Snapshots of Life: Making Sense of Smell

Modified rendering of mouse olfactory bulb

Credit: Jeremy McIntyre, University of Florida College of Medicine, Gainesville

You’ve probably learned the hard way about how the grocery list can go out the window when you go shopping on an empty stomach. Part of the reason is that our sense of smell intensifies when we’re hungry, making the aroma of freshly baked cookies, fried chicken, and other tempting goodies even more noticeable. And this beautiful micrograph helps to provide a biological explanation for this phenomenon.

The image, which looks like something that Van Gogh might have painted, shows a thick mesh of neurons in a small cross section of a mouse’s olfactory bulb, a structure located in the forebrain of all vertebrates (including humans!) that processes input about odors detected by the nose. Here, you see specialized neurons called mitral cells (red) that can receive signals from the hypothalamus, a brain region known for its role in hunger and energy balance. Also fluorescently labeled are receptors that detect acetylcholine signals from the brain (green) and the nuclei of all cells in the olfactory bulb (blue).

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Finding Brain Circuits Tied to Alertness

Everybody knows that it’s important to stay alert behind the wheel or while out walking on the bike path. But our ability to react appropriately to sudden dangers is influenced by whether we feel momentarily tired, distracted, or anxious. How is it that the brain can transition through such different states of consciousness while performing the same routine task, even as its basic structure and internal wiring remain unchanged?

A team of NIH-funded researchers may have found an important clue in zebrafish, a popular organism for studying how the brain works. Using a powerful new method that allowed them to find and track brain circuits tied to alertness, the researchers discovered that this mental state doesn’t work like an on/off switch. Rather, alertness involves several distinct brain circuits working together to bring the brain to attention. As shown in the video above that was taken at cellular resolution, different types of neurons (green) secrete different kinds of chemical messengers across the zebrafish brain to affect the transition to alertness. The messengers shown are: serotonin (red), acetylcholine (blue-green), and dopamine and norepinephrine (yellow).

What’s also fascinating is the researchers found that many of the same neuronal cell types and brain circuits are essential to alertness in zebrafish and mice, despite the two organisms being only distantly related. That suggests these circuits are conserved through evolution as an early fight-or-flight survival behavior essential to life, and they are therefore likely to be important for controlling alertness in people too. If correct, it would tell us where to look in the brain to learn about alertness not only while doing routine stuff but possibly for understanding dysfunctional brain states, ranging from depression to post-traumatic stress disorder (PTSD).

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Creative Minds: Building a CRISPR Gene Drive Against Malaria

Valentino Gantz

Valentino Gantz/Credit: Erik Jepsen

Researchers have used Drosophila melanogaster, the common fruit fly that sometimes hovers around kitchens, to make seminal discoveries involving genetics, the nervous system, and behavior, just to name a few. Could a new life-saving approach to prevent malaria be next? Valentino Gantz, a researcher at the University of California, San Diego, is on a path to answer that question.

Gantz has received a 2016 NIH Director’s Early Independence Award to use Drosophila to hone a new bioengineered tool that acts as a so-called “gene drive,” which spreads a new genetically encoded trait through a population much faster than would otherwise be possible. The lessons learned while working with flies will ultimately be applied to developing a more foolproof system for use in mosquitoes with the hope of stopping the transmission of malaria and potentially other serious mosquito-borne diseases.

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Can Artificial Cells Take Over for Lost Insulin-Secreting Cells?

artificial beta cells

Caption: Artificial beta cell, made of a lipid bubble (purple) carrying smaller, insulin-filled vesicles (green). Imaged with cryo-scanning electron microscope (cryo-SEM) and colorized.
Credit: Zhen Gu Lab

People with diabetes have benefited tremendously from advances in monitoring and controlling blood sugar, but they’re still waiting and hoping for a cure. Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is deficient in diabetes. The latest strategy of this kind is called AβCs, short for artificial beta cells.

As you see in the cryo-SEM image above, AβCs are specially designed lipid bubbles, each of which contains hundreds of smaller, ball-like vesicles filled with insulin. The AβCs are engineered to “sense” a rise in blood glucose, triggering biochemical changes in the vesicle and the automatic release of some of its insulin load until blood glucose levels return to normal.

In recent studies of mice with type 1 diabetes, researchers partially supported by NIH found that a single injection of AβCs under the skin could control blood glucose levels for up to five days. With additional optimization and testing, the hope is that people with diabetes may someday be able to receive AβCs through patches that painlessly stick on their skin.

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Creative Minds: A New Way to Look at Cancer

Bradley Bernstein

Bradley Bernstein

Inside our cells, strands of DNA wrap around spool-like histone proteins to form a DNA-histone complex called chromatin. Bradley Bernstein, a pathologist at Massachusetts General Hospital, Harvard University, and Broad Institute, has always been fascinated by this process. What interests him is the fact that an approximately 6-foot-long strand of DNA can be folded and packed into orderly chromatin structures inside a cell nucleus that’s just 0.0002 inch wide.

Bernstein’s fascination with DNA packaging led to the recent major discovery that, when chromatin misfolds in brain cells, it can activate a gene associated with the cancer glioma [1]. This suggested a new cancer-causing mechanism that does not require specific DNA mutations. Now, with a 2016 NIH Director’s Pioneer Award, Bernstein is taking a closer look at how misfolded and unstable chromatin can drive tumor formation, and what that means for treating cancer.

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