Creative Minds: Rapid Testing for Antibiotic Resistance

Ahmad Khalil

Ahmad (Mo) Khalil

The term “freeze-dried” may bring to mind those handy MREs (Meals Ready to Eat) consumed by legions of soldiers, astronauts, and outdoor adventurers. But if one young innovator has his way, a test that features freeze-dried biosensors may soon be a key ally in our nation’s ongoing campaign against the very serious threat of antibiotic-resistant bacterial infections.

Each year, antibiotic-resistant infections account for more than 23,000 deaths in the United States. To help tackle this challenge, Ahmad (Mo) Khalil, a researcher at Boston University, recently received an NIH Director’s New Innovator Award to develop a system that can more quickly determine whether a patient’s bacterial infection will respond best to antibiotic X or antibiotic Y—or, if the infection is actually viral rather than bacterial, no antibiotics are needed at all.

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Creative Minds: Studying the Human Genome in 3D

Jesse Dixon

Jesse Dixon

As a kid, Jesse Dixon often listened to his parents at the dinner table discussing how to run experiments and their own research laboratories. His father Jack is an internationally renowned biochemist and the former vice president and chief scientific officer of the Howard Hughes Medical Institute. His mother Claudia Kent Dixon, now retired, did groundbreaking work in the study of lipid molecules that serve as the building blocks of cell membranes.

So, when Jesse Dixon set out to pursue a career, he followed in his parents’ footsteps and chose science. But Dixon, a researcher at the Salk Institute, La Jolla, CA, has charted a different research path by studying genomics, with a focus on understanding chromosomal structure. Dixon has now received a 2016 NIH Director’s Early Independence Award to study the three-dimensional organization of the genome, and how changes in its structure might contribute to diseases such as cancer or even to physical differences among people.

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Aging Research: Plasma Protein Revitalizes the Brain

Elixir of youth?For centuries, people have yearned for an elixir capable of restoring youth to their aging bodies and minds. It sounds like pure fantasy, but, in recent years, researchers have shown that the blood of young mice can exert a regenerative effect when transfused into older animals. Now, one of the NIH-funded teams that brought us those exciting findings has taken an early step toward extending them to humans.

In their latest work published in Nature, the researchers showed that blood plasma collected from the umbilical cords of newborn infants possesses some impressive rejuvenating effects [1]. When the human plasma was infused into the bloodstream of old mice, it produced marked improvements in learning and memory. Additional experiments traced many of those cognitive benefits to a specific protein called TIMP2—an unexpected discovery that could pave the way for the development of brain-boosting drugs to slow the effects of aging.

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Missing Genes Point to Possible Drug Targets

Human knockout projectEvery person’s genetic blueprint, or genome, is unique because of variations that occasionally occur in our DNA sequences. Most of those are passed on to us from our parents. But not all variations are inherited—each of us carries 60 to 100 “new mutations” that happened for the first time in us. Some of those variations can knock out the function of a gene in ways that lead to disease or other serious health problems, particularly in people unlucky enough to have two malfunctioning copies of the same gene. Recently, scientists have begun to identify rare individuals who have loss-of-function variations that actually seem to improve their health—extraordinary discoveries that may help us understand how genes work as well as yield promising new drug targets that may benefit everyone.

In a study published in the journal Nature, a team partially funded by NIH sequenced all 18,000 protein-coding genes in more than 10,500 adults living in Pakistan [1]. After finding that more than 17 percent of the participants had at least one gene completely “knocked out,” researchers could set about analyzing what consequences—good, bad, or neutral—those loss-of-function variations had on their health and well-being.

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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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