optogenetics
Creative Minds: Modeling Neurobiological Disorders in Stem Cells
Posted on by Dr. Francis Collins
Feng Zhang
Most neurological and psychiatric disorders are profoundly complex, involving a variety of environmental and genetic factors. Researchers around the world have worked with patients and their families to identify hundreds of possible genetic leads to learn what goes wrong in autism spectrum disorder, schizophrenia, and other conditions. The great challenge now is to begin examining this growing cache of information more systematically to understand the mechanism by which these gene variants contribute to disease risk—potentially providing important information that will someday lead to methods for diagnosis and treatment.
Meeting this profoundly difficult challenge will require a special set of laboratory tools. That’s where Feng Zhang comes into the picture. Zhang, a bioengineer at the Broad Institute of MIT and Harvard, Cambridge, MA, has made significant contributions to a number of groundbreaking research technologies over the past decade, including optogenetics (using light to control brain cells), and CRISPR/Cas9, which researchers now routinely use to edit genomes in the lab [1,2].
Zhang has received a 2015 NIH Director’s Transformative Research Award to develop new tools to study multiple gene variants that might be involved in a neurological or psychiatric disorder. Zhang draws his inspiration from nature, and the microscopic molecules that various organisms have developed through the millennia to survive. CRISPR/Cas9, for instance, is a naturally occurring bacterial defense system that Zhang and others have adapted into a gene-editing tool.
Snapshots of Life: Making the Brain Transparent
Posted on by Dr. Francis Collins
Credit: Ken Chan and Viviana Gradinaru Group, Caltech
What you are looking at above is something scientists couldn’t even dream of imaging less than a decade ago: bundles of neurons in the brainstem of an adult mouse. These bundles are randomly labeled with various colors that enable researchers to trace the course of each as it projects from the brainstem areas to other parts of the brain. Until recently, such a view would have been impossible because, like other organs, the brain is opaque and had to be sliced into thin, transparent sections of tissue to be examined under a light microscope. These sections forced a complex 3D structure to be visualized in 2D, losing critical detail about the connections.
But now, researchers have developed innovative approaches to make organs and other large volumes of tissue transparent when viewed with standard light microscopy [1]. This particular image was made using the Passive CLARITY Technique, or PACT, developed by the NIH-supported lab of Viviana Gradinaru at the California Institute of Technology (Caltech), Pasadena. Gradinaru has been working on turning tissues transparent since 2010, starting as a graduate student in the lab of CLARITY developer and bioengineering pioneer Karl Deisseroth at Stanford University. PACT is her latest refinement of the concept.
Tracing the Neural Circuitry of Appetite
Posted on by Dr. Francis Collins
Credit: Michael Krashes, NIDDK, NIH
If you’ve ever skipped meals for a whole day or gone on a strict, low-calorie diet, you know just how powerful the feeling of hunger can be. Your stomach may growl and rumble, but, ultimately, it’s your brain that signals when to start eating—and when to stop. So, learning more about the brain’s complex role in controlling appetite is crucial to efforts to develop better ways of helping the millions of Americans afflicted with obesity [1].
Thanks to recent technological advances that make it possible to study the brain’s complex circuitry in real-time, a team of NIH-funded researchers recently made some important progress in understanding the neural basis for appetite. In a study published in the journal Nature Neuroscience, the researchers used a variety of innovative techniques to control activity in the brains of living mice, and identified one particular circuit that appears to switch hunger off and on [2].
NIH-Funded Research Makes Science’s “Top 10” List
Posted on by Dr. Francis Collins
Modeled after Time’s Person of the Year, the journal Science has a tradition of honoring the year’s most groundbreaking research advances. For 2014, the European Space Agency nabbed first place with the Rosetta spacecraft’s amazing landing on a comet. But biomedical science also was well represented on the “Top 10” list—with NIH helping to support at least four of the advances. So, while I’ve highlighted some of these in the past, I can’t think of a better way for the NIH Director to ring in the New Year than to take a brief look back at these remarkable achievements!
Youth serum for real? Spanish explorer Ponce de Leon may have never discovered the Fountain of Youth, but researchers have engineered an exciting new lead. Researchers fused the circulatory systems of young and old mice to create a shared blood supply. In the old mice, the young blood triggered new muscle and more neural connections, and follow-up studies revealed that their memory formation improved. The researchers discovered that a gene called Creb prompts the rejuvenation. Block the protein produced by Creb, and the young blood loses its anti-aging magic [1]. Another team discovered that a factor called GDF11 increased the number of neural stem cells and stimulated the growth of new blood vessels in the brains of older animals [2].
Creative Minds: Trying to Curb Those Sugar Cravings
Posted on by Dr. Francis Collins
It’s that time of year again: holiday parties and family feasts! One of the most frequently made—and most often broken—New Year’s resolutions is to follow a sensible diet. All goes well until you catch sight of a cupcake or smell some cookies fresh out of the oven. Sensory cues trigger cravings that crumble resolve and, before you know it, you’re on a sugar high.
Actually, from a biological perspective, it’s not a fair fight. Once desires and preferences are hard-wired in the brain, people have difficulty changing their habits. But one of 2013 recipients of the NIH Director’s New Innovator Award, Kay Tye of the Massachusetts Institute of Technology (MIT), Cambridge, MA, is up for the challenge. In a high-risk, high-reward research project, she’s trying to find ways to control food cravings by reprogramming the brain, where the behavior begins.
Creative Minds: Lighting Up Memory
Posted on by Dr. Francis Collins
One of the most debilitating, and heartbreaking, consequences of Alzheimer’s disease is the way it slowly robs people of their memories. Unfortunately, we don’t yet have a cure for Alzheimer’s, let alone a good understanding of exactly how this disease destroys memory skills. That’s why, in this first post in my series highlighting some of the awardees in NIH Common Fund’s High-Risk, High-Reward Research Program, I’m excited to introduce a young scientist who’s using some cool technology to tackle this formidable challenge: Christine Ann Denny.
A winner of a 2013 NIH Director’s Early Independence Awards (often called the “skip-the-postdoc” award), Denny has developed a technique to label the cells that encode individual memories in the brains of mice. That’s right: she tags the nerve cells that build these memories, the neurons, with a fluorescent molecule that glows.
Driving Innovation and Creativity with High Risk Research
Posted on by Dr. Francis Collins
Caption: One of the many faces of NIH-supported innovation, Stanford’s Christina Smolke is exploring how synthetic biology and microbes can be used to produce new drugs. She is a 2012 Pioneer Award winner.
Credit: Linda Cicero/Stanford News Service
High-risk research isn’t for the faint of heart. It’s for fearless researchers who envision and develop innovative projects with unconventional approaches that, if successful, may yield great leaps in our understanding of health problems and/or biological mechanisms. It takes nerve and creativity to conceive such projects—and, often, special support to bring them to fruition. And, as the name implies, there is a significant chance of failure.
Shining a Bright Light on Cocaine Addiction
Posted on by Dr. Francis Collins
Caption: Optogenetic stimulation using laser pulses lights up the prelimbic cortex
Source: Courtesy of Billy Chen and Antonello Bonci
Wow—there is a lot of exciting brain research in progress, and this week is no exception. A team here at NIH, collaborating with scientists at the University of California in San Francisco, delivered harmless pulses of laser light to the brains of cocaine-addicted rats, blocking their desire for the narcotic.
If that sounds a bit way out, I can assure you the approach is based on some very solid evidence suggesting that people—and rats—are more vulnerable to addiction when a region of their brain in the prefrontal cortex isn’t functioning properly. Brain imaging studies show that rat and human addicts have less activity in the region compared with healthy individuals; and chronic cocaine use makes the problem of low activity even worse. The prefrontal cortex is critical for decision-making, impulse control, and behavior; it helps you weigh the negative consequences of drug use.
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