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NIH Director Blogs About NIGMS-Funded Research

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Antifolate drugs (bottom) work by blocking the folate receptor (top). Credit: Charles Dann III, Indiana University.
Caption: Antifolate drugs (bottom) work by blocking the folate receptor (top), starving cancer cells of an essential vitamin. Credit: Charles Dann III, Indiana University.

Within the last few weeks, NIH Director Francis Collins has blogged about several findings that NIGMS helped fund: the identification of a genetic link between hair color and melanoma risk and the solving of human folate receptor structures, which may aid the design of drugs for cancer and inflammatory diseases like rheumatoid arthritis and Crohn’s disease. Both advances are excellent examples of the value and impact of basic research. Want more examples? Check out Curiosity Creates Cures!

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Cool Image: Tiny Bacterial Motor

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Phillip Klebba, Kansas State University.

Credit: Phillip Klebba, Kansas State University.

It looks like a fluorescent pill, but this image of an E. coli cell actually shows a new potential target in the fight against infectious diseases. The green highlights a protein called TonB, which is produced by many gram-negative bacteria, including those that cause typhoid fever, meningitis and dysentery. TonB lets bacteria take up iron from the host’s body, which they need to survive. New research from Phillip Klebba of Kansas State University and his colleagues shows how TonB powers iron uptake. When TonB spins within the cell envelope (the bacteria’s “skin”) like a tiny motor, it produces energy that lets another protein pull iron into the cell. This knowledge may lead to the development of antibiotics that block the motion of TonB, potentially stopping an infection in its tracks.

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Gut Microbes Can Inactivate Cardiac Drugs

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Digoxin bacteria. Credit: CDC.

Bacteria in the gut can inactivate some of the medicines we take. Credit: CDC.

Doctors have known that a medication often prescribed to treat heart failure is inactivated by gut microbes, particularly a bacterial species called E. lenta. Now scientists have a better understanding of why. A Harvard University research team led by Peter Turnbaugh found that the heart drug digoxin turns on two E. lenta genes that help convert the drug into its inactive form, thereby making the medicine less effective. By measuring gene abundance, the scientists could reliably predict whether a microbial community could break down the drug. The researchers also identified a possible way to stop the process: add protein. Their studies using mice showed that a diet high in protein—and the amino acid, arginine, that helps E. lenta grow—increased digoxin absorption. These initial findings suggest that one day it may be possible to tailor digoxin therapy through diet modifications.

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Silencing Extra Copy of Chromosome 21

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Each year about 1 in 700 babies is born with Down syndrome, a condition that occurs when cells contain three copies of chromosome 21. A new technique offers a proof of principle for silencing the extra copy. Using induced pluripotent stem cells derived from a person with Down syndrome, a research team led by Jeanne Lawrence of the University of Massachusetts Medical School inserted a gene called XIST into the extra chromosome 21. The gene, which normally turns off one whole X chromosome in females, rendered the chromosome copy and most of its genes inactive. The researchers plan to test the approach in a mouse model of Down syndrome and use it to further explore the biology of chromosome errors. The findings could eventually aid the development of therapies to mitigate resulting medical problems.

This work also was funded by NIH’s National Cancer Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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New Door Opens in the Effort to Stave off Mosquito-Borne Diseases

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Mosquito net Pyrethroids are used in mosquito nets distributed around the globe. Credit: Kurt Stepnitz, Michigan State University.

In the past decade, mosquitoes in many countries have become increasingly resistant to pyrethroid insecticides used to fend off mosquito-borne diseases such as malaria and dengue fever. Now, Ke Dong of Michigan State University and her colleagues have discovered a second pyrethroid-docking site in the molecular doorways, or channels, that control the flow of sodium into cells. Pyrethroids paralyze and kill mosquitoes and other insects by propping open the door and causing the pests to overdose on sodium, a critical regulator of nerve function. By providing new insights on pyrethroid action at the molecular level—and how mutations in the dual docking sites cause resistance—the findings open avenues to better monitoring and management of insecticide resistance.

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Genes Linked to Aspirin Effectiveness

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Pill bottle

Aspirin is a blood thinner used to prevent heart attacks and stroke.

Aspirin is used often to prevent heart attacks and stroke. Yet, doctors know little about why it’s more effective in some people than others. A team of Duke University researchers, including Geoffrey Ginsburg and Deepak Voora, recently discovered a method to pinpoint the patients who benefit most from the drug as well as those who are at risk for heart attacks. By administering aspirin to a set of healthy volunteers and people with heart disease and then analyzing their gene activity patterns, the researchers identified a set of genes that correlate with insufficient platelet response to aspirin. The finding might lead to a simple blood test to help tailor treatments for heart disease.

NIH’s National Heart, Lung, and Blood Institute also supported this work.

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Meet David Patterson

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David Patterson
David Patterson
Field: Psychology
Works at: University of Washington, Seattle
Alternative career: Full-time rock ‘n’ roll drummer
Hobbies: Part-time rock ‘n’ roll drummer (with his band, the Shrinking Heads)
Credit: Clare McLean, UW Medicine Strategic Marketing & Communications

The pain stemming from second- and third-degree burns is among the worst known. Throughout recovery, the intense, disabling pain patients feel can lead to sleeplessness, anxiety and depression.

David Patterson first entered a burn ward as a psychologist hoping to help patients cope with these issues. He saw patients refuse wound cleaning because of how painful it could be.

“I’ve learned how horribly difficult it is to control burn and trauma pain with medications alone,” he says. “The amount of pain people feel affects how well they adjust in the long term.” Pain and the mental, social and emotional problems it causes also hinder the body’s ability to heal physically.

Today, Patterson is committed to helping burn patients overcome pain, allowing their bodies—as well as their minds—to heal more efficiently. Using virtual reality (VR) technology, Patterson has found an effective complement to pain-relieving drugs such as morphine and other opioid analgesics.

Patterson’s Findings

“To be honest, for acute pain, you give someone a shot or a pill and it’s instant relief,” Patterson says. But opioid analgesics carry problems.  Sometimes patients don’t respond well to morphine or require high dosages that carry strong side effects.

When burn patients undergo routine wound care, the pain can be excruciating—as bad as or worse than the original burn incident. Realizing the brain can take only so many stimuli, Patterson collaborated with fellow UW psychologist Hunter Hoffman to experiment with VR in pain relief. When combined with minimal pain medications, VR is a powerful solution to acute pain. By providing a computer-generated reality—for example, an icy canyon filled with snowmen and Paul Simon’s music, as in the case of their creation SnowWorld—the patient’s eyes, ears and mind are so occupied that he or she can effectively ignore the pain.

Patterson and his team found that VR pain reduction strategies are as powerful as opioid analgesics, without the negative side effects. The technology doesn’t require specialized expertise and is getting progressively less expensive, making it economically attractive.  At least eight hospitals have adopted the methods as part of their clinical program, allowing Patterson an opportunity to conduct further studies on the long-term effects of using these complementary methods and the efficacy of the techniques on other kinds of pain.

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