Mitochondria are the powerhouses of the cells, generating the energy the cells need to do their tasks and to stay alive. Researchers have studied mitochondria for some time because when these cell organelles don't work as well as they should, several diseases develop. In this photograph of cow cells taken with a microscope, the mitochondria were stained in bright yellow to visualize them in the cell. The large blue dots are the cell nuclei and the gray web is the cytoskeleton of the cells.

What looks a little like distant planets with some mysterious surface features are actually assemblies of proteins normally found in the cell's nucleolus, a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from differences in how the proteins in each compartment mix with water and with each other. These differences let the proteins readily separate from each other into the three nucleolus compartments.

This photo of nucleolus proteins in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows each of the nucleolus compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue). The researchers have found that these compartments spontaneously fuse with each other on encounter without mixing with the other compartments.

For more details on this research, see this press release from Princeton. Related to video 3789, video 3791 and image 3792.

The cryo-EM structure of human adenovirus D26 (HAdV-D26) at near atomic resolution (3.7 Å), determined in collaboration with the NRAMM facility*. In difference to archetype HAdV-C5, the HAdV-D26 is a low seroprevalent viral vector, which is being used to generate Ebola virus vaccines.

Opioid receptors on the surfaces of brain cells are involved in pleasure, pain, addiction, depression, psychosis, and other conditions. The receptors bind to both innate opioids and drugs ranging from hospital anesthetics to opium. Researchers at The Scripps Research Institute, supported by the NIGMS Protein Structure Initiative, determined the first three-dimensional structure of a human opioid receptor, a kappa-opioid receptor. In this illustration, the submicroscopic receptor structure is shown while bound to an agonist (or activator). The structure is superimposed on a poppy flower, the source of opium.

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.

Lysosomes have powerful enzymes and acids to digest and recycle cell materials.

A mouse brain that was genetically modified so that subpopulations of its neurons glow. Researchers often study mice because they share many genes with people and can shed light on biological processes, development, and diseases in humans.

This image was captured using a light sheet microscope.

Related to image 6929 and video 6931.

The extracellular matrix (ECM) is most prevalent in connective tissues but also is present between the stems (axons) of nerve cells, as shown here. Blue-colored nerve cell axons are surrounded by brown-colored, myelin-supplying Schwann cells, which act like insulation around an electrical wire to help speed the transmission of electric nerve impulses down the axon. The ECM is pale pink. The tiny brown spots within it are the collagen fibers that are part of the ECM.

If a picture is worth a thousand words, what's a movie worth? For researchers studying cell migration, a "documentary" of fruit fly cells (bright green) traversing an egg chamber could answer longstanding questions about cell movement. Historically, researchers have been unable to watch this cell migration unfold in living ovarian tissue in real time. But by developing a culture medium that allows fly eggs to survive outside their ovarian homes, scientists can observe the nuances of cell migration as it happens. Such details may shed light on how immune cells move to a wound and why cancer cells spread to other sites. See 3594 for still image.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3416, 3417, 3418, and 3419.

High-resolution time lapse of epithelial (skin) cell migration and wound healing. It shows an image taken every 13 seconds over the course of almost 14 minutes. The images were captured with quantitative orientation-independent differential interference contrast (DIC) microscope (left) and a conventional DIC microscope (right).

More information about the research that produced this video can be found in the Journal of Microscopy paper “An Orientation-Independent DIC Microscope Allows High Resolution Imaging of Epithelial Cell Migration and Wound Healing in a Cnidarian Model” by Malamy and Shribak.

Pigment cells are cells that give skin its color. In fishes and amphibians, like frogs and salamanders, pigment cells are responsible for the characteristic skin patterns that help these organisms to blend into their surroundings or attract mates. The pigment cells are derived from neural crest cells, which are cells originating from the neural tube in the early embryo. This image shows pigment cells called xanthophores in the skin of zebrafish; the cells glow (autofluoresce) brightly under light giving the fish skin a shiny, lively appearance. Investigating pigment cell formation and migration in animals helps answer important fundamental questions about the factors that control pigmentation in the skin of animals, including humans. Related to images 5754, 5756, 5757 and 5758.

These microscopic roundworms, called Caenorhabditis elegans, lack eyes and the opsin proteins used by visual systems to detect colors. However, researchers found that the worms can still sense the color of light in a way that enables them to avoid pigmented toxins made by bacteria. This image was captured using a stereo microscope.

Borrelia burgdorferi is a spirochete, a class of long, slender bacteria that typically take on a coiled shape. Infection with this bacterium causes Lyme disease.

Bacterial biofilms are tightly knit communities of bacterial cells growing on, for example, solid surfaces, such as in water pipes or on teeth. Here, cells of the bacterium Bacillus subtilis have formed a biofilm in a laboratory culture. Researchers have discovered that the bacterial cells in a biofilm communicate with each other through electrical signals via specialized potassium ion channels to share resources, such as nutrients, with each other. This insight may help scientists to improve sanitation systems to prevent biofilms, which often resist common treatments, from forming and to develop better medicines to combat bacterial infections. See the Biomedical Beat blog post Bacterial Biofilms: A Charged Environment for more information.

Featured in the March 15, 2012 issue of Biomedical Beat. Related to Hsp33 Figure 1, image 3354.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Using X-ray crystallography, researchers determined the structure of a CCD-1 molecule and a molecule of the antibiotic cefotaxime bound together. The structure revealed that CCD-1 provides extensive hydrogen bonding and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6767.

Vibrio fischeri cells (~ 2 mm), labeled with green fluorescent protein (GFP), passing through a very narrow bottleneck in the tissues (red) of the Hawaiian bobtail squid, Euprymna scolopes, on the way to the crypts where the symbiont population resides. This image was taken using a confocal fluorescence microscope.

Time lapse series shows short dynamin assemblies (not visible) constricting a lipid tube to make a "beads on a string" appearance, then cutting off one of the beads i.e., catalyzing membrane fission). The lipids are fluorescent (artificially colored). Ramachandran R, Pucadyil T.J., Liu Y.W., Acharya S., Leonard M., Lukiyanchuk V., Schmid S.L. 2009. Membrane insertion of the pleckstrin homology domain variable loop 1 is critical for dynamin-catalyzed vesicle scission. Mol Biol Cell. 2009 20:4630-9.

A cell in interphase, at the start of mitosis: Chromosomes duplicate, and the copies remain attached to each other. Mitosis is responsible for growth and development, as well as for replacing injured or worn out cells throughout the body. For simplicity, mitosis is illustrated here with only six chromosomes.

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.

A computer model of the cell membrane, where the plasma membrane is red, endoplasmic reticulum is yellow, and mitochondria are blue. This image relates to a July 27, 2009 article in Computing Life.

These ripples of color represent the outer membrane of the nucleus inside an astrocyte, a star-shaped cell inside the brain. Some proteins (green) act as keys to unlock other proteins (red) that form gates to let small molecules in and out of the nucleus (blue). Visualizing these different cell components at the boundary of the astrocyte nucleus enables researchers to study the molecular and physiological basis of neurological disorders, such as hydrocephalus, a condition in which too much fluid accumulates in the brain, and scar formation in brain tissue leading to abnormal neuronal activity affecting learning and memory. Scientists have now identified a pathway may be common to many of these brain diseases and begun to further examine it to find ways to treat certain brain diseases and injuries.

Collecting and transporting cellular waste and sorting it into recylable and nonrecylable pieces is a complex business in the cell. One key player in that process is the endosome, which helps collect, sort and transport worn-out or leftover proteins with the help of a protein assembly called the endosomal sorting complexes for transport (or ESCRT for short). These complexes help package proteins marked for breakdown into intralumenal vesicles, which, in turn, are enclosed in multivesicular bodies for transport to the places where the proteins are recycled or dumped. In this image, two multivesicular bodies (with yellow membranes) contain tiny intralumenal vesicles (with a diameter of only 25 nanometers; shown in red) adjacent to the cell's vacuole (in orange).

Scientists working with baker's yeast (Saccharomyces cerevisiae) study the budding inward of the limiting membrane (green lines on top of the yellow lines) into the intralumenal vesicles. This tomogram was shot with a Tecnai F-20 high-energy electron microscope, at 29,000x magnification, with a 0.7-nm pixel, ~4-nm resolution.

To learn more about endosomes, see the Biomedical Beat blog post The Cell’s Mailroom. Related to a microscopy photograph 5768 that was used to generate this illustration and a zoomed-out version 5769 of this illustration.

Yeast cells entering mitosis, also known as cell division. The green and magenta dots are two proteins that play important roles in mitosis. They show where the cells will split. This image was captured using wide-field microscopy with deconvolution.

Related to images 6792, 6793, 6794, 6797, 6798, and videos 6795 and 6796.

The G switch allows our bodies to respond rapidly to hormones. G proteins act like relay batons to pass messages from circulating hormones into cells. A hormone (red) encounters a receptor (blue) in the membrane of a cell. Next, a G protein (green) becomes activated and makes contact with the receptor to which the hormone is attached. Finally, the G protein passes the hormone's message to the cell by switching on a cell enzyme (purple) that triggers a response. See image 2536 and 2538 for other versions of this image. Featured in Medicines By Design.

This image shows neonatal mouse heart cells. These cells were grown in the lab on a chip that aligns the cells in a way that mimics what is normally seen in the body. Green shows the muscle protein toponin I. Red indicates the muscle protein actin, and blue indicates the cell nuclei. The work shown here was part of a study attempting to grow heart tissue in the lab to repair damage after a heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to images 3281 and 3282.

This image of the hippocampus was taken with an ultra-widefield high-speed multiphoton laser microscope. Tissue was stained to reveal the organization of glial cells (cyan), neurofilaments (green) and DNA (yellow). The microscope Deerinck used was developed in conjunction with Roger Tsien (2008 Nobel laureate in Chemistry) and remains a powerful and unique tool today.

The goal of the Protein Structure Initiative (PSI) is to determine the three-dimensional shapes of a wide range of proteins by solving the structures of representative members of each protein family found in nature. The collection of structures should serve as a valuable resource for biomedical research scientists.

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.

The arrangement of identical molecular components can make a dramatic difference. For example, carbon atoms can be arranged into dull graphite (left) or sparkly diamonds (right). See image 2507 for an illustration with examples.

Many of today's medicines come from products found in nature, such as this sponge found off the coast of Palau in the Pacific Ocean. Chemists have synthesized a compound called Palau'amine, which appears to act against cancer, bacteria and fungi. In doing so, they invented a new chemical technique that will empower the synthesis of other challenging molecules.

Like a map showing heavily traveled roads, this mathematical model of metabolic activity inside an E. coli cell shows the busiest pathway in white. Reaction pathways used less frequently by the cell are marked in red (moderate activity) and green (even less activity). Visualizations like this one may help scientists identify drug targets that block key metabolic pathways in bacteria.

Model of a major secreted protein of unknown function, which is only found in mycobacteria, the class of bacteria that causes tuberculosis. Based on structural similarity, this protein may be involved in host-bacterial interactions.

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.

Cell showing overproduction of the ARTS protein (red). ARTS triggers apoptosis, as shown by the activation of caspase-3 (green) a key tool in the cell's destruction. The nucleus is shown in blue. Image is featured in October 2015 Biomedical Beat blog post Cool Images: A Halloween-Inspired Cell Collection.

Model of the catalytic portion of an enzyme, receptor-type tyrosine-protein phosphatase from humans. The enzyme consists of two identical protein subunits, shown in blue and green. The groups made up of purple and red balls represent phosphate groups, chemical groups that can influence enzyme activity. This phosphatase removes phosphate groups from the enzyme tyrosine kinase, counteracting its effects.

Serum albumin (SA) is the most abundant protein in the blood plasma of mammals. SA has a characteristic heart-shape structure and is a highly versatile protein. It helps maintain normal water levels in our tissues and carries almost half of all calcium ions in human blood. SA also transports some hormones, nutrients and metals throughout the bloodstream. Despite being very similar to our own SA, those from other animals can cause some mild allergies in people. Therefore, some scientists study SAs from humans and other mammals to learn more about what subtle structural or other differences cause immune responses in the body.

Related to entries 3745 and 3746.

These six-month-old axolotls, a kind of salamander, glow green and blue under ultraviolet light. That's because they were genetically modified to make harmless green fluorescent protein, or GFP. Like X-ray vision, GFP lets you see inside the axolotls as they hang out in their aquarium. GFP not only can reveal internal structures in living organisms, but it also can light up specific cells and even proteins within a cell. That allows scientists to identify and track things like cancer cells.

NIGMS-funded researchers led by Roger Kornberg solved the structure of RNA polymerase II. This is the enzyme in mammalian cells that catalyzes the transcription of DNA into messenger RNA, the molecule that in turn dictates the order of amino acids in proteins. For his work on the mechanisms of mammalian transcription, Kornberg received the Nobel Prize in Chemistry in 2006.

A sensor particle being engulfed by a macrophage—an immune cell—and encapsuled in a compartment called a phagosome. The phagosome then fuses with lysosomes—another type of compartment. The left video shows snowman-shaped sensor particles with fluorescent green nanoparticle “heads” and “bodies” colored red by Förster Resonance Energy Transfer (FRET)-donor fluorophores. The middle video visualizes light blue FRET signals that are only generated when the “snowman” sensor—the FRET-donor—fuses with the lysosomes, which are loaded with FRET-acceptors. The right video combines the other two. The videos were captured using epi-fluorescence microscopy.

More details can be found in the paper “Transport motility of phagosomes on actin and microtubules regulates timing and kinetics of their maturation” by Yu et al.

Image of Streptococcus, a type (genus) of spherical bacteria that can colonize the throat and back of the mouth. Stroptococci often occur in pairs or in chains, as shown here.

C. elegans, a tiny roundworm, with a ribosomal protein glowing red and muscle fibers glowing green. Researchers used these worms to study a molecular pathway that affects aging. The ribosomal protein is involved in protein translation and may play a role in dietary restriction-induced longevity. Image created using confocal microscopy.
View group of roundworms here 6582.
View closeup of roundworms here 6583.

Cross section of human skeletal muscle. Image taken with a confocal fluorescent light microscope.

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.

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, 1049, 1050, 1051 and 1052.

Stained glomeruli in the kidney. The kidney is an essential organ responsible for disposing wastes from the body and for maintaining healthy ion levels in the blood. It works like a purifier by pulling break-down products of metabolism, such as urea and ammonium, from the bloodstream for excretion in urine. The glomerulus is a structure that helps filter the waste compounds from the blood. It consists of a network of capillaries enclosed within a Bowman's capsule of a nephron, which is the structure in which ions exit or re-enter the blood in the kidney.

Actin is an essential protein in a cell's skeleton (cytoskeleton). It forms a dense network of thin filaments in the cell. Here, researchers have used a technique called stochastic optical reconstruction microscopy (STORM) to visualize the actin network in a cell in three dimensions. The actin strands were labeled with a dye called Alexa Fluor 647-phalloidin.  This image appears in a study published by Nature Methods, which reports how researchers use STORM to visualize the cytoskeleton.

The nucleolus is a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from differences in how the proteins in each compartment mix with water and with each other. These differences let the proteins readily separate from each other into the three nucleolus compartments.

This video of nucleoli in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows how each of the compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue) spontaneously fuse with each other on encounter without mixing with the other compartments.

For more details on this research, see this press release from Princeton. Related to video 3789, image 3792 and image 3793.

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 2571 and 2572.