Biomedical Beat - A monthly digest of research news from NIGMS

IN THIS ISSUE . . .
November 15, 2005

Check out the new 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 https://public.govdelivery.com/accounts/USNIGMS/subscriber/new?topic_id=USNIGMS_3.

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: Natural Nanomachine in Action

The picture shows an amino acid (green) being delivered by transfer RNA (yellow) into a corridor (purple) in the ribosome.
High res. image (749 KB JPEG)
Using a supercomputer to simulate the movement of atoms in a ribosome, researchers looked into the core of this protein-making nanomachine and took snapshots. The picture shows an amino acid (green) being delivered by transfer RNA (yellow) into a corridor (purple) in the ribosome. In the corridor, a series of chemical reactions will string together amino acids to make a protein. The research project, which tracked the movement of more than 2.6 million atoms, was the largest computer simulation of a biological structure to date. The results shed light on the manufacturing of proteins and could aid the search for new antibiotics, which typically work by disabling the ribosomes of bacteria. Courtesy of Kevin Sanbonmatsu, a computational structural biologist at the Los Alamos National Laboratory.

Full story [Link no longer active]
Sanbonmatsu lab home page
Article abstract (from the November 1, 2005 issue of PNAS)

Rogue Protein Clumps Kill Brain Cells in Lou Gehrig’s Disease

Scientists have observed that a hallmark of many brain-wasting diseases is the presence of protein clumps inside brain cells. Among people with the devastating neurodegenerative disorder called amyotrophic lateral sclerosis, or Lou Gehrig’s disease, 10 percent have an inherited form that’s caused by an error in the gene SOD1. While researchers know that this genetic misstep causes cells to make SOD1 proteins that don’t fold properly and form clumps, no one has proven that the clumping of the proteins is what causes neuronal cell death associated with Lou Gehrig’s disease. Using time-lapse microscopy to watch living brain cells one at a time, molecular biologist Richard Morimoto of Northwestern University has revealed that only cells containing rogue SOD1 protein clumps died. This finding helps explain how the disease occurs and could point the way to new treatment approaches.

Full story
Morimoto lab
Article abstract (from the October 10, 2005 issue of the Journal of Cell Biology)

Computer Models Show Dengue Virus in Catch-22 for Survival

Many viruses exploit the human body’s immune system to increase their replication and infect more people. But this ability also may be the downfall of some viruses, according to new computer models developed by infectious disease scientists Derek Cummings and Donald Burke of the Johns Hopkins Bloomberg School of Public Health. The models simulate the dynamic role that a process called antibody-dependent enhancement plays in the spread of the dengue virus, which annually infects millions of people worldwide. In the simulation, antibody-dependent enhancement allowed the virus to grow faster in people who had been previously infected and as a result had partial immunity to the virus. But faster growth triggered a more lethal form of the disease that led to more deaths and ultimately the extinction of the virus. The models may apply to other diseases in which partial immunity increases viral replication and could help inform the design and development of effective dengue vaccines.

Full story
Burke home page(no longer available)
Article abstract (from the October 18, 2005, issue of PNAS)

Researchers Uncover New Role for DNA-Packaging Molecule

Caption: Each spot of this microarray grid represents Htz1 presence at a specific segment of DNA that governs the activity of nearby genes. Htz1 is highly present in red spots, while it has moderate and low presence in the yellow and green spots, respectively. Htz1 loss is associated with gene activation. Courtesy of Bradley Cairns.
High res. image (1.87 MB PNG)

Caption: Each spot of this microarray grid represents Htz1 presence at a specific segment of DNA that governs the activity of nearby genes. Htz1 is highly present in red spots, while it has moderate and low presence in the yellow and green spots, respectively. Htz1 loss is associated with gene activation. Courtesy of Bradley Cairns.

To understand why certain genes turn on or off in cancer cells, researchers must first figure out what’s happening inside normal cells. New findings from cancer biologist Bradley Cairns of the University of Utah offer some insight. The DNA in chromosomes is wrapped around cellular bobbins called nucleosomes, which package the genetic material into a compact form. While scientists knew that the components of the nucleosome could vary, they were unsure what effects these variations could have on gene activation. But then Cairns discovered a key switch in certain genes—a nucleosome component called Htz1. When present, Htz1 keeps nearby genes off or repressed. But when it’s ejected, the same genes turn on. The results show that this variation in the nucleosome does in fact make fundamental contributions to regulating gene activity.

Full story
Cairns home page (no longer available)
Article abstract (from the October 21, 2005, issue of Cell)

How Genes Affect Drug Responses: 5 Years of Discovery

Green shows transporter proteins embedded in cell membranes. Transporter proteins in the liver and kidney purge drugs and other chemicals from the body. Genetic variations in these proteins can change how a person responds to medications. Provided by Kathy Giacomini. Copyright 2003 National Academy of Sciences, U.S.A.
High res. image (238 KB JPEG)

Caption: Green shows transporter proteins embedded in cell membranes. Transporter proteins in the liver and kidney purge drugs and other chemicals from the body. Genetic variations in these proteins can change how a person responds to medications. Provided by Kathy Giacomini. Copyright 2003 National Academy of Sciences, U.S.A.

Medicines that work wonders for some people can be ineffective or even toxic to others. To understand how genetic variations affect the way a person responds to medicines and to help doctors prescribe the drugs and dosages that work best for each person, NIGMS led the creation of a nationwide NIH Pharmacogenetics Research Network in 2000. Scientists in the network have greatly advanced the understanding of genes and medications related to asthma, heart disease, depression, cancer, and other health disorders. Kathleen M. Giacomini, a pharmacologist at the University of California, San Francisco, uncovered more than a thousand variants in cellular “gatekeeper” molecules called transporters. She is now studying how these genetic variants affect people’s responses to the antidepressants Paxil® and Prozac®. Scott Weiss, a research physician at Brigham and Women's Hospital and Harvard Medical School, has identified and is developing prototype tests to detect gene variants that affect the way people respond to asthma medicines. More examples are available at the link below.

Full story
PGRN home page