2017 September
Creative Minds: Mapping the Biocircuitry of Schizophrenia and Bipolar Disorder
Posted on by Dr. Francis Collins
Bruce Yankner
As a graduate student in the 1980s, Bruce Yankner wondered what if cancer-causing genes switched on in non-dividing neurons of the brain. Rather than form a tumor, would those genes cause neurons to degenerate? To explore such what-ifs, Yankner spent his days tinkering with neural cells, using viruses to insert various mutant genes and study their effects. In a stroke of luck, one of Yankner’s insertions encoded a precursor to a protein called amyloid. Those experiments and later ones from Yankner’s own lab showed definitively that high concentrations of amyloid, as found in the brains of people with Alzheimer’s disease, are toxic to neural cells [1].
The discovery set Yankner on a career path to study normal changes in the aging human brain and their connection to neurodegenerative diseases. At Harvard Medical School, Boston, Yankner and his colleague George Church are now recipients of an NIH Director’s 2016 Transformative Research Award to apply what they’ve learned about the aging brain to study changes in the brains of younger people with schizophrenia and bipolar disorder, two poorly understood psychiatric disorders.
Expanding Our View of the Human Microbiome
Posted on by Dr. Francis Collins
Many people still regard bacteria and other microbes just as disease-causing germs. But it’s a lot more complicated than that. In fact, it’s become increasingly clear that the healthy human body is teeming with microorganisms, many of which play essential roles in our metabolism, our immune response, and even our mental health. We are not just an organism, we are a “superorganism” made up of human cells and microbial cells—and the microbes outnumber us! Fueling this new understanding is NIH’s Human Microbiome Project (HMP), a quest begun a decade ago to explore the microbial makeup of healthy Americans.
About 5 years ago, HMP researchers released their first round of data that provided a look at the microbes present in the mouth, gut, nose, and several other parts of the body [1]. Now, their second wave of data, just published in the journal Nature, has tripled this treasure trove of information, promising to further expand our understanding of the human microbiome and its role in health and disease [2]. For example, the new DNA data offer clues as to the functional roles those microbes play and how those can vary over time in different parts of the human body and from one person to the next.
Snapshots of Life: Color Coding the Hippocampus
Posted on by Dr. Francis Collins
Credit: Raunak Basu, University of Utah, Salt Lake City
The final frontier? Trekkies would probably say it’s space, but mapping the brain—the most complicated biological structure in the known universe—is turning out to be an amazing adventure in its own right. Not only are researchers getting better at charting the brain’s densely packed and varied cellular topography, they are starting to identify the molecules that neurons use to connect into the distinct information-processing circuits that allow all walks of life to think and experience the world.
This image shows distinct neural connections in a cross section of a mouse’s hippocampus, a region of the brain involved in the memory of facts and events. The large, crescent-shaped area in green is hippocampal zone CA1. Its highly specialized neurons, called place cells, serve as the brain’s GPS system to track location. It appears green because these neurons express cadherin-10. This protein serves as a kind of molecular glue that likely imparts specific functional properties to this region. [1]
Could Repurposed Asthma Drugs Treat Parkinson’s Disease?
Posted on by Dr. Francis Collins
Thinkstock/ia_64
I had asthma as a child, and I still occasionally develop mild wheezing from exercising in cold air or catching a bad cold. I keep an inhaler on hand for those occasions, as this is a quick and effective way to deliver a medication that opens up those constricted airways. Now, an NIH-supported team has made the surprising discovery that some asthma medicines may also hold the potential to treat or help prevent Parkinson’s disease, a chronic, progressive movement disorder that affects at least a half-million Americans.
The results, published recently in the journal Science, provide yet another example of the tremendous potential of testing drugs originally intended for treating one disease for possible use in others [1]. In this particular instance, researchers screened a library of more than 1,100 well-characterized chemical compounds—including drugs approved by the Food and Drug Administration for treating asthma—to see if they showed any activity against a molecular mechanism known to be involved in Parkinson’s disease.
Creative Minds: Potential Diabetes Lessons from Binge-Eating Snakes
Posted on by Dr. Francis Collins
Stephen Secor/Credit: Secor Lab
Many people would do just about anything to avoid an encounter with a snake. Not Stephen Secor. Growing up in central New York State, Secor was drawn to them. He’d spend hours frolicking through forest and field, flipping rocks and hoping to find one. His animal-loving mother encouraged him to keep looking, and she even let him keep a terrarium full of garter snakes in his bedroom. Their agreement: He must take good care of them—and please make sure they don’t get loose.
As a teen, Secor considered a career as a large-animal veterinarian. But a college zoology course led him right back to his fascination with snakes. Now a professor at the University of Alabama, Tuscaloosa, he’s spent 25 years trying to understand how some snakes, such as the Burmese python shown above, can fast for weeks or even months, and then go on a sudden food binge. Secor’s interest in the feast-or-famine digestive abilities of these snakes has now taken an unexpected turn that he never saw coming: a potential treatment to help people with diabetes.
Protein Links Gut Microbes, Biological Clocks, and Weight Gain
Posted on by Dr. Francis Collins
Caption: Lipids (red) inside mouse intestinal cells with and without NFIL3.
Credit: Lora V. Hooper, University of Texas Southwestern Medical Center, Dallas
The American epidemic of obesity is a major public health concern, and keeping off the extra pounds is a concern for many of us. Yet it can also be a real challenge for people who may eat normally but get their days and nights mixed up, including night-shift workers and those who regularly travel overseas. Why is that?
The most obvious reason is the odd hours throw a person’s 24-hour biological clock—and metabolism—out of sync. But an NIH-funded team of researchers has new evidence in mice to suggest the answer could go deeper to include the trillions of microbes that live in our guts—and, more specifically, the way they “talk” to intestinal cells. Their studies suggest that what gut microbes “say” influences the activity of a key clock-driven protein called NFIL3, which can set intestinal cells up to absorb and store more fat from the diet while operating at hours that might run counter to our fixed biological clocks.
Creative Minds: Exploring the Role of Immunity in Hypertension
Posted on by Dr. Francis Collins
Meena Madhur / Credit: John Russell
If Meena Madhur is correct, people with hypertension will one day pay as much attention to their immune cell profiles as their blood pressure readings. A physician-researcher at Vanderbilt University School of Medicine, Nashville, Madhur is one of a growing number of scientists who thinks the immune system contributes to—or perhaps even triggers—hypertension, which increases the risk of stroke, heart disease, kidney disease, and other serious health problems.
About one of every three adult Americans currently have hypertension, yet a surprising number don’t know they have it and less than half have their high blood pressure under control—leading many health experts to refer to the condition as a “silent killer”[1,2]. For many folks, blood pressure control can be achieved through lifestyle changes, such as losing weight, exercising, limiting salt intake, and taking blood pressure medicines prescribed by their health-care provider. Unfortunately, such measures don’t work for everyone, and some people continue to suffer damage to their kidneys and blood vessels from poorly controlled hypertension.
Madhur wants to know whether the immune system might be playing a role, and whether this might hold some clues for developing new, more targeted ways of treating high blood pressure. To get such answers, this practicing cardiologist will use her 2016 NIH Director’s New Innovator Award to conduct sophisticated, single-cell analyses of the immune systems of people with and without hypertension. Her goal is to produce the most comprehensive catalog to date of which human immune cells might be involved in hypertension.
Robotic Exoskeleton Could Be Right Step Forward for Kids with Cerebral Palsy
Posted on by Dr. Francis Collins
More than 17 million people around the world are living with cerebral palsy, a movement disorder that occurs when motor areas of a child’s brain do not develop correctly or are damaged early in life. Many of those affected were born extremely prematurely and suffered brain hemorrhages shortly after birth. One of the condition’s most common symptoms is crouch gait, which is an excessive bending of the knees that can make it difficult or even impossible to walk. Now, a new robotic device developed by an NIH research team has the potential to help kids with cerebral palsy walk better.
What’s really cool about the robotic brace, or exoskeleton, which you see demonstrated above, is that it’s equipped with computerized sensors and motors that can detect exactly where a child is in the walking cycle—delivering bursts of support to the knees at just the right time. In fact, in a small study of seven young people with crouch gait, the device enabled six to stand and walk taller in their very first practice session!
