Cool Videos: Battling Bad Biofilms

Metabolomics of Bacterial BiofilmsPeriodically, I’ve posted some of the winners of the video competition to celebrate the Tenth Anniversary of the NIH Common Fund. After an intermission of several months, our scientific film fest is back to take another bow. This cool animation shows what some NIH-funded researchers are doing to address a serious health threat: hospital-acquired infections. Such infections can lead to hard-to-heal wounds, such as the foot sores that can trouble people with diabetes, and pressure ulcers in the elderly.

The stubbornness of such wounds owes, in part, to the infection-causing bacteria joining forces to improve their chances of survival within the injury. These microbes literally stick together to form microbial communities, called biofilms, that can resist antibiotics and evade our immune defenses. This strength in numbers has researchers pondering strategies that target the entire biofilm in innovative ways. One promising possibility involves exploiting metabolomics, which tracks the products produced by the bacterial troublemakers, and may provide new perspectives on how to battle this increasingly common healthcare problem.

The video was made by the laboratory of Mary Cloud Ammons at Montana State University in Bozeman. Ammons, who receives research support through the NIH Common Fund to study bacterial metabolomics, describes her work in this way: “The sixth leading cause of death in the United States is the result of hospital-acquired infections, which often result in nonhealing wounds colonized by communities of bacteria call biofilms. The research in our lab aims to uncover the mechanisms at the root of the deviation from the normal healing process that results in the development of chronic wounds. These metabolomic studies identify specific metabolite profiles that may be associated with pathogenicity in the chronic wound and could potentially be used in novel noninvasive diagnostics.”

Links:

Ammons Lab (Montana State University, Bozeman)

Ammons NIH Project Information (NIH RePORTER)

Common Fund (NIH)

Vaccine Research: New Tactics for Tackling HIV

HIV-infected Immune Cell

Caption: Scanning electron micrograph of an HIV-infected immune cell.
Credit: National Institute of Allergy and Infectious Diseases, NIH

For many of the viruses that make people sick—think measles, smallpox, or polio—vaccines that deliver weakened or killed virus encourage the immune system to produce antibodies that afford near complete protection in the event of an exposure. But that simple and straightforward approach doesn’t work in the case of human immunodeficiency virus (HIV), the virus that causes AIDS. In part, that’s because our immune system is poorly equipped to recognize HIV and mount an attack against the infection. To make matters worse, HIV has a habit of quickly mutating as it multiplies.That means, in order for an HIV vaccine to be effective, it must induce antibodies capable of fighting against a wide range of HIV strains. For all these reasons, the three decades of effort to develop an HIV vaccine have turned out to be enormously challenging and frustrating.

But now I’m pleased to report that NIH-funded scientists have taken some encouraging strides down this path. In two papers published in Science [1, 2] and one in Cell [3], researchers presented results of animal studies that support what most vaccine experts have come to suspect: the immune system is in fact capable of producing the kind of antibodies that should be protective against HIV, but it takes more than one step to get there. In effect, a successful vaccine strategy has to “take the immune system to school,” and it requires more than one lesson to pass the final exam. Specifically, what’s needed seems to be a series of shots—each consisting of a different engineered protein designed to push the immune system, step by step, toward the production of protective antibodies that will work against virtually all HIV strains.

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LabTV: Curious about Post-Traumatic Osteoarthritis

LabTV-Avery White

If you like sports and you like science, I think you’ll enjoy meeting Avery White, an undergraduate studying biomedical engineering at the University of Delaware in Newark. In this LabTV profile, we catch up with White as she conducts basic research that may help us better understand—and possibly prevent—the painful osteoarthritis that often pops up years after knee injuries from sports and other activities.

Many athletes, along with lots of regular folks, are familiar with the immediate and painful consequences of tearing the knee’s cartilage (meniscus) or anterior cruciate ligament (ACL). Most also know that such injuries can usually be repaired by surgery. Yet, many people aren’t aware of the longer-term health threat posed by ACL and meniscus tears: a substantially increased risk of developing osteoarthritis years down the road—in some individuals, even as early as age 30. While treatments are available for such post-traumatic osteoarthritis, including physical therapy, pain medications, and even knee-replacement surgery, more preventive options are needed to avoid these chronic joint problems.

White’s interest in this problem is personal. She’s a volleyball player herself, her sister tore her ACL, and her mother damaged her meniscus. After spending a summer working in a lab, this Wilmington, DE native has grown increasingly interested in the field of tissue engineering. She says it offers her an opportunity to use “micro” cell biology techniques to address a “macro” challenge: finding ways to encourage the body to generate healthy new cells that may prevent or reverse injury-induced osteoarthritis.

What’s up next for White? She says maybe a summer internship in a lab overseas, and, on the more distant horizon, graduate school with the goal of earning a Ph.D.

Links:

LabTV

University of Delaware Biomedical Engineering

Science Careers (National Institute of General Medical Sciences/NIH)

Careers Blog (Office of Intramural Training/NIH)

Scientific Careers at NIH

Precision Oncology: Creating a Genomic Guide for Melanoma Therapy

Melanoma cell

Caption: Human malignant melanoma cell viewed through a fluorescent, laser-scanning confocal microscope. Invasive structures involved in metastasis appear as greenish-yellow dots, while actin (green) and vinculin (red) are components of the cell’s cytoskeleton.
Credit: Vira V. Artym, National Institute of Dental and Craniofacial Research, NIH

It’s still the case in most medical care systems that cancers are classified mainly by the type of tissue or part of the body in which they arose—lung, brain, breast, colon, pancreas, and so on. But a radical change is underway. Thanks to advances in scientific knowledge and DNA sequencing technology, researchers are identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that arise in totally different parts of the body can sometimes have a lot in common. Not only can molecular analysis refine diagnosis and provide new insights into what’s driving the growth of a specific tumor, it may also point to the treatment strategy with the greatest chance of helping a particular patient.

The latest cancer to undergo such rigorous, comprehensive molecular analysis is malignant melanoma. While melanoma can rarely arise in the eye and a few other parts of the body, this report focused on the more familiar “cutaneous melanoma,” a deadly and increasingly common form of skin cancer [1].  Reporting in the journal Cell [2], The Cancer Genome Atlas (TCGA) Network says it has identified four distinct molecular subtypes of melanoma. In addition, the NIH-funded network identified an immune signature that spans all four subtypes. Together, these achievements establish a much-needed framework that may guide decisions about which targeted drug, immunotherapy, or combination of therapies to try in an individual with melanoma.

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Snapshots of Life: The Biological Basis of Hearing

sensory hair cells in a chicken's ear

Credit: Peter Barr-Gillespie and Kateri Spinelli, Oregon Health & Science University, Portland

Did you know that chickens have ears? Well, here’s the evidence—you’re looking at a micrograph of sensory hair cells that make up the inner ear of Gallus gallus domesticus, otherwise known as the domestic chicken. Protruding from each hair cell is a tall bundle of stiff appendages, called stereocilia, that capture vibrations and enable the chicken to hear everything from grain being poured into a feeder to the footsteps of a wily fox. The flatter area is occupied by supporting cells, which have recently been shown to have the capacity to regenerate damaged or destroyed hair cells.

Peter Barr-Gillespie and Kateri Spinelli of Oregon Health & Science University, Portland used a scanning electron microscope to capture this image—one of the winners of the Federation of American Societies for Experimental Biology’s 2014 BioArt competition—while studying how these cells convert sound waves into brain waves. It is generally known that sound waves cause the stereocilia on each hair cell to oscillate in concert. These vibrating stereocilia trigger electrical changes in the hair cells, which then send signals to the brain. Barr-Gillespie’s group focuses on the actual molecules that build the stereocilia and translate the vibrations into brain signals.

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