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.
Credit: Adam Brown and David Biron, University of Chicago
What might appear to be a view inside an unusual kaleidoscope is actually a laboratory plate full of ravenous roundworms (Caenorhabditis elegans) as seen through a microscope. Tens of thousands of worms (black), each about 1 millimeter in length at adulthood, are grazing on a field of bacteria beneath them. The yellow is a jelly-like growth medium called agar that feeds the bacteria, and the orange along the borders was added to enhance the sunburst effect.
The photo was snapped and stylized by NIH training grantee Adam Brown, a fourth-year Ph.D. student in the lab of David Biron at the University of Chicago. Brown uses C. elegans to study the neurotransmitter serotonin, a popular drug target in people receiving treatment for depression and other psychiatric disorders. This tiny, soil-dwelling worm is a go-to model organism for neuroscientists because of its relative simplicity, short life spans, genetic malleability, and complete cell-fate map. By manipulating the different components of the serotonin-signaling system in C. elegans, Brown and his colleagues hope to better understand the most basic circuitry in the central nervous system that underlies decision making, in this case choosing to feed or forage.
While sitting in microbiology class as a college sophomore, Elaine Hsiao was stunned to learn that the human gut held between as much as 6 pounds of bacteria—twice the weight of an adult human brain. She went on to learn during her graduate studies in neurobiology that these microbes had co-evolved with humans and played important roles in our bodies, aiding digestion and immune function, for example. But more intriguing to her, by far, was new research that suggested that gut bacteria might even be influencing our thoughts, moods, and behavior.
Now a senior research fellow at the California Institute of Technology, Hsiao is launching her own effort to explore how these microbes can affect brain function—a very creative endeavor made possible through NIH’s Early Independence Award program—also known as the “skip the postdoc” award.