Biomedical Beat - A monthly digest of research news from NIGMS

IN THIS ISSUE . . .
June 21, 2005

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The National Institute of General Medical Sciences (NIGMS), one of the National Institutes of Health, supports all research featured in this digest. Although only the lead scientists are named, coworkers and other collaborators also contributed to the findings. Additional news items are posted at http://www.nigms.nih.gov/News/Results/.

Cool Image: Cells Frozen in Time

yeast cell buds before dividing into two
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The fledgling field of X-ray microscopy lets researchers look inside whole cells rapidly frozen to capture their actions at that very moment. Here, a yeast cell buds before dividing into two. Colors show different parts of the cell. Seeing whole cells frozen in time will help scientists observe cells' complex structures and follow how molecules move inside them. Courtesy of Carolyn Larabell, a cell biologist at the University of California, San Francisco, and the Lawrence Berkeley National Laboratory.
 

Genetic Variation Alters Response to Common Anti-Clotting Drug

Millions of people take the anti-clotting drug warfarin (Coumadin) to prevent harmful blood clotting after a heart attack, stroke, or major surgery. But the proper dose of warfarin can vary greatly and can be hard to predict. By looking at the genetic makeup of people taking warfarin, a team led by biochemist Allan Rettie of the University of Washington in Seattle showed that variations in a gene involved in blood clotting may explain why certain people require a lower or higher dose of the commonly prescribed anti-clotting drug. The finding ultimately could help doctors determine each patient's warfarin dose more quickly and precisely.

"This work is a very important discovery in medicine and clinical pharmacology. It not only gives us a better understanding of why people respond differently to warfarin doses, but more generally points to the importance of understanding how a person's genetic makeup can alter a medicine's pharmaceutical effect. This information may become a factor in determining the drug dose prescribed to an individual or group of individuals."

—Richard Okita, NIGMS program director in pharmacological and physiological sciences

Full story
Rettie home page
Paper Abstract (from the June 2, 2005, issue of The New England Journal of Medicine)

The Healing Power of Worms

The Healing Power of Worms
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Creatures that can restore themselves after being snipped into pieces are helping scientists learn how the body grows and heals. Developmental biologist Alejandro Sánchez Alvarado of the University of Utah School of Medicine recently used a gene-silencing technique called RNA interference to search for regeneration genes in tiny worms called planarians. Sánchez Alvarado and his team found 240 planarian genes that, when silenced, caused a physical defect in the worm's growth and regenerative ability. The researchers hope to figure out how these genes allow specialized cells within the worm to travel to a wounded site and "turn into" any of the 30 or so cell types needed to regenerate a mature worm. Although humans are only distantly related to planarians, we have many of the same genes, so the findings offer important insights for regenerating injured body parts in people.

Image caption: Even after planarians have been cut into many small pieces, each piece "knows how" to make a new worm of just the right size, with head up and tail down. Courtesy of Peter Reddien and Alejandro Sánchez Alvarado.

Full story
Sánchez Alvarado lab
The Worm Returns (Sánchez Alvarado Findings story) 
Paper Abstract (from the May 2005 issue of Developmental Cell)

Structure May Help Reverse Antibiotic Resistance

Structure of an ABC transporter from Salmonella typhimurium, a bacterium that causes food poisoning.
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Many disease-causing bacteria have become resistant to the antibiotics commonly used to treat them. Although bacteria evade antibiotics in many different ways, one of the most effective is to pump them out via a channel-shaped protein in their cell membranes called an ABC transporter. Through X-ray crystallography, molecular biologist Geoffrey Chang of the Scripps Research Institute determined the structure of one of these transporters and proposed a mechanism for how it works. This information could lead to new ways to fight antibiotic resistance as well as improve cancer therapies, since a closely related human transporter can lead to multiple drug resistance in cancer.
 
Image caption: Structure of an ABC transporter from Salmonella typhimurium, a bacterium that causes food poisoning. Human proteins closely related to this transporter lead to multiple drug resistance in cancer. Courtesy of Geoffrey Chang.
 
Full story
Chang home page
Paper Abstract (from the May 13, 2005, issue of Science)

Fruit Flies Shed Sound on Human Deafness

Fruit Flies
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Although often a pest in the kitchen, fruit flies may help us understand our own hearing. A team of researchers, led by biologists Daniel Eberl of the University of Iowa and Daniel Kiehart of Duke University, identified a genetic defect that leads to complete deafness in these winged creatures. The scientists tested a fruit fly's response to vibrating wings—comparable to a serenade by an interested mate. Flies lacking the myosin VIIA protein were completely deaf. Researchers know that this protein and the gene making it play a role in human deafness, but they're unsure exactly how. Thanks to the work in fruit flies, they now have a model system for studying the mechanisms of human hearing loss.  

Image caption: A male fruit fly (right) serenades a female (left) by vibrating an extended wing. Courtesy of Daniel Eberl.

Audio clip: The "love song" of a male fruit fly, recorded with a tiny microphone and amplified, contains both "pulse song" (the raspy sounds) and "sine song" (the faint moaning sounds). Courtesy of Daniel Eberl.

Full story
Kiehart home page
Kiehart lab page
Paper Abstract (from the May 10, 2005, issue of Current Biology)

This research also was supported by the National Institute on Deafness and Other Communication Disorders, part of NIH.