neurological disease
Creative Minds: Modeling Neurobiological Disorders in Stem Cells
Posted on by Dr. Francis Collins
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.
The Brain: Now You See It, Soon You Won’t
Posted on by Dr. Francis Collins
A post mortem brain is a white, fatty, opaque, three-pound mass. Traditionally scientists have looked inside it by cutting the brain into thin slices, but the relationships and connections of the tens of billions of neurons are then almost impossible to reconstruct. What if we could strip away the fat and study the details of the wiring and the location of specific proteins, in three dimensions? An NIH funded team at Stanford University has done just that, developing a breakthrough method for unmasking the brain.
Using a chemical cocktail, they infuse the brain with a hydrogel that locks in the brain’s form and structure in a type of matrix. Then the fatty layer that coats each nerve cell is stripped away, leaving a transparent brain (check out the transparent mouse brain below). The hydrogel prevents the brain from disintegrating into a puddle once the fat is gone.

Caption: CLARITY transforms a mouse brain at left into a transparent but still intact brain at right. Shown superimposed over a quote from the great Spanish neuroanatomist Ramon y Cajal.
Credit: Kwanghun Chung and Karl Deisseroth, Howard Hughes Medical Institute/Stanford University