The three neurons (red) visible in this image were derived from human embryonic stem cells. Undifferentiated stem cells are green here. Image and caption information courtesy of the California Institute for Regenerative Medicine.

This slide shows the technologies that the Joint Center for Structural Genomics developed for going from gene to structure and how the technologies have been integrated into a high-throughput pipeline, including all of the steps from target selection, parallel expression, protein purification, automated crystallization trials, automated crystal screening, structure determination, validation, and publication.

The photo shows a confocal microscopy image of perineuronal nets (PNNs), which are specialized extracellular matrix (ECM) structures in the brain. The PNN surrounds some nerve cells in brain regions including the cortex, hippocampus and thalamus. Researchers study the PNN to investigate their involvement stabilizing the extracellular environment and forming nets around nerve cells and synapses in the brain. Abnormalities in the PNNs have been linked to a variety of disorders, including epilepsy and schizophrenia, and they limit a process called neural plasticity in which new nerve connections are formed. To visualize the PNNs, researchers labeled them with Wisteria floribunda agglutinin (WFA)-fluorescein. Related to image 3741.

A crystal of rabbit GPDA protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

Muscles stretch and contract when we walk, and skin splits open and knits back together when we get a paper cut. To study these contractile forces, researchers built a three-dimensional scaffold that mimics tissue in an organism. Researchers poured a mixture of cells and elastic collagen over microscopic posts in a dish. Then they studied how the cells pulled and released the posts as they formed a web of tissue. To measure forces between posts, the researchers developed a computer model. Their findings--which show that contractile forces vary throughout the tissue--could have a wide range of medical applications.

This video shows the structure of the pore-forming protein VDAC-1 from humans. This molecule mediates the flow of products needed for metabolism--in particular the export of ATP--across the outer membrane of mitochondria, the power plants for eukaryotic cells. VDAC-1 is involved in metabolism and the self-destruction of cells--two biological processes central to health.

Related to videos 2570 and 2571.

Animation for the vesicular shuttle model of Golgi transport.

Some children are born with a mutation in a regulatory site on this enzyme that causes them to over-secrete insulin when they consume protein. We found that a compound from green tea (shown in the stick figure and by the yellow spheres on the enzyme) is able to block this hyperactivity when given to animals with this disorder.

Ecteinascidin 743 (ET-743, brand name Yondelis), was discovered and isolated from a sea squirt, Ecteinascidia turbinata, by NIGMS grantee Kenneth Rinehart at the University of Illinois. It was synthesized by NIGMS grantees E.J. Corey and later by Samuel Danishefsky. Multiple versions of this structure are available as entries 2790-2797.

Student Christina Hueneke of the Midwest Center for Structural Genomics is overseeing a protein cloning robot. The robot was designed as part of an effort to exponentially increase the output of a traditional wet lab. Part of the center's goal is to cut the average cost of analyzing a protein from $200,000 to $20,000 and to slash the average time from months to days and hours.

Microfluidic chips have many uses in biology labs. The one shown here was used by bioengineers to study bacteria, allowing the researchers to synchronize their fluorescing so they would blink in unison. Related to images 3266 and 3268. From a UC San Diego news release, "Researchers create living 'neon signs' composed of millions of glowing bacteria."

A computer model shows how the endoplasmic reticulum is close to and almost wraps around mitochondria in the cell. The endoplasmic reticulum is lime green and the mitochondria are yellow. This image relates to a July 27, 2009 article in Computing Life.

This animation shows the effect of exposure to hypochlorous acid, which is found in certain types of immune cells, on bacterial proteins. The proteins unfold and stick to one another, leading to cell death.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. This image shows how luciferase-based imaging could be used to visualize the heart for regeneration studies (left), or label all tissues for stem cell transplantation (right).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.

Two highly stressed osteosarcoma cells are shown with a set of green droplet-like structures followed by a second set of magenta droplets. These droplets are composed of fluorescently labeled stress-response proteins, either G3BP or UBQLN2 (Ubiquilin-2). Each protein is undergoing a fascinating process, called phase separation, in which a non-membrane bound compartment of the cytoplasm emerges with a distinct environment from the surrounding cytoplasm. Subsequently, the proteins fuse with like proteins to form larger droplets, in much the same way that raindrops merge on a car’s windshield.

Human embryonic stem cells were differentiated into cells like those found in the pancreas (blue), which give rise to insulin-producing cells (red). When implanted in mice, the stem cell-derived pancreatic cells can replace the insulin that isn't produced in type 1 diabetes. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Stereo triplet of a sea urchin embryo stained to reveal actin filaments (orange) and microtubules (blue). This image is part of a series of images: 1047, 1048, 1049, 1050 and 1052.

Phenylalanine tRNA showing the anticodon (yellow) and the amino acid, phenylalanine (blue and red spheres).

Bacillus anthracis (anthrax) cells being killed by a fluorescent trans-translation inhibitor, which disrupts bacterial protein synthesis. The inhibitor is naturally fluorescent and looks blue when it is excited by ultraviolet light in the microscope. This is a black-and-white version of Image 3525.

Researchers use cluster analysis to study protein shape and function. Each green circle represents one potential shape of the protein mitoNEET. The longer the blue line between two circles, the greater the differences between the shapes. Most shapes are similar; they fall into three clusters that are represented by the three images of the protein. From a Rice University news release. Graduate student Elizabeth Baxter and Patricia Jennings, professor of chemistry and biochemistry at UCSD, collaborated with José Onuchic, a physicist at Rice University, on this work.

A light microscope image of a cell from the endosperm of an African globe lily (Scadoxus katherinae). This is one frame of a time-lapse sequence that shows cell division in action. The lily is considered a good organism for studying cell division because its chromosomes are much thicker and easier to see than human ones. Staining shows microtubules in red and chromosomes in blue. Here, condensed chromosomes are clearly visible near the end of a round of mitosis.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1019, and 1021.

By mixing fluorescent dyes like an artist mixes paints, scientists are able to color code individual chromosomes. The technique, abbreviated multicolor-FISH, allows researchers to visualize genetic abnormalities often linked to disease. In this image, "painted" chromosomes from a person with a hereditary disease called Werner Syndrome show where a piece of one chromosome has fused to another (see the gold-tipped maroon chromosome in the center). As reported by molecular biologist Jan Karlseder of the Salk Institute for Biological Studies, such damage is typical among people with this rare syndrome.

A combination of protein structures determined experimentally and computationally shows us the complete metabolic network of a heat-loving bacterium.

A 20-µm thick section of mouse midbrain. The nerve cells are transparent and weren’t stained. Instead, the color is generated by interaction of white polarized light with the molecules in the cells and indicates their orientation.

The image was obtained with a polychromatic polarizing microscope that shows the polychromatic birefringent image with hue corresponding to the slow axis orientation. More information about the microscopy that produced this image can be found in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak.

A crystal of bovine milk alpha-lactalbumin protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

Antibiotic resistance in microbes is a serious health concern. So researchers have turned their attention to how bacteria undo the action of some antibiotics. Here, scientists set out to find the conditions that help individual bacterial cells survive in the presence of the antibiotic rifampicin. The research team used Mycobacterium smegmatis, a more harmless relative of Mycobacterium tuberculosis, which infects the lung and other organs and causes serious disease.

In this image, genetically identical mycobacteria are growing in a miniature growth chamber called a microfluidic chamber. Using live imaging, the researchers found that individual mycobacteria will respond differently to the antibiotic, depending on the growth stage and other timing factors. The researchers used genetic tagging with green fluorescent protein to distinguish cells that can resist rifampicin and those that cannot. With this gene tag, cells tolerant of the antibiotic light up in green and those that are susceptible in violet, enabling the team to monitor the cells' responses in real time.

To learn more about how the researchers studied antibiotic resistance in mycobacteria, see this news release from Tufts University. Related to video 5752.

Cilia (cilium in singular) are complex molecular machines found on many of our cells. One component of cilia is the doublet microtubule, a major part of cilia’s skeletons that give them support and shape. This animated video illustrates the structure of doublet microtubules, which contain 451 protein chains that were mapped using cryo-electron microscopy. Image can be found here 6548.

This image shows a computer-generated, three-dimensional map of the rotavirus structure. This virus infects humans and other animals and causes severe diarrhea in infants and young children. By the age of five, almost every child in the world has been infected with this virus at least once. Scientists have found a vaccine against rotavirus, so in the United States there are very few fatalities, but in developing countries and in places where the vaccine is unavailable, this virus is responsible for more than 200,000 deaths each year.

The rotavirus comprises three layers: the outer, middle and inner layers. On infection, the outer layer is removed, leaving behind a "double-layered particle." Researchers have studied the structure of this double-layered particle with a transmission electron microscope. Many images of the virus at a magnification of ~50,000x were acquired, and computational analysis was used to combine the individual particle images into a three-dimensional reconstruction.

The image was rendered by Melody Campbell (PhD student at TSRI). Work that led to the 3D map was published in Campbell et al. Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure. 2012;20(11):1823-8. PMCID: PMC3510009.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3415, 3417, 3418, and 3419.

These neurons were derived from human embryonic stem cells. The neural cell bodies with axonal projections are visible in red, and the nuclei in blue. Some of the neurons have become dopaminergic neurons (yellow), the type that degenerate in people with Parkinson's disease. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to images 3270 and 3271.

Two mouse fibroblasts, one of the most common types of cells in mammalian connective tissue. They play a key role in wound healing and tissue repair. This image was captured using structured illumination microscopy.

Two cells over a 2-hour period. The one on the bottom left goes through programmed cell death, also known as apoptosis. The one on the top right goes through cell division, also called mitosis. This video was captured using a confocal microscope.

Cells move forward with lamellipodia and filopodia supported by networks and bundles of actin filaments. Proper, controlled cell movement is a complex process. Recent research has shown that an actin-polymerizing factor called the Arp2/3 complex is the key component of the actin polymerization engine that drives amoeboid cell motility. ARPC3, a component of the Arp2/3 complex, plays a critical role in actin nucleation. In this photo, the ARPC3+/+ fibroblast cells were fixed and stained with Alexa 546 phalloidin for F-actin (red) and DAPI to visualize the nucleus (blue). ARPC3+/+ fibroblast cells with lamellipodia leading edge. Related to images 3328, 3329, 3330, 3331, and 3333.

A genetic disorder of the nervous system, neurofibromatosis causes tumors to form on nerves throughout the body, including a type of tumor called an optic nerve glioma that can result in childhood blindness. The image was used to demonstrate the unique imaging capabilities of one of our newest (at the time) laser scanning microscopes and is of a wildtype (normal) mouse retina in the optic fiber layer. This layer is responsible for relaying information from the retina to the brain and was fluorescently stained to reveal the distribution of glial cells (green), DNA and RNA in the cell bodies of the retinal ganglion neurons (orange) and their optic nerve fibers (red), and actin in endothelial cells surrounding a prominent branching blood vessel (blue). By studying the microscopic structure of normal and diseased retina and optic nerves, we hope to better understand the altered biology of the tissues in these tumors with the prospects of developing therapeutic interventions.

About half of all human proteins include chains of sugar molecules that are critical for the proteins to function properly. Appears in the NIGMS booklet Inside the Cell.

Each point in these colorful patchworks represents the correlation between two sleep-associated genes in fruit flies. Vibrant reds and oranges represent high and intermediate degrees of association between the genes, respectively. Genes in these areas show similar activity patterns in different fly lines. Cool blues represent gene pairs where one partner's activity is high and the other's is low. The green areas show pairs with activities that are not correlated. These quilt-like depictions help illustrate a recent finding that genes act in teams to influence sleep patterns.

Cell-like compartments that spontaneously emerged from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Image created using epifluorescence microscopy.

For more photos of cell-like compartments from frog eggs view: 6585, 6586, 6591, 6592, and 6593.

For videos of cell-like compartments from frog eggs view: 6587, 6588, 6589, and 6590.

Human embryonic stem cells differentiated into dopaminergic neurons, the type that degenerate in Parkinson's disease. Image courtesy of the California Institute for Regenerative Medicine. Related to images 3271 and 3285.

Stained kidney tissue. The kidney is an essential organ responsible for disposing wastes from the body and for maintaining healthy ion levels in the blood. It also secretes two hormones, erythropoietin (EPO) and calcitriol (a derivative of vitamin D), into the blood. It works like a purifier by pulling break-down products of metabolism, such as urea and ammonium, from the blood stream for excretion in urine. Related to image 3725.

This image shows the structure of a synapse, or junction between two nerve cells in three dimensions. From the brain of a mouse.

This image shows a cell in two stages of division: prometaphase (top) and metaphase (bottom). To form identical daughter cells, chromosome pairs (blue) separate via the attachment of microtubules made up of tubulin proteins (pink) to specialized structures on centromeres (green).

Influenza A infects a host cell when hemagglutinin grips onto glycans on its surface. Neuraminidase, an enzyme that chews sugars, helps newly made virus particles detach so they can infect other cells. Related to 213.

A light microscope image of a cell from the endosperm of an African globe lily (Scadoxus katherinae). This is one frame of a time-lapse sequence that shows cell division in action. The lily is considered a good organism for studying cell division because its chromosomes are much thicker and easier to see than human ones. Staining shows microtubules in red and chromosomes in blue. Here, condensed chromosomes are clearly visible and lined up.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, and 1019.

In 2006, scientists developed an optical microscopy technique enabling them to clearly see individual molecules within cells. In 2007, they took the technique, abbreviated STORM, a step further. They identified multicolored probes that let them peer into cells and clearly see multiple cellular components at the same time, such as these microtubules (green) and small hollows called clathrin-coated pits (red). Unlike conventional methods, the multicolor STORM technique produces a crisp and high resolution picture. A sharper view of how cellular components interact will likely help scientists answer some longstanding questions about cell biology.

A light microscope image of a cell from the endosperm of an African globe lily (Scadoxus katherinae). This is one frame of a time-lapse sequence that shows cell division in action. The lily is considered a good organism for studying cell division because its chromosomes are much thicker and easier to see than human ones. Staining shows microtubules in red and chromosomes in blue. Here, condensed chromosomes are clearly visible and are starting to separate to form two new cells.

For thousands of years, Chinese herbalists have treated malaria using Chang Shan, a root extract from a type of hydrangea that grows in Tibet and Nepal. Recent studies have suggested Chang Shan can also reduce scar formation, treat multiple sclerosis and even slow cancer progression.

Actin (purple), microtubules (yellow), and nuclei (green) are labeled in these cells by immunofluorescence. This image won first place in the Nikon 2003 Small World photo competition.

Dynein (green) is a motor protein that “walks” along microtubules (red, part of the cytoskeleton) and carries its cargo along with it. This video was captured through fluorescence microscopy.

Researchers used fluorescence in situ hybridization (FISH) to confirm the presence of long range DNA-DNA interactions in mouse embryonic stem cells. Here, two loci labeled in green (Oct4) and red that are 13 Mb apart on linear DNA are frequently found to be in close proximity. DNA-DNA colocalizations like this are thought to both reflect and contribute to cell type specific gene expression programs.

X-ray crystallography allows researchers to see structures too small to be seen by even the most powerful microscopes. To visualize the arrangement of atoms within molecules, researchers can use the diffraction patterns obtained by passing X-ray beams through crystals of the molecule. This is a common way for solving the structures of proteins. See image 2512 for a labeled version of this illustration. Featured in The Structures of Life.