IN THIS ISSUE . . .
March 21, 2006

• Cool Image: Beaded Bacteriophage
• Computer Models Could Speed Drug Discovery
• Common Mechanism May Underlie Neurodegenerative Diseases
• Cracking Open an Anti-Cocaine Molecule
• Profiles in Discovery: Proteins and Viruses

Check out the Biomedical Beat Cool Image Gallery.

Got research news to share? E-mail us at info@nigms.nih.gov.

To change your subscription options or unsubscribe, visit the Biomedical Beat subscription page on the NIH LISTSERV Web site.

Subscribe to the RSS version of Biomedical Beat by selecting this XML link and following your news reader's instructions for adding a feed.

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. To read additional news items, visit NIGMS News.

Cool Image: Beaded Bacteriophage

High res. image (1.36 MB JPEG)

This sculpture made of purple and clear glass beads depicts bacteriophage φX174, a virus that infects bacteria. It rests on a surface that portrays an adaptive landscape, a conceptual visualization. The ridges represent the gene combinations associated with the greatest fitness levels of the virus, as measured by how quickly the virus can reproduce itself. φX174 is an important model system for studies of viral evolution because its genome can readily be sequenced as it evolves under defined laboratory conditions. Courtesy of Holly Wichman, an evolutionary biologist at the University of Idaho. (Sculpture by Wichman; surface by A. Johnston, an undergraduate student in landscape architecture; and photo by J. Palmersheim.)

Wichman lab home page

Computer Models Could Speed Drug Discovery

High res. image (141 KB GIF)

Predicted structure of a receptor for dopamine, a neurotransmitter. Courtesy of Jeffrey Skolnick, Yang Zhang, and Mark Devries.

A team led by systems biologist Jeffrey Skolnick of the Georgia Institute of Technology has created computer models of more than 900 cell receptors from a class of proteins targeted by many drugs. Because these G protein-coupled receptors tend to fall apart outside their cellular environment, researchers have determined very few of their structures experimentally. While the computer-generated structures don’t capture all the details of the actual receptors, the models may speed drug discovery by helping researchers study how different compounds interact with cellular targets.

Full story
Skolnick home page
Article abstract (from the February 17, 2006, issue of PLoS Computational Biology)

Common Mechanism May Underlie Neurodegenerative Diseases

High res. image (68 KB JPEG)

C. elegans worm expressing a protein prone to clumping that fluoresces green (right), and a related protein that does not clump (left).

Clumps of misfolded and damaged proteins that destroy brain cells are a hallmark of neurodegenerative diseases. But explanations for what causes cell death in Alzheimer’s, Parkinson’s, Huntington’s, and other diseases vary widely, leading scientists to question the connection among the brain disorders. A new study led by cell biologist Richard Morimoto of Northwestern University offers evidence that a common mechanism may underlie these diseases. When the research team introduced a protein prone to clumping into the roundworm C. elegans, they found that unrelated, semi-stable proteins in the cells lost their ability to fold and, as a result, function properly. The researchers suggest that this loss of function would interfere with many cellular processes, possibly explaining the cell damage and death associated with neurodegenerative diseases.

Full story
Morimoto Lab home page
Article abstract (from the February 9, 2006, issue of Science)

Cracking Open an Anti-Cocaine Molecule

High res. image (144 KB JPEG)

Close-up of an antibody molecule (light blue surface) bound to cocaine (colored sticks). Courtesy of Ian Wilson and Xueyong Zhu. This work was co-funded by the National Institute on Drug Abuse at NIH.

Cocaine abuse remains a major public health problem. While no effective medication exists to treat cocaine addiction and overdose, some molecules have shown promise in animal studies. A research team led by structural biologist Ian Wilson of the Scripps Research Institute has now revealed the inner workings of one such molecule—an antibody designed in the laboratory to quickly sop up and destroy cocaine before it reaches the brain. The scientists used X-ray crystallography to visualize molecular snapshots of the antibody in action. The study reveals specific ways to modify the antibody molecule to make it degrade cocaine more efficiently. The eventual goal is to design a medication to safely and effectively treat cocaine abuse.

Full story
Wilson lab home page
Article abstract (from the February 2006 issue of Structure)

Profiles in Discovery: Proteins and Viruses

The quest for new knowledge to improve health involves thousands of NIGMS-funded scientists working at the cutting edge of biomedical research. Among them is chemical biologist Neil Kelleher of the University of Illinois in Urbana-Champaign, who uses an enormous magnet and sophisticated computer tools to analyze proteins. Read about his work in “The Humpty Dumpty Dilemma,” appearing in the March 2006 issue of Findings. In the same issue, go on “Viral Voyages” with structural biologist Mavis Agbandje-McKenna, who began life in a war-torn Nigerian village. Now at the University of Florida, she studies how harmless viruses can turn deadly with just a few genetic changes.

The Humpty Dumpty Dilemma
Viral Voyages
Kelleher home page
Agbandje-McKenna home page
Findings home page