Snapshots of Life: Lost Connections in Pompe Disease

Junctions between motor neurons (green) and muscle fibers (red)

Caption: Abnormal connections between leg muscle fibers (red) and nerves (green) in Pompe disease.
Credit: Darin J. Falk, A. Gary Todd, Robin Yoon, and Barry J. Byrne, University of Florida, Gainesville

Mistletoe? Holly? Not exactly. This seemingly festive image is a micrograph of nerve cells (green) and nerve-muscle junctions (red) in a mouse model of Pompe disease. Such images are helping researchers learn more about this rare form of muscular dystrophy, providing valuable clues in the ongoing search for better treatments and cures.

People with Pompe disease lack an enzyme that cells depend on to break down a stored sugar, known as glycogen, into smaller glucose molecules that can be readily used for energy. Without enough of this enzyme, called acid alpha-glucosidase (GAA), glycogen can accumulate destructively in the liver, heart, and skeletal muscles, making it increasingly difficult to walk, eat, and even breathe.

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Genome Sequencing: Exploring the Diagnostic Promise

Hanners Family

Caption: Whole genome sequencing revealed that sisters Addison and Trinity Hanners, ages 7 and 10, shown here with their mother Hanna, have a rare syndrome caused by a mutation in the MAGEL2 gene.
Credit: Courtesy of the Hanners family

At the time that we completed a draft of the 3 billion letters of the human genome about a decade ago, it would have cost about $100 million to sequence a second human genome. Today, thanks to advances in DNA sequencing technology, it will soon be possible to sequence your genome or mine for  $1,000 or less. All of this progress has made genome sequencing a far more realistic clinical option to consider for people, especially children, who suffer from baffling disorders that can’t be precisely diagnosed by other medical tests.

While researchers are still in the process of evaluating genome sequencing for routine clinical use, and data analysis continues to be a major challenge, one area of considerable promise centers on neurodevelopmental disorders. Such disorders—which affect about 3 percent of children—range from relatively common conditions like autism spectrum disorder to very rare conditions that impair the development of the brain or central nervous system. In the latest study, an NIH-funded research team reports that sequencing either a patient’s whole genome or whole exome (the 1.5 percent of the genome that encodes proteins) appears to be an effective—as well as a cost-effective—strategy for diagnosing neurodevelopmental disorders that have eluded diagnosis through standard means.

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Cool Videos: Know When to Fold Them

Hi-C Video Screenshot

As most of you probably know, the human genome—our genetic instruction book—contains about 3 billion base pairs of DNA. But here’s a less well-known fact: if you would take the DNA from the nucleus of just one human cell and stretch it end-to-end, it would measure about 6 1/2 feet. How can a molecule of that length be packed into a cell nucleus that measures less than .00024 of an inch? Well, this fun video, which accompanies exciting new findings published in the journal Cell, serves to answer that fundamental question.

I’m proud to say that NIH helped to support the highly creative team of researchers that, over the course of the past five years, have mapped with unprecedented detail and precision how the human genome folds inside the cell’s nucleus. Among the many things they’ve learned is that, in much the same way that origami artists can craft a vast array of paper creatures using two simple folds, the genome is able to work its biological magic with just a few basic folds—including the all-important 3D loop

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Alzheimer’s-in-a-Dish: New Tool for Drug Discovery

Alzheimer's Disease in a dish

Caption: A plaque (orange) disrupts the normal network of human neurons (green) grown in a three-dimensional gel in the lab, mimicking the brain anatomy of Alzheimer’s patients.
Credit: Doo Yeon Kim and Rudolph E. Tanzi, Massachusetts General Hospital/ Harvard Medical School

Researchers want desperately to develop treatments to help the more than 5 million Americans with Alzheimer’s disease and the millions more at risk. But that’s proven to be extremely challenging for a variety of reasons, including the fact that it’s been extraordinarily difficult to mimic the brain’s complexity in standard laboratory models. So, that’s why I was particularly excited by the recent news that an NIH-supported team, led by Rudolph Tanzi at Boston’s Massachusetts General Hospital, has developed a new model called “Alzheimer’s in a dish.”

So, how did Tanzi’s group succeed where others have run up against a brick wall? The answer appears to lie in their decision to add a third dimension to their disease model.  Previous attempts at growing human brain cells in the lab and inducing them to form the plaques and tangles characteristic of Alzheimer’s disease were performed in a two-dimensional Petri dish system. And, in this flat, 2-D environment, plaques and tangles simply didn’t appear.

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President’s Visit to NIH Highlights Research on Ebola

President during NIH lab visit

Caption: Dr. Nancy Sullivan of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) discussing Ebola research with President Barack Obama as NIAID Director Dr. Anthony Fauci and HHS Secretary Sylvia Burwell look on.
Credit: NIH

Today, we had the great honor of welcoming President Barack Obama to the campus of the National Institutes of Health (NIH) in Bethesda, MD—to see first-hand the progress that biomedical research is making against Ebola virus disease. The President toured the NIH Vaccine Research Center, and met with scientists who are working hard to develop ways to combat this deadly virus that continues to devastate West Africa. And, in a speech before a packed auditorium at the NIH Clinical Center, the President praised the contributions of NIH staff. He also emphasized the need for emergency Congressional authorization of resources to ensure that our nation’s research and public health efforts against Ebola will lead as quickly as possible to an end to this devastating outbreak.

The President heard about many encouraging advances against Ebola during his visit here, and I’d like to share a couple with you now. I think these examples—one about a vaccine and one about a treatment—speak to the extraordinary ways in which scientists from different fields, disciplines, and organizations are pulling together to tackle this urgent disease threat.

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