform surgery on a frog’s belly. Each surgery, Gui said, will provide about 1,000 eggs. Because the frog must be anesthetized for the surgery and are sutured afterwards, the procedure is unlikely harm the frog, said School of Public Health professor Leonard Munstermann; Yale, he added, has stringent rules against animal cruelty.

Nitabach said he became interested in testing Australian funnel-web spider venom when he was testing the effect of toxins on flies.

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