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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.

In This Issue... July 19, 2012

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Screenshot from the Meticulous Molecular Modeling video

Cool Video: Meticulous Molecular Modeling

Chandrajit Bajaj • University of Texas at Austin

Though it may look like a psychologist's inkblot test, this image depicts part of a ribosome, a biological machine that makes proteins. Each dot represents an individual atom. Scientists have developed software to visualize this and other large molecular machines, giving way to three-dimensional moving models. To create this 3-D image of the ribosome, researchers used their software to process data from electron microscopes, which shoot electrons through samples. Then they fed the output—thousands of speckled pictures at the nanoscale level—plus all the other chemical, biological and structural information they had, into data-modeling software. After the computers combined everything, the scientists had reconstructed a 3-D model. In this video simulation, a ribosome adds amino acids to a peptide chain. The end result is a protein. Proteins are involved in virtually every cellular process, making their structures relevant to how medicines work. Such three-dimensional modeling allows researchers to better understand not only proteins' shapes, but how they're made and how they interact with other molecules. Together, this knowledge could possibly point the way to more efficient drug development. Read more... Link to external Website

This work also was supported by NIH's National Institute of Biomedical Imaging and Bioengineering.

Prions (red) and huntingtin protein (green) within cells' aggresomes. Credit: Yury Chernoff.

Toxicity of Huntington's Disease Protein Linked to Other Proteins

Yury Chernoff • Georgia Institute of Technology
Michael Sherman • Boston University School of Medicine

The neurodegenerative Huntington's disease is associated with a mutation that causes an expansion of the huntingtin protein. A new study suggests that having certain other proteins can alter huntingtin's toxic effects. Cells package huntingtin proteins in protective compartments called aggresomes, but researchers working with yeast found that even in the aggresome the elongated huntingtin protein can still be harmful. In the same study, they observed that the protein's toxicity could be increased in the presence of some (but not other) prions, a special type of protein that can take on different shapes. Many questions remain, but this early work suggests a potential new therapeutic target for treating Huntington's disease. Read more... Link to external Website

Caption: A group of prions (red) clumps together with elongated versions of the huntingtin protein (green) within cells' aggresomes. Credit: Yury Chernoff. High res. image (JPG, 23KB)
Protein tail (red) of the p65 protein. Credit: Mahavir Singh and Juli Feigon.

Researchers Uncover How "Immortality" Enzyme is Constructed

Juli Feigon • University of California, Los Angeles
Kathleen Collins • University of California, Berkeley

The enzyme telomerase adds segments to the end of DNA strands, dictating how many times the cell can divide before dying. This telomerase activity is important in both aging and most cancers. In an effort to better understand how the enzyme forms, researchers have now determined the structure of a key component of a protein bound to telomerase RNA from the model organism Tetrahymena thermophila. The protein, called p65, has a flexible tail that inserts into the RNA helix and bends it into a scaffold. This aids the assembly of the enzyme's catalytic core, where the chemistry happens. The finding could help scientists also understand how related proteins interact with diverse RNAs in human cells. Read more... Link to external Website

Caption: The protein tail (red) of the p65 protein (left) pries apart the telomerase RNA double helix (right), causing it to change shape and making way for the next step in telomerase's assembly. Credit: Mahavir Singh and Juli Feigon. High res. image (JPG, 286KB)
Inhibitor (dark blue) and human multidrug resistance protein (purple, turquoise and yellow). Credit: John Wise.

3-D Protein Model Could Improve Cancer Therapies

Pia Vogel and John Wise • Southern Methodist University

Scientists estimate that up to 40 percent of all human cancers develop multidrug resistance, making many chemotherapy treatments ineffective. At the heart of this phenomenon may be the aptly named multidrug resistance protein. The protein pumps toxins from cells, and cancer cells with lots of the protein use it to flush chemotherapy drugs out. Researchers now have developed a three-dimensional moving model of the multidrug resistance protein, and they're using it to find possible drugs that block the protein. With the help of supercomputers, the researchers have screened about 8 million compounds and found some that could plug the pump. Their work could lead to medicines that make chemotherapy more effective. Read more... Link to external Website

Caption: A new inhibitor (dark blue) could keep the human multidrug resistance protein (purple, turquoise and yellow) from rejecting chemotherapy. Credit: John Wise. High res. image (JPG, 105KB)
DNA that makes up genes is spooled within chromosomes inside the nucleus of a cell. Credit: NIGMS

Genetics by the Numbers

How many human genes are there? How long is our DNA? How much of your DNA is the same as the person sitting next to you? Since scholars began studying modern genetics in the mid-19th century, they've made some astounding discoveries about genes and inheritance—and every day they're learning more. Get some stats in "Genetics by the Numbers," part of NIGMS' Inside Life Science series. Read more...

Caption: The length of DNA, the number of human chromosome and the size of the nucleus are some of the stats given in "Genetics by the Numbers." Credit: NIGMS. High res. image (JPG, 175KB)

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This page last reviewed on June 21, 2011