Creative Minds: A Transcriptional “Periodic Table” of Human Neurons

neuronal cell

Caption: Mouse fibroblasts converted into induced neuronal cells, showing neuronal appendages (red), nuclei (blue) and the neural protein tau (yellow).
Credit: Kristin Baldwin, Scripps Research Institute, La Jolla, CA

Writers have The Elements of Style, chemists have the periodic table, and biomedical researchers could soon have a comprehensive reference on how to make neurons in a dish. Kristin Baldwin of the Scripps Research Institute, La Jolla, CA, has received a 2016 NIH Director’s Pioneer Award to begin drafting an online resource that will provide other researchers the information they need to reprogram mature human skin cells reproducibly into a variety of neurons that closely resemble those found in the brain and nervous system.

These lab-grown neurons could be used to improve our understanding of basic human biology and to develop better models for studying Alzheimer’s disease, autism, and a wide range of other neurological conditions. Such questions have been extremely difficult to explore in mice and other animal models because they have shorter lifespans and different brain structures than humans.

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All Scientific Hands on Deck to End the Opioid Crisis

Word cloudIn 2015, 2 million people had a prescription opioid-use disorder and 591,000 suffered from a heroin-use disorder; prescription drug misuse alone cost the nation $78.5 billion in healthcare, law enforcement, and lost productivity. But while the scope of the crisis is staggering, it is not hopeless.

We understand opioid addiction better than many other drug use disorders; there are effective strategies that can be implemented right now to save lives and to prevent and treat opioid addiction. At the National Rx Drug Abuse and Heroin Summit in Atlanta last April, lawmakers and representatives from health care, law enforcement, and many private stakeholders from across the nation affirmed a strong commitment to end the crisis.

Research will be a critical component of achieving this goal. Today in the New England Journal of Medicine, we laid out a plan to accelerate research in three crucial areas: overdose reversal, addiction treatment, and pain management [1].

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Creative Minds: Modeling Neurobiological Disorders in Stem Cells

Feng Zhang

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.

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LabTV: Curious About a Mother’s Bond

Bianca JonesThe bond between a mother and her child is obviously very special. That’s true not only in humans, but in mice and other animals that feed and care for their young. But what exactly goes on in the brain of a mother when she hears her baby crying? That’s one of the fascinating questions being explored by Bianca Jones Marlin, the young neuroscience researcher featured in this LabTV video.

Currently a postdoctoral fellow at New York University School of Medicine, Marlin is particularly interested in the influence of a hormone called oxytocin, popularly referred to as the “love hormone,” on maternal behaviors. While working on her Ph.D.in the lab of Robert Froemke, Marlin tested the behavior and underlying brain responses of female mice—both mothers and non-mothers—upon hearing distress cries of young mice, which are called pups. She also examined how those interactions changed with the addition of oxytocin.

I’m pleased to report that the results of the NIH-funded work Marlin describes in her video appeared recently in the highly competitive journal Nature [1]. And what she found might strike a chord with all the mothers out there. Her studies show that oxytocin makes key portions of the mouse brain more sensitive to the cries of the pups, almost as if someone turned up the volume.

In fact, when Marlin and her colleagues delivered oxytocin to the brains (specifically, the left auditory cortexes) of mice with no pups of their own, they responded like mothers themselves! Those childless mice quickly learned to perk up and fetch pups in distress, returning them to the safety of their nests.

Marlin says her interest in neuroscience arose from her experiences growing up in a foster family. She witnessed some of her foster brothers and sisters struggling with school and learning. As an undergraduate at Saint John’s University in Queens, NY, she earned a dual bachelor’s degree in Biology and Adolescent Education before getting her license to teach 6th through 12th grade Biology. But Marlin soon decided she could have a greater impact by studying how the brain works and gaining a better understanding of the biological mechanisms involved in learning, whether in the classroom or through life experiences, such as motherhood.

Marlin welcomes the opportunity that the lab gives her to “be an explorer”—to ask deep, even ethereal, questions and devise experiments aimed at answering them. “That’s the beauty of science and research,” she says. “To be able to do that the rest of my life? I’d be very happy.”

References:

[1] Oxytocin enables maternal behaviour by balancing cortical inhibition. Marlin BJ, Mitre M, D’amour JA, Chao MV, Froemke RC. Nature. 2015 Apr 23;520(7548):499-504.

Links:

LabTV

Froemke Lab (NYU Langone)

Science Careers (National Institute of General Medical Sciences/NIH)

Careers Blog (Office of Intramural Training/NIH)

Scientific Careers at NIH