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NIH Director’s Transformative Research Award

Creative Minds: Bacteria, Gene Swaps, and Human Cancer

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Julie Dunning Hotopp

Julie Dunning Hotopp

When Julie Dunning Hotopp was a post-doctoral fellow in the early 2000s, bacteria were known for swapping bits of their DNA with other bacteria, a strategy known as lateral gene transfer. But the offloading of genes from bacteria into multicellular organisms was thought to be rare, with limited evidence that a bacterial genus called Wolbachia, which invades the cells of other organisms and takes up permanent residence, had passed off some of its DNA onto a species of beetle and a parasitic worm. Dunning Hotopp wondered whether lateral gene transfer might be a more common phenomenon than the evidence showed.

She and her colleagues soon discovered that Wolbachia had engaged in widespread lateral gene transfer with eight species of insects and nematode worms, possibly passing on genes and traits to their invertebrate hosts [1]. This important discovery put Dunning Hotopp on a research trail that now has taken a sharp turn toward human cancer and earned her a 2015 NIH Director’s Transformative Research Award. This NIH award supports exceptionally innovative research projects that are inherently risky and untested but have the potential to change fundamental research paradigms in areas such as cancer and throughout the biomedical sciences.

Snapshots of Life: A Colorful Look Inside the Retina

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Mapping neurons in the retina

Credit: Amy Robinson, Alex Norton, William Silversmith, Jinseop Kim, Kisuk Lee, Aleks Zlasteski, Matt Green, Matthew Balkam, Rachel Prentki, Marissa Sorek, Celia David, Devon Jones, and Doug Bland, Massachusetts Institute of Technology, Cambridge, MA; Sebastian Seung, Princeton University, Princeton, NJ

This eerie scene might bring back memories of the computer-generated alien war machines from Steven Spielberg’s War of the Worlds thriller. But what you’re seeing is a computer-generated depiction of a quite different world—the world inside the retina, the light-sensitive tissue that lines the back of the eye. The stilt-legged “creatures” are actually ganglion nerve cells, and what appears to be their long “noses” are fibers that will eventually converge to form the optic nerve that relays visual signals to the brain. The dense, multi-colored mat near the bottom of the image is a region where the ganglia and other types of retinal cells interact to convey visual information.

What I find particularly interesting about this image is that it was produced through the joint efforts of people who played EyeWire, an internet crowdsourcing game developed in the lab of computational neuroscientist Sebastian Seung, now at Princeton University in New Jersey.  Seung and his colleagues created EyeWire using a series of high-resolution microscopic images of the mouse retina, which were digitized into 3D cubes containing dense skeins of branching nerve fibers. It’s at this point where the crowdsourcing came in. Online gamers—most of whom aren’t scientists— volunteered for a challenge that involved mapping the 3D structure of individual nerve cells within these 3D cubes. Players literally colored-in the interiors of the cells and progressively traced their long extensions across the image to distinguish them from their neighbors. Sounds easy, but the branches are exceedingly thin and difficult to follow.

Diaper Compound Brings Change to Cell Microscopy

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Traditional vs. Expansion Microscopy

Caption: Mouse brain tissue as viewed by traditional microscopy (left) and expansion microscopy (right), which makes it possible to visualize individual synapses (example in white box). In both views, green indicates neurons; blue, pre-synaptic proteins; and red, post-synaptic proteins.
Credit: Ed Boyden, Fei Chen, Paul Tillberg, MIT

Light microscopy has been a mainstay of neuroscience and many areas of biology for more than a century. But the resolution limit of light, based on immutable physical principles, has kept the fine details of many structures out of view. Scientists can’t change the laws of physics—but NIH-supported researchers recently devised a highly creative way to see images that were previously out of reach, by expanding the contents of tissue sections up to five times their normal size, while maintaining the anatomic arrangements. The new approach takes advantage of a compound used in—get this—disposable diapers!

By harnessing the super-absorbent properties of sodium polyacrylate, a polymer commonly used in diapers, a team from the Massachusetts Institute of Technology (MIT) developed a new technique that makes it possible for conventional microscopes to produce super high-resolution images of brain cells. The name of the new technique? Expansion microscopy.