Biomedical Beat - A monthly digest of research news from NIGMS

IN THIS ISSUE . . .
August 16, 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. To read additional news items, visit NIGMS Research Around the Nation.

Cool Image: Statistical Cartography

Statistical Cartography
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Like a world of its own, this sphere represents all the known chemical reactions in the E. coli bacterium. The colorful circles on the surface symbolize sets of densely interconnected reactions. The lines between the circles show additional connecting reactions. The shapes inside the circles are landmark molecules, like capital cities on a map, that either act as hubs for many groups of reactions, are highly conserved among species, or both. Molecules that connect far-flung reactions on the sphere are much more conserved during evolution than molecules that connect reactions within a single circle. This statistical cartography could reveal insights about other complex systems, such as protein interactions and gene regulation networks. Courtesy of Luis A. Nunes Amaral, a chemical and biological engineer at Northwestern University

Amaral home page

Nanoparticle Zaps Cancer with One-Two Punch

Chemotherapy-loaded nanoparticles (left) form the core of the nanocell (right). Courtesy of the Sasisekharan lab.
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Caption: Chemotherapy-loaded nanoparticles (left) form the core of the nanocell (right). Courtesy of the Sasisekharan lab.

The latest molecular weapon in the fight against cancer is so tiny that 20,000 of them would fit on top of a pinhead. Designed by biological engineer Ram Sasisekharan of the Massachusetts Institute of Technology, this infinitesimal tool delivers two different medicines, making it extra powerful at killing tumors. First, the structure sneaks into the leaky blood vessels that feed cancer cells and then releases a drug from its outer membrane that shuts off the tumor’s blood supply. Next, the device dumps a strong dose of chemotherapy that knocks out the cancer cell. The technique is promising in mice, but it awaits human testing.

"Utilizing his expertise in engineering and basic biology, Dr. Sasisekharan has created a powerful new way to deliver drugs inside tumors."

—Pamela Marino, NIGMS program director in pharmacological and physiological sciences

Full story
Sasisekharan lab
Article abstract (from the July 28, 2005 issue of Nature)

Fat Molecules Help Proteins Fold

In origami, how you fold the paper determines what you create. Similarly, the folding of proteins inside our bodies makes all the difference between health and disease. Scientists have long thought that a protein's chemical sequence—and often, the assistance of helper molecules—guarantees proper shape. But now it appears that fat molecules (lipids) also aid the folding of membrane proteins, according to findings from biochemist William Dowhan of the University of Texas Medical School at Houston. Membrane proteins control the communication and flow of materials in and out of cells and are the target of many medications. Understanding how membrane proteins fold could help scientists address a host of diseases caused by improperly folded proteins, including Alzheimer's, Parkinson's, cystic fibrosis, and certain forms of cancer.

Full story
Dowhan home page
Article abstract (from the July 15, 2005, issue of the Journal of Biological Chemistry)

Researchers Model Avian Flu Outbreak

Model of an uncontrolled outbreak of avian flu in Thailand. Red shows new cases while green shows areas where the epidemic has finished. Courtesy of Neil Ferguson.
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Caption: Model of an uncontrolled outbreak of avian flu in Thailand. Red shows new cases while green shows areas where the epidemic has finished. Courtesy of Neil Ferguson.

Scientists fear that the deadly H5N1 strain of the avian flu virus could soon start passing efficiently between people. To better understand what could happen if such an event occurs, two research groups led by computational biologist Neil Ferguson of Imperial College in London and by biostatistician Ira Longini, Jr., of Emory University developed computational models of a hypothetical H5N1-based outbreak in Southeast Asia. Although the models differ, their general conclusions were similar. Preventing a pandemic would require a combination of carefully implemented public health measures, such as targeted distribution of antiviral medication and quarantine, introduced soon after the first cases appear. The models offer tools that policymakers and others could use to better understand and respond to actual outbreaks.

Full story
Ferguson home page
Longini home page
Modeling infectious diseases
Article abstract (from the August 3, 2005, issue of Nature)
Article abstract (from the August 5, 2005, issue of Science)

Protein Lends a Hand in Cell Movement

Vinculin before structural changes. Vinculin after structural changes.
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Caption: Vinculin before (left) and after (right) structural changes. Courtesy of Tina Izard.

Like choreographed dancers, our cells move in a coordinated manner to help tissues form during embryonic development and to help our bodies fight infection. But this directed movement, in which proteins at the surface of a cell latch onto other molecules to pull the cell along, requires many modifications in the cell’s physical structure. New studies led by cell biologist Tina Izard of St. Jude Children's Research Hospital in Memphis show that a protein called vinculin undergoes dramatic structural changes that allow it to bind to other molecules involved in cell migration and to reinforce the cell's skeleton. Knowing more about the complex steps that regulate cell movement could advance our understanding of development, the distribution of immune cells, and the spread of cancer.

Full story
Izard home page
Article abstract (from the July 15, 2005, issue of Molecular and Cellular Biology)