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Protein connections: A network to understand disease

In the 1990s, the notion of "six degrees of separation" emphasized human linkages that connected people around the world.

Now, the same concept provides clues to unraveling the mystery of how different mutations in different genes can cause diseases with very similar characteristics. In a paper in today's edition of the journal Cell, scientists from Baylor College of Medicine and Harvard Medical School describe a network of proteins that when perturbed by mutations can result in ataxias, characterized by loss of balance and coordination because of degeneration of specific nerve cells. The concept can be used to study many diseases.

"We study degenerative diseases," said Dr. Huda Zoghbi, professor of molecular and human genetics, neurology, neuroscience and pediatrics at BCM, a Howard Hughes Medical Institute investigator and senior author of the paper. "A gene is mutated, and a defective protein is made. We need to know what proteins interact with it, and then we study those interactions to learn how the mutant protein can damage the neuron (or nerve cell)."

"A cell makes tens of thousands of proteins, "said Zoghbi. "One protein interacts with many of them. How do you find all the proteins that are relevant?"

She and the paper's first author, Dr. Janghoo Lim, a postdoctoral trainee at BCM, decided instead to study all the proteins that, when mutated, cause similar clinical problems, in this case ataxias.

"Perhaps the disease happens when these mutant proteins interact with common partners," she said.

To answer that question, Lim began to identify protein partners in the Harvard laboratory of Dr. Marc Vidal, associate professor of genetics and faculty member of the Dana Farber Cancer Institute.

"On the one hand, you have patients with diseases, and those diseases look alike, like the ataxias," said Vidal. "We are in the business of understanding the wiring diagram of cells. In each cell, there are 20,000 to
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Source:Baylor College of Medicine


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