Creative Minds: A New Mechanism for Epigenetics?

Keith Maggert

Keith Maggert

To learn more about how DNA and inheritance works, Keith Maggert has spent much of his nearly 30 years as a researcher studying what takes place not just within the DNA genome but also the subtle modifications of it. That’s where a stable of enzymes add chemical marks to DNA, turning individual genes on or off without changing their underlying sequence. What’s really intrigued Maggert is these “epigenetic” modifications are maintained through cell division and can even get passed down from parent to child over many generations. Like many researchers, he wants to know how it happens.

Maggert thinks there’s more to the story than scientists have realized. Now an associate professor at the University of Arizona College of Medicine, Tucson, he suspects that a prominent subcellular structure in the nucleus called the nucleolus also exerts powerful epigenetic effects. What’s different about the nucleolus, Maggert proposes, is it doesn’t affect genes one by one, a focal point of current epigenetic research. He thinks under some circumstances its epigenetic effects can activate many previously silenced, or “off” genes at once, sending cells and individuals on a different path toward health or disease.

Maggert has received a 2016 NIH Director’s Transformative Research Award to pursue this potentially new paradigm. If correct, it would transform current thinking in the field and provide an exciting new perspective to track epigenetics and its contributions to a wide range of human diseases, including cancer, cardiovascular disease, and neurodegenerative disorders.

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Out of Africa: DNA Analysis Points to a Single Major Exodus

View of Africa from space

Credit: NASA

If you go back far enough, the ancestors of all people trace to Africa. That much is clear. We are all Africans. But there’s been considerable room for debate about exactly when and how many times modern humans made their way out of Africa to take up residence in distant locations throughout the world. It’s also unclear what evolutionary or other factors might have driven our human ancestors to set off on such a perilous and uncertain journey (or journeys) in the first place.

By analyzing 787 newly sequenced complete human genomes representing more than 280 diverse and understudied populations, three new studies—two of which received NIH funding—now help to fill in some of those missing pages of our evolutionary history. The genomic evidence suggests that the earliest human inhabitants of Eurasia came from Africa and began to diverge genetically at least 50,000 years ago. While the new studies differ somewhat in their conclusions, the findings also lend support to the notion that our modern human ancestors dispersed out of Africa primarily in a single migratory event. If an earlier and ultimately failed voyage occurred, it left little trace in the genomes of people alive today.

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What Makes Our Brain Human? The Search for Answers

The Thinker

“The Thinker” by Auguste Rodin (photo by Brian Hillegas)

Humans’ most unique traits, such as speaking and abstract thinking, are rooted in the outer layer of our brains called the cerebral cortex. This convoluted sheet of grey matter is found in all mammals, but it is much larger and far more complex in Homo sapiens than in any other species. The cortex comprises nearly 80 percent of our brain mass, with some 16 billion neurons packed into more than 50 distinct, meticulously organized regions.

In an effort to explore the evolution of the human cortex, many researchers have looked to changes in the portion of the genome that codes for proteins. But a new paper, published in the journal Science [1], shows that protein-coding DNA provides only part of the answer. The new findings reveal that an even more critical component may be changes in the DNA sequences that regulate the activity of these genes.

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Ferreting Out Genomic Secrets

Ferret

Ferret in a Colorado conservation center, U.S. Fish and Wildlife Service

Not only is the ferret (Mustela putorius furo) adept at navigating a dirt field or threading electrical cables through piping (in New Zealand, ferrets can be registered as electrician assistants), this furry 5-pounder ranks as a real heavyweight for studying respiratory diseases. In fact, much of our current thinking about influenza is influenced by research with ferrets.

Now, the ferret will stand out even more. As reported online in Nature Biotechnology, NIH-funded researchers recently sequenced the genome of the sable ferret, the type that is bred in the United States as a pet. By studying this genetic blueprint like an explorer would a map, scientists can perform experiments to learn more systematically how the ferret copes biologically with common or emerging respiratory pathogens, pointing the way to improved strategies to preserve the health and well being of humans and ferrets alike.

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Using Genomics to Follow the Path of Ebola

Ebola virus

Caption: Colorized scanning electron micrograph of filamentous Ebola virus particles (blue) budding from a chronically infected VERO E6 cell (yellow-green).
Credit: National Institute of Allergy and Infectious Diseases, NIH

Long before the current outbreak of Ebola Virus Disease (EVD) began in West Africa, NIH-funded scientists had begun collaborating with labs in Sierra Leone and Nigeria to analyze the genomes and develop diagnostic tests for the virus that caused Lassa fever, a deadly hemorrhagic disease related to EVD. But when the outbreak struck in February 2014, an international team led by NIH Director’s New Innovator Awardee Pardis Sabeti quickly switched gears to focus on Ebola.

In a study just out in the journal Science [1], this fast-acting team reported that it has sequenced the complete genetic blueprints, or genomes, of 99 Ebola virus samples obtained from 78 patients in Sierra Leone. This new genomic data has revealed clues about the origin and evolution of the Ebola virus, as well as provided insights that may aid in the development of better diagnostics and inform efforts to devise effective therapies and vaccines.

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