University at Buffalo - The State University of New York

Published: November 18, 2004

By LOIS BAKER
Contributing Editor

Little Miss Muffet probably wouldn't sit on a tuffet in Frederick Sachs' lab, even if he had such a seat.

He keeps spiders there. Tarantulas, to be exact.

Elizabeth Mulé holds Rosie, the 30-year-old tarantula who is the pet in Fred Sachs’ UB lab. Elizabeth recently visited UB to learn more about Sachs’ research and attend a press conference announcing the receipt of a major grant from the Oishei Foundation.
PHOTO: JOHN DELLA CONTRADA

But Little Miss Elizabeth Mulé, a 10-year-old from New Orleans who raises tarantulas as a hobby, is happy to pull up a seat.

Elizabeth and her mother, Susan, recently visited Sachs' lab to learn more about the lab's research and to attend a press conference announcing a $900,000 grant from the Oishei Foundation to advance Sachs' findings from the lab to the clinic.

Elizabeth struck up a long-distance friendship with the UB scientist when she learned of his research while searching the Internet for treatments for her father's congestive heart failure. Sachs and colleagues in UB's Center for Single Cell Biophysics have discovered a peptide in the venom of the Chilean Rose tarantula that shows promise as a treatment for several chronic diseases, one of which is congestive heart failure.

The Nov. 4 press conference at UB wasn't Elizabeth's first go-around with the media. She's already a media star, having appeared with Oprah, Jay Leno and Ellen DeGeneres. But meeting Sachs and his co-investigators was different.

"Elizabeth can hold her own with Leno or Oprah any day," said Susan Rule. "But she was nervous about coming to UB. These scientists are her heroes."

The peptide that Sachs and his UB colleagues have isolated from tarantula venom shows promise as a therapy not only for congestive heart failure, but also for conditions as disparate as muscular dystrophy and urinary incontinence.

The researchers discovered the peptide, purified it and changed its structure to its mirror image to prevent it from being destroyed by stomach enzymes or the immune system. Their most recent research results were published in July in the journal Nature. Earlier findings were published in Nature and the Journal of General Physiology. They now will study ways to turn the peptide into treatments for specific disorders with the aid of the Oishei grant.

"These funds will help us identify the key components of the peptide's molecular structure and learn how it works to block mechanical transduction in cells," said Sachs, a professor of biophysics and lead researcher on the work. "We expect the results will accelerate the path leading to clinical applications."

Co-investigators Tom Suchyna, research associate, and Philip Gottlieb, associate professor of physiology and biophysics, play pivotal roles in the research.

Thomas E. Baker, president of the John R. Oishei Foundation, said Sachs' work advances the foundation's interest in supporting translational research for common illnesses.

"We believe the best role we can play is to move excellent, promising new approaches from the lab to the clinic," he said. "We also believe we can provide the boost of extra time that researchers like Dr. Sachs need to establish a case for new support from the federal level."

The novel peptide from tarantula venom, labeled GsMTx4, is the only agent known to specifically block pores in cell membranes called mechanosensitive ion channels. "These are the transducers that turn mechanical stress into cellular signals," said Sachs. "They are familiar to us as the sensors for hearing and touch. However, they also have been implicated in biological functions as diverse as muscle coordination, blood pressure and volume regulation.

"Stretch-sensitive channels probably are involved in many normal tissue functions that involve changes in mechanical stress, such as bladder filling, heart and circulatory-system responses to changes in blood pressure, and fluid balance," he said. "They also are involved in pathologies such as cardiac arrhythmias, congestive heart failure, the elevated calcium levels in muscular dystrophy and the growth of brain tumors."

Researchers in Sachs' laboratory discovered these channels nearly 20 years ago and since then have been focusing on their properties. It was difficult to associate the channels with particular physiological functions before the discovery of GsMTx4, said Sachs, because there were no compounds the channels responded to specifically.

"Basically, we went on a fishing expedition looking for a compound, screening chemicals we thought might work. Eventually, we started looking at the venom of poisonous bugs. We didn't know why a bug would possibly make such a thing, but thought it was worth a try."

The venom of two spiders, as it turned out, did act on the channels. One was a type of tarantula commonly known as the Chilean Rose, which became the focus of their work.

"Rosie," a Chilean Rose tarantula that measures nearly six inches tip-to-hairy-leg-tip and is thought to be 30 years old, is now the laboratory pet. Several younger members of her species also live in the laboratory and are used for various aspects of the research.

In addition to the Oishei Foundation, Sachs' laboratory has been funded by the National Institutes of Health, the United States Army Research Office and NPS Pharmaceuticals, Inc.