Heme Channel Found

Washington University scientists have discovered how the vital but vulnerable heme molecules is shuttled across cell membranes

By Diana Lutz


Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco
The cytochrome c protein (colored ribbons), holds in its embrace a heme group (white honeycomb) that in turn clasps an iron atom (orange ball). This molecule is essential to life and any chemical that interferes with its activity is lethal.
In some ways a cell in your body or an organelle in that cell is like an ancient walled town. Life inside either depends critically on the intelligence of the gatekeepers.


If too many barbarians sneak into town, the town may be put to the torch. And if the cellular gatekeepers can't control the flow of ions and molecules into and out of the cell, the cell may die.

Because of their importance, cellular gates, channels and transporters, are the targets of intense scientific interest.

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Washington University Magazine Feature

Professor Younan Xia investigates imaginative applications of nanotechnology, and he applies keen observations to a wide range of disciplines: from fuel cell development to medical imaging and orthopedics.

"Nothing is too small to know, and nothing is too big to attempt.” —Sir William Van Horne (circa 1900)

When Van Horne linked the two extremes of the size spectrum 100-plus years ago, he could not have envisioned how small the objects of scientific study would become nor how large society’s problems would be. Nonetheless, he provided a fitting motto for research being conducted today at Washington University. Within laboratories in Whitaker Hall, Younan Xia engineers the tiniest structures—down to one ten-thousandth the thickness of a human hair—as agents to address some of society’s biggest concerns. Xia says that, increasingly, “technological advances in many areas will rely on nanotechnology,” as the field of miniaturized particles and devices is known. He foresees essential applications in everything from electronics to medicine. For example, a future laptop computer may require no batteries, relying instead on an onboard fuel cell to generate power. Its only requirement would be “a small supply of methanol,” Xia says.

As a student, Xia’s first interest was engineering; however, he trained in chemistry. Coming to Washington University in 2007, he established wide-ranging collaborations and, in the process, combined the two fields to create tiny, effective agents of change. Now, as the James M. McKelvey Professor in the Department of Biomedical Engineering, he follows what he calls “simple ideas” to guide his work applying nanotechnology to clean energy production, imaging, and healing.

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Junk-food binge alters gut microbes in less than a day

Switching from a low-fat, plant-based diet to one high in fat and sugar alters the collection of microbes living in the gut in less than a day, with obesity-linked microbes suddenly thriving, according to new School of Medicine research.

The study was based on transplants of human intestinal microbes into germ-free mice.
Over time, mice that received the transplants, or humanized mice, on the junk-food diet became obese. Their weight gain was in lock step with dramatic shifts in the types of intestinal bacteria present compared to mice on a low-fat diet.

Using the latest DNA sequencing technology, the researchers found that mice on the high-fat, high-sugar diet had more microbes and microbial genes devoted to extracting calories from their "western" diet. These microbial genes were turned on when the mice were switched to the diet high in fat and sugar.

The study, published in Science Translational Medicine, documents the intimate relationship between diet and the dynamic variations in the community of intestinal microbes that can influence metabolism and weight.

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Recovery act funds new flu drug discovery center

School of Medicine scientists are investigating a new way to fight the flu.

Funding has been received largely through the American Recovery and Reinvestment Act (ARRA) to establish a drug discovery center that will look for compounds that enhance the body's natural virus-killing mechanisms to overcome the flu.

Each year, government agencies work with scientists to develop new flu vaccines to block large-scale flu outbreaks. The vaccines have to be modified yearly because flu viruses constantly change their basic components so the body's immune system can't recognize them.

But the researchers, headed by Michael J. Holtzman, M.D., believe they can identify drugs that enhance the body's resistance to a large range of respiratory viruses. That means these drugs could prevent or treat many different seasonal flu viruses and the 2009 H1N1 flu virus as well as the common cold and other respiratory viruses.

The ARRA provided nearly $2.5 million through the National Institute for Allergy and Infectious Diseases to support this research.

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Mutation linked to pediatric brain tumor may pave way for targeted treatment

School of Medicine researchers have linked mutations in a gene to a benign pediatric brain tumor, a finding that will help scientists seek drug treatments that block growth of the tumors.
"Now that we understand the signature mutation in these common pediatric tumors, we can think about designing treatments that alter the pathway that gene controls," said David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology. "That's important because right now we have few treatments tailored to this tumor type."
Gutmann normally studies the tumors, known as pilocytic astrocytomas, in the context of neurofibromatosis 1 (NF1), an inherited condition that is one of the most common tumor predisposition syndromes. But pilocytic astrocytomas also occur sporadically in patients who do not have the NF1 mutation at a rate of about two to three new cases per 100,000 children per year.
To learn whether either condition could shed light on the other, Gutmann's team performed detailed genetic and genomic analyses of tumor samples from 70 patients with sporadic pilocytic astrocytomas and nine patients with NF1. The results appeared in a recent issue of Neurology.
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