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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... December 15, 2011

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Bacteria under stress

Cool Video: Bet-Hedging Bacteria

Michael Elowitz • California Institute of Technology

This time of year, to many people, blinking lights and stress mean holidays. But to scientists at Caltech, they reveal a new understanding of how bacteria respond-at the genetic level-to a certain type of stress. To track this response, scientists studied the sigma B protein in bacterial cells. When triggered by extreme temperature, starvation or other stressors, sigma B can activate more than 150 genes. The researchers inserted a fluorescent sensor into bacterial cells so that the cells would glow green when sigma B sprang into action. Then they doused the bacteria with a chemical stressor that essentially saps the cells' energy. As expected, sigma B flipped on. But then, just as quickly, it flipped off, even though the chemical remained in the environment. This on-off behavior, which appeared as a blinking green light, reveals that bacteria may "hedge their bets" when exposed to energy stress. This could help bacterial populations survive in changing conditions. Rather than dedicating all their resources for an extended period, the cells offer a brief, dramatic response, then return to their normal state, ready for a different environmental stressor. Because sigma B controls the disease-causing abilities of some bacteria, this research could help us better understand the genetics-and potential weaknesses-of organisms that cause a host of potentially deadly infections.
Fruit fly larval salivary gland. Credit: Lisa Antoszewski and Robert Duronio.

Growing Without Cell Division

Bruce Edgar • Fred Hutchinson Cancer Research Center
George von Dassow • University of Washington
Robert Duronio • University of North Carolina at Chapel Hill

While some cells divide into copies to increase their numbers, others double their genetic material to increase their actual size. To better understand this process called endocycling, researchers studied fruit fly salivary gland cells, which endocycle about 10 times during the fly's lifetime and increase in size by more than 1,000-fold. The scientists identified how specific proteins function as a molecular oscillator to drive the process. Since endocycling occurs in most plants and invertebrate animals, the findings could lead to improved agricultural methods. They also are relevant to human diseases that involve cells that endocycle, such as placental, heart, blood and liver cells. Read more... Link to external Website

Caption: Fruit fly larval salivary gland showing nuclei (blue), DNA replication (red) and replication-coupled gene expression (green). Credit: Lisa Antoszewski and Robert Duronio. High res. image (JPG, 59KB)
 BCL6 (small, bright green spots) in a B-cell nucleus (blue central forcus of image). Credit: Michele Pagano.

New Therapeutic Target for Aggressive Lymphoma

Michele Pagano • NYU Langone Medical Center

Diffuse Large B-cell Lymphoma is the most common type of lymphoma in adults. It has been linked to an overabundance of BCL6—a protein that binds DNA and regulates gene activities, including genes that control B-cell differentiation. Researchers have now uncovered one reason for the excess. A protein called FBXO11 normally helps keep BCL6 levels low by targeting it for degradation. But when the FBXO11 gene is mutated or deleted, BCL6 levels rise and cells can turn malignant. The discovery of FBXO11's role offers a promising new therapeutic target for treating the disease. Read more... Link to external Website

Caption: BCL6 (green) in a B-cell nucleus (blue). Credit: Michele Pagano. High res. image (JPG, 35KB)
Structure of heparin molecule

Faster, Less Expensive Way to Make Heparin

Robert Linhardt • Rensselaer Polytechnic Institute

For more than 70 years, doctors have relied on a class of drugs called heparins to decrease the risk of blood clots in their patients. But heparins, which are made of carbohydrate subunits, are tricky to manufacture. Synthesis of one version of the drug requires 50 steps and generates large quantities of hazardous waste. A new method that uses a combination of chemical and enzymatic processes enables drug production in just 10 or 12 steps. This more efficient approach is expected to significantly reduce the cost of the medicine and may even be adapted to the synthesis of other drugs. Read more... Link to external Website

Caption: Chemical structure of heparin molecule manufactured using new, streamlined method. Credit: Robert Linhardt. High res. image (JPG, 34KB)

Hydrogen Peroxide Channel Sheds Light on Wound Healing, Tumors

Anna Huttenlocher • University of Wisconsin-Madison

In response to a cut or other wound, the human body produces its own hydrogen peroxide to ward off infection and start the healing process. Scientists found that such wound-induced hydrogen peroxide triggers a protein, called Lyn, that routes white blood cells and immune cells down a particular cellular pathway. While this process is ideal for healing infections, it can stimulate tumor growth and cause inflammation. By blocking Lyn, researchers reduced the recruitment of white blood cells to wounds. The finding could provide a better understanding of cancer and wound healing. Read more... Link to external Website

Caption: White blood cells gather at wound sites and start the healing process. Credit: Jonathan Moore.

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This page last reviewed on December 15, 2011