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Clarkson Researchers Study Venom From Poisonous Marine Snails For Promising New Drugs
[Photographs for newspaper use are available at http://www.clarkson.edu/news/photos/moczydlowski.jpg and http://www.clarkson.edu/news/photos/bingham.jpg.]
For centuries, cone shells have been treasured by collectors for their beautifully patterned shells. But these marine snails are also among the most poisonous and complex creatures on earth.
Over the last few decades, scientists have begun looking at the components of their deadly venom as promising sources for biomedical and pharmacological applications.
“Venom from snakes and scorpions are a rich source of toxins that have yielded important insights into human diseases such as hypertension and a variety of neurological conditions,” says Edward Moczydlowski, professor and chair of the Biology Department at Clarkson and a pioneer in the study of how channel proteins are sabotaged by naturally occurring neurotoxins, in particular, the molecular mechanisms by which cone snail toxins preferentially target different body tissues. “Venom from cone snails has a far greater number of compounds than can be found in snake venom.”
Research has also shown that cone shells have the world’s fastest mutating genes. The genes that code for their venom mutate at a rate five times greater than the highest rate estimated for mammalian genes. As a result, cone snails have developed many distinct venoms that have been optimized through evolution to target specific ion channels and receptors.
“The astonishing variety of different toxins produced by cone shells represents a cornucopia of new substances for pharmacologists and neuroscientists to test for new medicines and therapies,” added Moczydlowski. “And because they are highly selective, they are likely to yield effective drug therapies that display a lower incidence of side effects.”
In his laboratory, Moczydlowski and his research team are working with cone snails to identify and isolate peptides from the snail’s venom that might be useful in the development of new drugs. Moczydlowski’s laboratory is one of only a handful in the world currently working with this material. It is also the only laboratory with an active “milking” program, a process by which the venom from live snails is collected.
“There are two ways to collect venom,” said Clarkson Research Scientist Jon-Paul Bingham, who has been working with conopeptides for over a decade. “The first way is to kill the snails and work with dissected venom glands. The other way is to maintain a collection of live snails and extract the venom.
“The problem with the first way is that there are many compounds in the snails’ venom glands that are not actually injected into prey to paralyze and kill it. So you must sift through thousands of compounds that are unlikely to be useful. The problem with the second way is that while it is far more efficient, it is not easy to milk a highly poisonous snail.”
But Bingham is a pioneer in the extraction of venom from live snails. He is also an experienced shell collector who himself gathered the live laboratory specimens, conus purpurascens and conus pennaceus, while scuba diving and reef walking in Panama and Hawaii. The scientists also have a vast catalogue of species frozen to supplement ongoing research efforts.
Once enough venom has been extracted, it is subjected to chemical analysis. The sample is run through a complex machine that separates and screens for peptides and eventually produces an amino acid sequence of each compound. Promising compounds are then reproduced synthetically. Ultimately, Moczydlowski and Bingham are interested in establishing an independent biopharmaceutical company that could develop and test promising drugs and eventually bring them to market.
Edward Moczydlowski joined the Department of Biology at Clarkson as chair last fall. Before coming to Clarkson, he spent 17 years at Yale University in the Department of Pharmacology. He has received numerous professional awards and distinctions for his scholarship, including the Seale Scholars Award, 1985-88, and the American Heart Association’s Established Investigator Award, 1985-90. He also serves on the editorial board of Biophysical Journal. He received his doctorial degree in biology in 1980 from the University of California, San Diego.
His research has focused on the investigation of ion channel proteins in naturally occurring neurotoxins using a variety of molecular biological approaches and electrophysiological techniques including single-channel analysis, planar bilayer, and whole-cell and patch recording.
Early in his career, Moczydlowski collaborated with Balomero M. “Toto” Olivera, a scientist at the University of Utah and an expert in cone snail peptide research, on the mechanism of a class of paralytic toxins that had been isolated from one of the most dangerous cone snails, conus geographus. Their work on the mu-conotoxin GIIIA established the mechanism of GIIIA as a muscle-specific toxin and provided strong evidence that nerve and muscle sodium channels are distinct molecular entities, a novel concept at the time.
moczydlowski.jpg: Cone shells are prized for their beauty by shell collectors, but these marine snails are also among the most poisonous creatures on earth. Edward Moczydlowski, professor and chair of the Biology Department at Clarkson University, and a team of researchers are working with cone snails in the laboratory to identify and isolate peptides from the snail’s venom that might be useful in the development of new drugs.
bingham.jpg: Cone shells are prized for their beauty by shell collectors, but these marine snails are also among the most poisonous creatures on earth. Edward Moczydlowski, professor and chair of the Biology Department at Clarkson University, and a team of researchers are working with cone snails in the laboratory to identify and isolate peptides from the snail’s venom that might be useful in the development of new drugs. Here, Clarkson Research Scientist Jon-Paul Bingham coaxes out a live snail in order to carefully extract its venom for further study.