Creative Minds: Of Arsenic and Misfolded Proteins

John Hanna

John Hanna

Taking out the trash is a must in every household. Inside our cells, it’s also essential because if defective proteins are not properly disposed of, they can accumulate and make a mess of the cell’s inner workings, leading to health problems.

John Hanna, a physician-scientist at Brigham and Women’s Hospital, Boston, is on a quest to study the cell’s trash disposal system in greater detail. In particular, this 2014 NIH Director’s Early Independence awardee wants to learn more about how cells identify proteins that need to be discarded, how such proteins are steered towards the molecular garbage can, and how, when the process breaks down, neurodegenerative conditions, cancers, and other diseases can arise.

That’s a complex challenge, so Hanna will start by zeroing in on one particular component of cellular waste management—the component that clears out proteins damaged by arsenic. Although arsenic is notorious for being the poison of choice in countless true crime shows and mystery novels, this semi-metallic element is found naturally in soil, water, air, and some foods.

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Creative Minds: Searching for Solutions to Chronic Infection

Kyle R. Allison

Kyle R. Allison

If you or a loved one has ever struggled with a bacterial infection that seemed to have gone away with antibiotic treatment, but then came back again, you’ll probably be interested to learn about the work of Kyle Allison. What sometimes happens when a person has an infection—for instance, a staph infection of the skin—is that antibiotics kill off the vast majority of bacteria, but a small fraction remain alive. After antibiotic treatment ends, those lurking bacterial “persisters” begin to multiply, and the person develops a chronic infection that may be very difficult and costly to eliminate.

Unlike antibiotic-resistant superbugs, bacterial persisters don’t possess any specific genetic mutations that protect them against the killing power of one particular medication or another. Rather, the survival of these bacteria depends upon their ability to enter a dormant state that allows them to hang on in the face of antibiotic treatment. It isn’t clear exactly how the bugs do it, and that’s where Kyle’s work comes in.

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LabTV: Curious about the Aging Brain

Saul Villeda

This LabTV video takes us to the West Coast to meet Saul Villeda, a creative young researcher who’s exploring ways to reduce the effects of aging on the human brain. Thanks to a 2012 NIH Director’s Early Independence award, Villeda set up his own lab at the University of California, San Francisco to study how age-related immune changes may affect the ability of brain cells to regenerate. By figuring out exactly what’s going on, Villeda and his team hope to devise ways to counteract such changes, possibly preventing or even reversing the cognitive declines that all too often come with age.

Villeda is the first person in his family to become a scientist. His parents immigrated to the United States from Guatemala, settled into a working-class neighborhood in Pasadena, CA, and enrolled their kids in public schools. While he was growing up, Villeda says he’d never even heard of a Ph.D. and thought all doctors were M.D.’s who wore stethoscopes. But he did have a keen mind and a strong sense of curiosity—gifts that helped him become the valedictorian of his high school class and find his calling in science. Villeda went on to earn an undergraduate degree in physiological science from the University of California, Los Angeles and a Ph.D. in neurosciences from Stanford University Medical School, Palo Alto, CA, as well as to publish his research findings in several influential scientific journals.

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Creative Minds: Michael Angelo’s Art

Multiplexed image of breast cancer cells

Caption: The location and abundance of six proteins—e-cadherin (green), vimentin (blue), actin (red), estrogen receptor, progesterone receptor, and Ki67—found in breast cancer cells are seen in this multiplexed ion beam image. Cells positive for estrogen receptor a, progesterone receptor, and Ki-67 appear yellow; cells expressing estrogen receptor a and the progesterone receptor appear aqua.
Credit: Michael Angelo

The artistic masterpiece above, reminiscent of a stained glass window, is the work of Michael Angelo—no, not the famous 16th Century Italian artist, but a 21st Century physician-scientist who’s out to develop a better way of looking at what’s going on inside solid tumors. Called multiplexed ion beam imaging (MIBI), Angelo’s experimental method may someday give clinicians the power to analyze up to 100 different proteins in a single tumor sample.

In this image, Angelo used MIBI to analyze a human breast tumor sample for nine proteins simultaneously—each protein stained with an antibody tagged with a metal reporter. Six of the nine proteins are illustrated here. The subpopulation of cells that are positive for three proteins often used to guide breast cancer treatment (estrogen receptor a, progesterone receptor, Ki-67) have yellow nuclei, while aqua marks the nuclei of another group of cells that’s positive for only two of the proteins (estrogen receptor a, progesterone receptor). In the membrane and cytoplasmic regions of the cell, red indicates actin, blue indicates vimentin, which is a protein associated with highly aggressive tumors, and the green is E-cadherin, which is expressed at lower levels in rapidly growing tumors than in less aggressive ones. Taken together, such “multi-dimensional” information on the types and amounts of proteins in a patient’s tumor sample may give oncologists a clearer idea of how quickly that tumor is growing and which types of treatments may work best for that particular patient.  It also shows dramatically how much heterogeneity is present in a group of breast cancer cells that would have appeared identical by less sophisticated methods.

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Creative Minds: A Baby’s Eye View of Language Development

Click to start videoIf you are a fan of wildlife shows, you’ve probably seen those tiny video cameras rigged to animals in the wild that provide a sneak peek into their secret domains. But not all research cams are mounted on creatures with fur, feathers, or fins. One of NIH’s 2014 Early Independence Award winners has developed a baby-friendly, head-mounted camera system (shown above) that captures the world from an infant’s perspective and explores one of our most human, but still imperfectly understood, traits: language.

Elika Bergelson

Elika Bergelson
Credit: Zachary T. Kern

Elika Bergelson, a young researcher at the University of Rochester in New York, wants to know exactly how and when infants acquire the ability to understand spoken words. Using innovative camera gear and other investigative tools, she hopes to refine current thinking about the natural timeline for language acquisition. Bergelson also hopes her work will pay off in a firmer theoretical foundation to help clinicians assess children with poor verbal skills or with neurodevelopmental conditions that impair information processing, such as autism spectrum disorders.

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