Biomedical Beat - A monthly digest of research news from NIGMS

IN THIS ISSUE . . .
May 19, 2010

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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. To read additional news items, visit NIGMS News, Twitter or Facebook. To check out free NIGMS publications, go to the order form.

Cool Image: Inside the Nucleosome

Courtesy of Karolin Luger, Colorado State University.
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Like a strand of white pearls, DNA wraps around an assembly of special proteins called histones (colored) to form the nucleosome, a structure responsible for regulating genes and condensing DNA strands to fit into the cell's nucleus. Researchers once thought that nucleosomes regulated gene activity through their histone tails (dotted lines), but a recent study revealed that the structures' core also plays a role. This finding sheds light on how gene expression is regulated and how abnormal gene regulation can lead to cancer. Courtesy of Karolin Luger, Colorado State University.

Luger lab

Whole-Genome Sequencing Reveals Health Risks

In the future, doctors might use the entire genome sequence of their patients to improve medical care. Courtesy of NHGRI.
In the future, doctors might use the entire genome sequence of their patients to improve medical care. Courtesy of NHGRI.

Today, doctors occasionally test one or two genes of a patient to help diagnose or treat a disease. In the future, they might have access to more than 20,000 genes. A key question, though, is whether doctors will be able to use these entire genomes. One answer comes from a research team led by cardiologist Euan Ashley of the Stanford University School of Medicine. The team was the first to comprehensively analyze the entire genome of a healthy person—also one of the team's researchers—to predict his risk for diseases and atypical drug responses. The study advances the concept that whole-genome sequencing could one day play a clinical role.

This work also was supported by NIH's National Heart, Lung and Blood Institute; the National Human Genome Research Institute; and the National Library of Medicine.

Full story
Ashley profile
Article abstract (from the May 1 issue of Lancet)
More on personalized medicine

Anatomy of a Pincher

Dynamin structure shows how it functions in vesicle formation. Courtesy of Josh Chappie.
Dynamin structure shows how it functions in vesicle formation. Courtesy of Josh Chappie.
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When a molecule arrives at a cell's outer membrane, the membrane creates a pouch around it that protrudes inward. Directed by a protein called dynamin, the pouch then gets pinched off to form a vesicle that carries the molecule to the right place inside the cell. To better understand how dynamin performs its vital pouch-pinching role, a team led by cell biologist Sandra Schmid at The Scripps Research Institute determined its structure. The team proposes that a dynamin "collar" at the pouch's base twists ever tighter until the vesicle pops free. Because cells absorb many drugs through vesicles, the discovery could lead to new drug delivery methods.

This work also was supported by NIH's National Institute of Diabetes and Digestive and Kidney Diseases and its National Institute of Mental Health.

Full story
Schmid lab
Article abstract (from the April 28 online issue of Nature)

Detecting Drugs' Dangerous Actions

This network map shows molecular interactions (yellow) associated with a congenital condition that causes heart arrhythmias and the targets for drugs that alter these interactions (red and blue). Courtesy of Seth Berger.
This network map shows molecular interactions (yellow) associated with a congenital condition that causes heart arrhythmias and the targets for drugs that alter these interactions (red and blue). Courtesy of Seth Berger.
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Since the completion of the Human Genome Project, scientists have compiled vast amounts of data about our genes and the proteins they make. They know where genes are located, which mutations lead to disease and how proteins interact. Now, systems biologist Ravi Iyengar and his colleagues at the Mount Sinai School of Medicine have integrated all this information into a framework that helped them understand how drugs can produce a side effect similar to the arrhythmias seen in people with a congenital heart condition. This framework could be used to detect and predict other drugs' dangerous actions.

Full story
Iyengar lab
Article abstract (from the April 20 issue of Science Signaling)



Shared Ancestry Leads Scientists to Disease Genes

Humans and distantly related organisms, like plants, frogs and worms, have a common genetic ancestry. Courtesy of Peggy I. Wang.
Humans and distantly related organisms, like plants, frogs and worms, have a common genetic ancestry. Courtesy of Peggy I. Wang.
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Scientists led by Edward Marcotte and John Wallingford of the University of Texas at Austin studied distantly related organisms, like frogs and worms, to learn more about human genes, including ones involved in disease. Using information about which genes operate together as a team in these organisms, the researchers were able to identify similar gene teams in humans. The researchers then could figure out what some of these human genes do by looking at the known function of the other team members. The method is expected to uncover the functions of other human genes and to identify new targets for drug therapy.

Full story
Marcotte lab
Wallingford lab
Article abstract (from the April 6 issue of PNAS)