Happy New Year: Looking Back at 2016 Research Highlights

Science Breakthroughs of the Year 2016Happy New Year! While everyone was busy getting ready for the holidays, the journal Science announced its annual compendium of scientific Breakthroughs of the Year. If you missed it, the winner for 2016 was the detection of gravitational waves—tiny ripples in the fabric of spacetime created by the collision of two black holes 1.3 billion years ago! It’s an incredible discovery, and one that Albert Einstein predicted a century ago.

Among the nine other advances that made the first cut for Breakthrough of the Year, several involved the biomedical sciences. As I’ve done in previous years (here and here), I’ll kick off this New Year by taking a quick look of some of the breakthroughs that directly involved NIH support:

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Creative Minds: Breaking Size Barriers in Cryo-Electron Microscopy

Dmitry Lyumkis

Dmitry Lyumkis

When Dmitry Lyumkis headed off to graduate school at The Scripps Research Institute, La Jolla, CA, he had thoughts of becoming a synthetic chemist. But he soon found his calling in a nearby lab that imaged proteins using a technique known as single-particle cryo-electron microscopy (EM). Lyumkis was amazed that the team could take a purified protein, flash-freeze it in liquid nitrogen, and then fire electrons at the protein, capturing the resulting image with a special camera. Also amazing was the sophisticated computer software that analyzed the raw 2D camera images, merging the data and reconstructing it into 3D representations of the protein.

The work was profoundly complex, but Lyumkis thrives on solving extremely difficult puzzles. He joined the Scripps lab to become a structural biologist and a few years later used single-particle cryo-EM to help determine the atomic structure of a key protein on the surface of the human immunodeficiency virus (HIV), the cause of AIDS. The protein had been considered one of the greatest challenges in structural biology and a critical target in developing an AIDS vaccine [1].

Now, Lyumkis has plans to take single-particle cryo-EM to a whole new level—literally. He wants to develop new methods that allow it to model the atomic structures of much smaller proteins. Right now, single-particle cryo-EM has worked with proteins as small as roughly 150 kilodaltons, a measure of a protein’s molecular weight (the approximate average mass of a protein is 53 kDa). Lyumkis plans to drop that number well below 100 kDa, noting that if his new methods work as he hopes, there should be very little, if any, lower size limit to get the technique to work. He envisions generating within a matter of days or weeks the precise structure of an average-sized protein involved in a disease, and then potentially handing it off as an atomic model for drug developers to target for more effective treatment.

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LabTV: Curious about Computer Modeling of Proteins

Josh Carter

In many ways, Josh Carter is a typical college student, with a hectic schedule packed with classes and social activities. But when he enters a structural biology lab at Montana State University in Bozeman, Carter encounters an even faster paced world in which molecular interactions can be measured in femtoseconds—that is, 1 millionth of 1 billionth of 1 second.

Working under the expert eye of principal investigator Blake Wiedenheft, Carter is applying his computational skills to X-ray crystallography data to model the structures of various proteins, as well as to chart their evolution over time and map their highly dynamic interactions with other proteins and molecules. This basic science work is part of this NIH-funded lab’s larger mission to understand how bacteria defend themselves from the viruses that try to infect them. It’s a fascinating area of science with a wide range of potential applications, from treating diseases that arise from imbalances in the microbiome (the communities of microbes that live in and on our bodies) to developing new methods for gene editing and programmable control of gene expression.

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Snapshots of Life: Wild Outcome from Knocking Out Mobility Proteins

Spiky fibroblast cell

Credit: Praveen Suraneni and Rong Li, Stowers Institute for Medical Research

When biologists disabled proteins critical for cell movement, the result was dramatic. The membrane, normally a smooth surface enveloping the cell, erupted in spiky projections. This image, which is part of the Life: Magnified exhibit, resembles a supernova. Although it looks like it exploded, the cell pictured is still alive.

To create the image, Rong Li and Praveen Suraneni, NIH-funded cell biologists at the Stowers Institute for Medical Research in Kansas City, Missouri, disrupted two proteins essential to movement in fibroblasts—connective tissue cells that are also important for healing wounds. The first, called ARPC3, is a protein in the Arp2/3 complex. Without it, the cell moves more slowly and randomly [1]. Inhibiting the second protein gave this cell its spiky appearance. Called myosin IIA (green in the image), it’s like the cell’s muscle, and it’s critical for movement. The blue color is DNA; the red represents a protein called F-actin.

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Creative Minds: Engineering Targeted Breast Cancer Treatments

Photo of Debra Auguste

Debra Auguste

A few years ago, Debra Auguste, a chemical engineer then at Harvard University, was examining the statistics on breast cancer: the second most common cancer in women in the U.S. after lung cancer. She was disturbed to discover that of all the ethnic groups, African American women with breast cancer suffered the highest mortality rates—with 30.8% dying from the disease [1-3].

As an African American woman, Auguste was stunned by this correlation. She wondered whether there was some genetic aspect of breast cancer cells in African Americans that made these cancers more aggressive and more difficult to cure.

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