In seeking the biological answer to the question of what it means to be human, the brain’s cerebral cortex is a good place to start. This densely folded, outer layer of grey matter, which is vastly larger in Homo sapiens than in other primates, plays an essential role in human consciousness, language, and reasoning.
Now, an NIH-funded team has pinpointed a key set of genes—found only in humans—that may help explain why our species possesses such a large cerebral cortex. Experimental evidence shows these genes prolong the development of stem cells that generate neurons in the cerebral cortex, which in turn enables the human brain to produce more mature cortical neurons and, thus, build a bigger cerebral cortex than our fellow primates.
That sounds like a great advantage for humans! But there’s a downside. Researchers found the same genomic changes that facilitated the expansion of the human cortex may also render our species more susceptible to certain rare neurodevelopmental disorders.
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Tags: autism, Autism Spectrum Disorder, brain, cerebral cortex, cortical neurons, CRISPR/Cas9, DNA sequencing, duplication, evolution, gene-editing technology, genes, genomics, human genome, Human Genome Project, humans, macrocephaly, microcephaly, microdeletion, neurodevelopmental disorders, neurons, neuroscience, Notch, organoids, primates, radial glial stem cells, schizophrenia, signaling genes, stem cells
For centuries, scientists have trained themselves to look through microscopes and carefully study their structural and molecular features. But those long hours bent over a microscope poring over microscopic images could be less necessary in the years ahead. The job of analyzing cellular features could one day belong to specially trained computers.
In a new study published in the journal Cell, researchers trained computers by feeding them paired sets of fluorescently labeled and unlabeled images of brain tissue millions of times in a row . This allowed the computers to discern patterns in the images, form rules, and apply them to viewing future images. Using this so-called deep learning approach, the researchers demonstrated that the computers not only learned to recognize individual cells, they also developed an almost superhuman ability to identify the cell type and whether a cell was alive or dead. Even more remarkable, the trained computers made all those calls without any need for harsh chemical labels, including fluorescent dyes or stains, which researchers normally require to study cells. In other words, the computers learned to “see” the invisible!
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Tags: Alzheimer's disease, brain, Brain Bot, cell biology, cells, computer learning, computers, deep learning, Google, machine learning, microscopy, neurology, neuroscience, Parkinson's disease, schizophrenia
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 .
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.
Tags: aging brain, Alzheimer’s disease, amyloid, bipolar disorder, brain, brain imaging, FISSEQ, fluorescence in situ sequencing of RNA, induced Pluripotent Stem cells, iPSCs, mental illness, NIH Director’s 2016 Transformative Research Award, REST, REST gene, schizophrenia, transcription factor
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.
Tags: 2015 NIH Director’s Transformative Research Award, Autism Spectrum Disorder, bioengineering, brain, brain research, Cpf1, CRISPR, CRISPR-Cas, CRISPR/Cas9, gene editing, gene variants, genomics, laboratory tools, neural organoid, neurobiology, neurological disease, neurological disorders, neurology, optogenetics, organoid, psychiatric disorders, schizophrenia, stem cells
Neuroscientists have been working for a long time to figure out how the human brain works, and that has led many through the years to attempt to map its various regions and create a detailed atlas of their complex geography and functions. While great progress has been made in recent years, existing brain maps have remained relatively blurry and incomplete, reflecting only limited aspects of brain structure or function and typically in just a few people.
In a study reported recently in the journal Nature, an NIH-funded team of researchers has begun to bring this map of the human brain into much sharper focus . By combining multiple types of cutting-edge brain imaging data from more than 200 healthy young men and women, the researchers were able to subdivide the cerebral cortex, the brain’s outer layer, into 180 specific areas in each hemisphere. Remarkably, almost 100 of those areas had never before been described. This new high-resolution brain map will advance fundamental understanding of the human brain and will help to bring greater precision to the diagnosis and treatment of many brain disorders.
Tags: Autism Spectrum Disorder, big data, brain, brain imaging, brain mapping, brain scan, cerebral cortex, connectome, connectomics, fMRI, Functional magnetic resonance imaging, human brain, Human Connectome Project, imaging, neuroimaging, neuroscience, NIH Blueprint for Neuroscience Research, schizophrenia