The Sting

01.05.1998

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Targeting nerve cells

 

Caveat: Don't be taken in by size. That's the rather pointed message delivered courtesy of the cone snail. Though small, its venom has a deadly, zooming-in quality that makes these creatures especially noxious. Dr. Michael Fainzilber of the Biological Chemistry Department is part of the effort to turn these killers into healers.

"My uncle told me never to touch cone snails when I was a child, so I'd pick them up carefully and collect them," he recalls.

Fainzilber's childhood interests in Africa carried into adulthood in Israel, and into an important discovery: He has uncovered one of the cone snails' paralyzing, lethal proteins and followed its deadly sequence of destruction. These proteins are unique in their specificity. Specialists in pharmacology and biomedicine are taking note, as specificity is the name of their game.
 
Many of the Institute's scientists wend their way to Israel in an intriguing fashion; Fainzilber's story is especially captivating. Born in Tanzania, then a British colony to which Holocaust refugees were sent, he'd go swimming in the waters off its eastern coast in search of interesting shells.

Faintly conscious of a land called Israel, to which his father had been refused entry by the British after fleeing Europe, he did not feel like the son of outcasts. Tanzania, after all, was so rich in the natural treasures which feed a child's curiosity. "We had lions near our backyard," he says.

The world's troubles would soon have an effect on his life as well. Independence in Tanzania in 1961 led to a shift towards communism. One day in 1972, Fainzilber's parents told him that they were all going off on a "holiday." Their destination was Israel, by then independent for almost 25 years. Luckily for the 10­year­old Fainzilber, they settled in Haifa, the main port city of Israel ­ where he could keep up his snorkeling.

Since that time, one could say he's been "snorkeling his way" to the Weizmann Institute. When asked to name the oceans or seas in which he hasn't gone diving, Fainzilber is stumped. More than just a pastime, his diving has meshed with his scientific work, bringing him to the Weizmann Institute this past year.

With the help of his friends at the Free University of Amsterdam and UC San Francisco, Fainzilber has already discovered one paralyzing protein in the snail's venom and sequenced it. What this toxic protein does is latch on to a very specific site on the nerve cell of its prey, pulling open one of its channels. The channels, situated on the cell membrane, act as "doors" to the cell, letting particles in only at the turn of a "key." The key opening this particular channel is normally a specific combination of four neuropeptides.

This toxic protein dodges the channel's four-peptide "combination-lock" and opens the channel to streams of ion particles. The cell's innards become a free-for-all, the ion inflow unregulated. Since ion particles set off a signal instructing muscle contraction, the result of their unregulated flow is constant muscle contraction ­ in other words, paralysis.

The scientific importance of Fainzilber's discovery may lie in the special features of its target. "The channel targeted by the toxin is a pacemaker channel, meaning it regulates rhythmic processes," says Dr. Fainzilber. "The challenge now is to find similar toxins that could target other pacemaking channels, for example, in the heart. Then we may be able to engineer them to do something useful. One could call it an effort to turn swords into plowshares."
 

Stinging cone snails

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