In This Issue... May 16, 2013

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Cool Image: Chewing up Proteins

Hermann Steller • Rockefeller University

All cells, such as the fruit fly spermatid shown here, recycle various molecules, including malformed or damaged proteins. How? Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use. New research reveals the role of one enzyme, tankyrase, in the regulation of such protein degradation. In a preliminary study, a molecule originally developed to treat colon cancer inhibits tankyrase, thus blocking proteasome activity. Because abnormally high rates of proteasome activity have been linked to cancer, the findings may be clinically useful. Read more…

A Universe of Unexplored Small Molecules

Peter Wipf • University of Pittsburgh

The observable universe contains fewer stars than the number of unique organic compounds that could be developed for medical purposes. With such a huge number of molecules, it’s often difficult for chemists to identify and then make the ones with the most therapeutic benefit for a given ailment. Researchers have developed a computer algorithm that may help. It plots all known small carbon-based molecules as though they were cities on a map and identifies huge, unexplored spaces that may help fuel research into new drug therapies. Read more...

Caption: Plot of known organic molecules generated by the algorithm. Credit: Aaron Virshup, Julia Contreras-García, Peter Wipf, Weitao Yang and David Beratan, University of Pittsburgh Center for Chemical Methodologies and Library Development; Journal of the American Chemical Society. High res. image (JPG, 126KB)

Gene Blocks Appetite Suppression

Xiaodong Cheng • University of Texas Medical Branch at Galveston

When scientists discovered in 1994 that the hormone leptin suppresses appetite, they saw it as a promising way to control obesity and diabetes. Now scientists have shed light on one potential mechanism of leptin regulation. They found that mice that lacked a gene called Epac1 had higher sensitivity to leptin. When placed on a high-fat diet, the mice weighed less, were leaner and had lower blood-plasma levels than their counterparts with the gene. A specially developed compound that blocked Epac1 activity in the mice with the gene also significantly reduced leptin levels, another indication that Epac1 contributes to leptin’s action. This work demonstrates the feasibility of pharmacologically modulating leptin through Epac1 activity. Read more...

This work also was supported by NIH’s National Heart, Lung, and Blood Institute and National Institute on Drug Abuse.

Caption: Scientists determined the effect of the Epac1 gene on leptin regulation in mice and in human cells.

Structure of Critical Enzyme Linked to Cancer and Aging

Juli Feigon and Z. Hong Zhou • University of California, Los Angeles
Kathleen Collins • University of California, Berkeley

Using a combination of techniques, researchers have determined the complete molecular structure of telomerase, the enzyme that preserves genetic information by maintaining chromosome endings called telomeres. First discovered in Nobel Prize-winning work on the microorganism Tetrahymena thermophila, telomeres shorten with every cell division as part of the normal aging process. When they become too short, the cell dies. Telomerase counteracts this by preventing the telomeres from becoming too short. However, abnormally high levels of telomerase activity may extend the lifespan of a cell beyond the normal limit, leading to cancer. The new structural details of telomerase may aid efforts to develop drugs that target the enzyme and shorten cancer cells’ lifespans. Read more...

This work also was supported by NIH’s National Institute of Allergy and Infectious Diseases.

Caption: The structure of telomerase. Credit: Jiansen Jiang, Edward J. Miracco, Z. Hong Zhou and Juli Feigon, University of California, Los Angeles; Kathleen Collins, University of California, Berkeley. High res. image (JPG, 112KB)

Stickiness Helps Sort Stem Cells

Andrés García • Georgia Institute of Technology

Information about how strongly different cells stick to surfaces has allowed researchers to develop a faster, more efficient way of isolating human induced pluripotent stem (iPS) cells. The method uses a microfluidic device to which cells, including human iPS cells, adhere well. When a cell culture attached to the device is exposed to the flow of a fluid, the iPS cells hang on while others are swept away. The technique results in a greater than 95 percent pure human iPS cell culture. The researchers predict that the method could be scaled up, thereby speeding progress toward potential stem cell-based therapies.
Read more...

This work also was supported by NIH’s National Institute of Neurological Disorders and Stroke and National Cancer Institute.

Caption: Actin stress fibers (magenta) and the protein vinculin (green) help make adhesion possible. Credit: Ankur Singh and Andrés García, Georgia Institute of Technology. High res. image (JPG, 238KB)