IN THIS ISSUE . . .
February 22, 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.
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Cool Image: Movements of Myosin
Inside the fertilized egg cell of a fruit fly, we see a type of myosin, related to the protein that helps our muscles contract, made to glow by attaching a fluorescent protein. At the start of the movie, the myosin proteins are distributed relatively evenly near the surface of the embryo. The proteins temporarily vanish each time the cell's nuclei--at this point buried deep in the cytoplasm--divide. When the multiplying nuclei move to the surface, they shift the myosin, producing darkened holes. The glowing myosin proteins then gather, contract, and start separating the nuclei into their own compartments. Courtesy of Victoria Foe, research professor at the Center for Cell Dynamics, University of Washington's Friday Harbor Laboratories.
Time-lapse movie (no longer available) (20.9MB MOV)
Foe home page (no longer available)
Center for Cell Dynamics home page
Antidepressants for Hot Flashes May Interfere with Tamoxifen
Women with breast cancer often take the drug tamoxifen to treat the cancer and antidepressants to ease the depression and hot flashes--side effects of the cancer drug. However, a study led by David Flockhart, a clinical pharmacologist at the Indiana University School of Medicine in Indianapolis and a member of the NIH Pharmacogenetics Research Network, shows that a common class of antidepressants called selective serotonin reuptake inhibitors can hinder the effectiveness of tamoxifen. The findings also point to genetic differences that may explain why tamoxifen works well in some women and not others, and why some people respond better to certain antidepressants. The new information could help doctors make more informed choices about what drugs are likely to work best for different patients.
"What this study tells us is that genetic differences matter for drug responses. From these results, researchers can begin to make predictions and share this knowledge with physicians, who can then prescribe the right combination of drugs the first time, rather than needing to take a one-size-fits-all approach. Thus, patients should be able to avoid unpleasant side effects, or worse, taking drugs that offer them no benefit at all," said Rochelle M. Long, chief of the Pharmacological and Physiological Sciences Branch at NIGMS and program director for the Pharmacogenetics Research Network.
Full story (no longer available)
Flockhart home page
The Shapes of Life
Crystal structure of a protein with unknown function from Leishmania major, a parasite of the human immune system.
Proteins come in all sorts of different shapes that allow them to do their many jobs in the body. We now know the structures of an additional 1,000 proteins, thanks to a national program called the NIGMS Protein Structure Initiative that has focused on developing the methods and technology to make protein structure determination faster, cheaper, and more reliable. This structural information will shed light on how proteins function in many life processes and could lead to targets for the development of new medicines.
Full story (includes links to a protein structure slide show and high-res image gallery, as well as questions and answers about the NIGMS Protein Structure Initiative)
PSI home page
Scientists Uncover Cellular Process Involved in Heart Development
As the juvenile heart develops into an adult heart capable of increased workloads, it changes structurally. A research team led by Xiang-Dong Fu, a cell biologist at the University of California, San Diego School of Medicine, has identified a protein involved in this transition. The protein, called ASF/SF2, is part of a cellular process called alternative splicing, which allows a single gene to produce different but related proteins. Fu's studies show that mice born with mutated or absent ASF/SF2 produce the wrong version of a key protein at the juvenile-to-adult transition and die as they near adulthood. This discovery may help scientists better understand heart physiology during development and may provide insight into factors that contribute to heart attacks.
Image caption: The top images are cross sections of the heart from a normal mouse (left) and from a mouse lacking ASF/SF2 (right). The image on the right shows enlargement of the left (st1:City w:st="on">LV) and right (RV) ventricles and thinning of the septum (S) between them. The bottom images represent spontaneous calcium leakage in normal (left) and ASF/SF2-lacking (right) heart cells. Increased leakage indicates a defect in calcium handling, a critical component of heart cell contraction and cardiac function.o:p>
High-res image (1.85MB JPG)
Fu home page
Vaccinating More Kids Could Slow Flu Transmission
When it comes to the flu, the best way to prevent illnesses and deaths might be vaccinating more children, according to mathematical models developed by biostatisticians Ira Longini and Elizabeth Halloran at Emory University Health Sciences Center. The models show that vaccinating 70 percent of school children, even if they're considered at low risk of flu complications, would drop community-wide flu transmission to very low levels. Giving the vaccine to only 50 percent of the children also would significantly reduce infection. Although this vaccine strategy needs to be evaluated more carefully, the researchers say it offers a possible alternative for controlling influenza, especially when the vaccine supply is limited.
"Although research on computational models is in its infancy, it does show that models can be very valuable tools, especially when it comes to understanding the spread of disease. This work by the Emory group shows that large-scale computing can provide policymakers with additional information that can aid them in their decision-making processes," said Irene Eckstrand, NIGMS program director for the Models of Infectious Disease Agent Study, which develops computer simulations to better understand disease outbreaks and test different strategies for containing infection.
Full Story (no longer available)
Halloran home page
Longini home page
New Tool Spies on Interacting Proteins
A protein's life inside the cell is anything but lonely--dynamic interactions among millions of proteins take place constantly. To spy on these interactions, computational biologist Robert Murphy of Carnegie Mellon University has recently invented a computerized tool that can locate proteins clustered in the same place in a cell. The tool scans thousands of microscopic images of fluorescently tagged cell proteins, looking for signature features, such as shape, texture, and edge qualities. Murphy's method is a big improvement on current approaches because it doesn't rely on interpretation by the human eye. The approach could help scientists identify what enables proteins to gather in one part of the cell--information critical for foiling a disease like cancer.
Image caption: Murphy's computerized tool scans thousands of fluorescent cell images to find protein clusters.
High-res image (130KB JPG)
Murphy home page
Computer-Aided Protein Design Wins Prestigious Science Prize
What started as a sketch of a protein structure has led to a major honor. University of Washington biochemist David Baker and his colleagues recently received the Newcomb Cleveland Prize from the American Association for the Advancement of Science for their work showing that it's possible to design and build a protein with a specific shape. With this ability to create a protein made to order, Baker's research offers a promising new route for developing custom proteins that could be used as drugs or molecular machines to interrupt or enhance a particular reaction inside a cell.
Baker lab home page