All plants and animals are susceptible to viral infections. But did you know that’s also true for bacteria? They get nailed by viruses called bacteriophages, and there are thousands of them in nature including this one that resembles a lunar lander: bacteriophage T4 (left panel). It’s a popular model organism that researchers have studied for nearly a century, helping them over the years to learn more about biochemistry, genetics, and molecular biology .
The bacteriophage T4 infects the bacterium Escherichia coli, which normally inhabits the gastrointestinal tract of humans. T4’s invasion starts by touching down on the bacterial cell wall and injecting viral DNA through its tube-like tail (purple) into the cell. A DNA “packaging machine” (middle and right panels) between the bacteriophage’s “head” and “tail” (green, yellow, blue spikes) keeps the double-stranded DNA (middle panel, red) at the ready. All the vivid colors you see in the images help to distinguish between the various proteins or protein subunits that make up the intricate structure of the bacteriophage and its DNA packaging machine.
Posted In: Snapshots of Life
Tags: bacteria, bacteriophage, cancer, Chimera Visualization Software, cryo-electron microscopy, cryo-EM, E. coli, Escherichia coli, FASEB Bioart 2017, HIV, structural biology, T4 bacteriophage, virus, x-ray crystallography
For nearly 20 years, Hao Wu has studied innate immunity, our body’s first line of defense against infection. One of her research specialties is the challenging technique of X-ray crystallography, which she uses to capture the atomic structure of key molecules that drive an inflammatory response. But for this method to work, the proteins have to be coaxed to form regular crystals—and that has often proven to be prohibitively difficult. Wu, now at Boston Children’s Hospital and Harvard Medical School, can be relentless in her attempts to crystallize difficult molecular structures, and this quality has helped her make a number of important discoveries. Among them is the seminal finding that innate immune cells process and internalize signals to handle invading microbes much differently than previously thought.
Innate immune cells, which include macrophages and neutrophils, patrol the body non-specifically, keeping a look out for signs of anything unusual. Using protein receptors displayed on their surfaces, these cells can sense distinctive molecular patterns on microbes, prompting an immediate response at the site of infection.
Wu has shown that these cells form previously unknown protein complexes that mediate the immune response [1, 2]. She received an NIH Director’s 2015 Pioneer Award to help translate her expertise in the structural biology of these signaling complexes into the design of new kinds of anti-inflammatory treatments. This award helps exceptionally creative scientists to pioneer transformative approaches to major challenges in biomedical and behavioral research.
Tags: Alzheimer’s disease, anti-inflammatory treatment, ASC, cell signaling, chronic inflammation, cryo-EM, gout, immune response, immunology, inflammation, innate immunity, lymphoma, NIH Director’s 2015 Pioneer Award, NIH Pioneer Award, signalosome, SMOCs, structural immunology, supramolecular organizing centers, x-ray crystallography
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.
In the quest to find faster, better ways of mapping the structure of proteins and other key biological molecules, a growing number of researchers are turning to an innovative method that pushes the idea of a freeze frame to a whole new level: cryo-electron microscopy (cryo-EM). The technique, which involves flash-freezing molecules in liquid nitrogen and bombarding them with electrons to capture their images with a special camera, has advanced dramatically since its inception thanks to the efforts of many creative minds. In fact, cryo-EM has improved so much that its mapping performance now rivals that of X-ray crystallography , the long-time workhorse of drug developers and structural biologists.
To get an idea of just how far cryo-EM has come over the last decade, take a look at the composite image above, which shows a bacterial enzyme (beta-galactosidase) bound to a drug-like molecule (phenylethyl beta-D-thiogalactopyranoside). To the left, you see a blob-like area generated by cryo-EM methods that would have been considered state-of-the-art just a few years ago. To the right, there’s an exquisitely detailed structure, which was produced at more than 10-times greater resolution using the latest advances in cryo-EM. In fact, today’s cryo-EM is so powerful that researchers can almost make out individual atoms! Very impressive, and just one of the many reasons why the journal Nature Methods recently named cryo-EM its “Method of the Year” for 2015 .
Tags: 3D imaging, Alzheimer’s disease, beta-galactosidase, computational methods, cryo, cryo-electron microscopy, cryo-EM, drug discovery, electron microscopy, electrons, HIV, imaging, imaging method, Method of the Year, microscopy, molecules, NMR, nuclear magnetic resonance spectroscopy, phenylethyl beta-D-thiogalactopyranoside, protein maps, protein structures, small molecules, x-ray crystallography