In This Issue... September 20, 2012

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Cool Video: Repurposing Genes, Repurposing Drugs

Edward Marcotte • University of Texas at Austin

Although they are single-celled fungi, yeast like this Saccharomyces cerevisiae specimen have genes in common with other, more complex organisms, including humans, by virtue of their shared evolutionary history. For example, yeast have a gene, rab11b, that becomes active when they experience environmental stressors like heat. That gene in yeast, which have no blood, has been repurposed to regulate vein and artery growth in vertebrates like frogs, mice and humans. Scientists studied that gene to find a drug that could keep new blood vessels from forming. Stopping this formation could aid cancer treatments because tumors recruit new blood vessels to feed their growth. In searching for a molecule that would block the yeast gene, the researchers found an unlikely candidate—thiabendazole, an anti-parasitic agent with anti-fungal activity. Following up with more studies, the researchers showed that the compound reduced the growth of blood vessels in frog embryos and inhibited the growth of human blood vessel cells. Thiabendazole also decreased the emergence of new blood vessels and reduced the size of tumors in mice with cancer. In addition to their potential cancer treatment applications, the findings more generally demonstrate the value of an evolutionary approach to drug development. Read more...

Three Human Antibodies Provide Broad Protection Against Flu

Ian Wilson • The Scripps Research Institute

Wishing that a flu shot could provide long-term protection against influenza? New findings by an international research team might help make that possible. The scientists screened immune cells of people who had received a seasonal flu shot to find their antibodies against influenza B strains, which account for much of the annual flu illness burden in humans. Three antibodies that they identified protected mice against normally lethal doses of two influenza B strains, and one of those also protected against the more virulent A strains. Structural studies later revealed how the antibodies bind to and neutralize the virus. These advances could provide clues to the design of a universal flu vaccine. Read more...

Caption: Three antibodies (represented in blue, green and yellow) provide broad protection against influenza B virus strains. Credit: Wilson Lab, The Scripps Research Institute. High res. image (JPG, 166KB)

Bacterial Gene Teams Cut Down on Signal Noise

Oleg Igoshin • Rice University

While human genes are controlled individually, bacterial genes are often turned on and off in sets through a single control point. A computational study has revealed a possible explanation for the difference. Because of their small size, bacteria are particularly susceptible to “noise” in the signals that activate genes. This noise can cause ill-timed and potentially detrimental gene activation. Computer models showed that regulating bacterial genes in sets can quiet the noise, lessening potentially harmful fluctuations. This discovery may prove useful for scientists striving to genetically engineer bacteria with new biological functions, such as production of a drug. Read more...

Caption: Genes on bacterial chromosomes are organized into operons—clusters with a single point of control. Credit: Oleg Igoshin, Rice University. High res. image (JPG, 71KB)

Cancer Uses Special Sugar to Usurp Cells

Linda Hsieh-Wilson • California Institute of Technology

Scientists found another way cancerous cells boost their growth and overtake normal cells: They add a “sugar tag” to an enzyme abbreviated PFK1. This tag cripples PFK1, shifting the cell away from producing energy and forcing it to make materials that promote the cell’s survival and rapid growth—hallmarks of cancer. The researchers believe that finding ways to prevent the tag from attaching to PFK1 could open doors to new cancer treatments. Read more...

Caption: The PFK1 enzyme (left) helps cells make energy. In cancer cells, a specific sugar attaches to PFK1 (right), inactivating the enzyme and redirecting the cells to make molecules that promote their survival and aggressive growth. Credit: Linda Hsieh-Wilson, California Institute of Technology. High res. image (JPG, 110KB)

Computerized Sorter Helps Detect Subtle Difference in Worms

Hang Lu • Georgia Institute of Technology

Humans are good at recognizing patterns, but computers are even better! Using artificial intelligence and image processing techniques, researchers developed a new system that can rapidly examine thousands of microscopic roundworms—a model organism used to understand human biology. As the worm passes through the microfluidic sorter, a camera captures its image and compares it to normal worms. Worms with slight abnormalities are identified and removed for further study. By providing a valuable tool for high-throughput screening, the new technology could lead to a deeper understanding of developmental processes and the genetics of certain diseases. Read more...

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

Caption: A microfluidic chip helps to automatically examine a large number of roundworms used for genetic research. Credit: Gary Meek. High res. image (JPG, 35KB)