A macrophage—a type of immune cell that engulfs invaders—“eats” and is activated by a “two-faced” Janus particle. The particle is called “two-faced” because each of its two hemispheres is coated with a different type of molecule, shown here in red and cyan. During macrophage activation, a transcription factor tagged with a green fluorescence protein (NF-κB) gradually moves from the cell’s cytoplasm into its nucleus and causes DNA transcription. The distribution of molecules on “two-faced” Janus particles can be altered to control the activation of immune cells. Details on this “geometric manipulation” strategy can be found in the Proceedings of the National Academy of Sciences paper "Geometrical reorganization of Dectin-1 and TLR2 on single phagosomes alters their synergistic immune signaling" by Li et al. and the Scientific Reports paper "Spatial organization of FcγR and TLR2/1 on phagosome membranes differentially regulates their synergistic and inhibitory receptor crosstalk" by Li et al. This video was captured using epi-fluorescence microscopy.

Related to video 6800.

NIGMS staff are located in the Natcher Building on the NIH campus.

This video results from a research project to visualize which regions of the adult fruit fly (Drosophila) brain derive from each neural stem cell. First, researchers collected several thousand fruit fly larvae and fluorescently stained a random stem cell in the brain of each. The idea was to create a population of larvae in which each of the 100 or so neural stem cells was labeled at least once. When the larvae grew to adults, the researchers examined the flies’ brains using confocal microscopy. With this technique, the part of a fly’s brain that derived from a single, labeled stem cell “lights up.” The scientists photographed each brain and digitally colorized its lit-up area. By combining thousands of such photos, they created a three-dimensional, color-coded map that shows which part of the Drosophila brain comes from each of its ~100 neural stem cells. In other words, each colored region shows which neurons are the progeny or “clones” of a single stem cell. This work established a hierarchical structure as well as nomenclature for the neurons in the Drosophila brain. Further research will relate functions to structures of the brain.

Related to images 5838 and 5868.

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.

Related to images 1010, 1011, 1012, 1013, 1014, 1016, 1017, 1018, 1019, and 1021.

Early on, this Arabidopsis plant embryo picks sides: While one end will form the shoot, the other will take root underground. Short pieces of RNA in the bottom half (blue) make sure that shoot-forming genes are expressed only in the embryo's top half (green), eventually allowing a seedling to emerge with stems and leaves. Like animals, plants follow a carefully orchestrated polarization plan and errors can lead to major developmental defects, such as shoots above and below ground. Because the complex gene networks that coordinate this development in plants and animals share important similarities, studying polarity in Arabidopsis--a model organism--could also help us better understand human development.

This fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.

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.

Closeup of C. elegans, tiny roundworms, 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 single roundworm here 6581.
View group of roundworms here 6582.

Electron density maps such as this one are generated from the diffraction patterns of X-rays passing through protein crystals. These maps are then used to generate a model of the protein's structure by fitting the protein's amino acid sequence (yellow) into the observed electron density (blue).

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 global "map of the protein structure universe" indicating the positions of specific proteins. The preponderance of small, less-structured proteins near the origin, with the more highly structured, large proteins towards the ends of the axes, may suggest the evolution of protein structures.

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.

Disassembly of vasculature and reassembly after addition and then washout of 250 µM TBZ in kdr:GFP frogs. Related to images 3403 and 3404.

What looks like the gossamer wings of a butterfly is actually the retina of a mouse, delicately snipped to lay flat and sparkling with fluorescent molecules. The image is from a research project investigating the promise of gene therapy for glaucoma. It was created at an NIGMS-funded advanced microscopy facility that develops technology for imaging across many scales, from whole organisms to cells to individual molecules.

The ability to obtain high-resolution imaging of tissue as large as whole mouse retinas was made possible by a technique called large-scale mosaic confocal microscopy, which was pioneered by the NIGMS-funded National Center for Microscopy and Imaging Research. The technique is similar to Google Earth in that it computationally stitches together many small, high-resolution images.

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 6930 and video 6931.

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.

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.

This 1 1/2-minute video animation was produced for chemical biologist Stuart Schreiber's lab page. The animation shows how diverse chemical structures can be produced in the lab.

The body uses a variety of ion channels to transport small molecules across cell membranes.

In the worm C. elegans, double-stranded RNA made in neurons can silence matching genes in a variety of cell types through the transport of RNA between cells. The head region of three worms that were genetically modified to express a fluorescent protein were imaged and the images were color-coded based on depth. The worm on the left lacks neuronal double-stranded RNA and thus every cell is fluorescent. In the middle worm, the expression of the fluorescent protein is silenced by neuronal double-stranded RNA and thus most cells are not fluorescent. The worm on the right lacks an enzyme that amplifies RNA for silencing. Surprisingly, the identities of the cells that depend on this enzyme for gene silencing are unpredictable. As a result, worms of identical genotype are nevertheless random mosaics for how the function of gene silencing is carried out. For more, see journal article and press release. Related to image 6532.

Developing fruit fly spermatids require caspase activity (green) for the elimination of unwanted organelles and cytoplasm via apoptosis.

A light microscope image of cells 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, two cells have formed after a round of mitosis.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, and 1021.

A mouse's fat cells (red) are shown surrounded by a network of blood vessels (green). Fat cells store and release energy, protect organs and nerve tissues, insulate us from the cold, and help us absorb important vitamins.

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

This network map shows the overlap (green) between the long QT syndrome (yellow) and epilepsy (blue) protein-interaction neighborhoods located within the human interactome. Researchers have learned to integrate genetic, cellular and clinical information to find out why certain medicines can trigger fatal heart arrhythmias. Featured in Computing Life magazine.

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.

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.

Three fruit fly (Drosophila melanogaster) ovarioles (yellow, blue, and magenta) with egg cells visible inside them. Ovarioles are tubes in the reproductive systems of female insects. Egg cells form at one end of an ovariole and complete their development as they reach the other end, as shown in the yellow wild-type ovariole. This process requires an important protein that is missing in the blue and magenta ovarioles. This image was created using confocal microscopy.

More information on the research that produced this image can be found in the Current Biology paper “Gatekeeper function for Short stop at the ring canals of the Drosophila ovary” by Lu et al.

Using techniques that took 4 years to design, a team of developmental biologists showed that certain proteins can direct the subdivision of fruit fly and chicken nervous system tissue into the regions depicted here in blue, green, and red. Molecules called bone morphogenetic proteins (BMPs) helped form this fruit fly embryo. While scientists knew that BMPs play a major role earlier in embryonic development, they didn't know how the proteins help organize nervous tissue. The findings suggest that BMPs are part of an evolutionarily conserved mechanism for organizing the nervous system. The National Institute of Neurological Disorders and Stroke also supported this work.

Glide across an icy canyon, where you see smiling snowmen and waddling penguins. Toss a snowball, hear it smash against an igloo, and then watch it explode in bright colors. Psychologists David Patterson and Hunter Hoffman of the University of Washington in Seattle developed this virtual "Snow World" to test whether immersing someone in a pretend reality could ease pain during burn treatment and other medical procedures. They found that people fully engaged in the virtual reality experience reported 60 percent less pain. The technology offers a promising way to manage pain.

RNA polymerase (purple) is a complex enzyme at the heart of transcription. During this process, the enzyme unwinds the DNA double helix and uses one strand (darker orange) as a template to create the single-stranded messenger RNA (green), later used by ribosomes for protein synthesis.

From the RNA polymerase II elongation complex of Saccharomyces cerevisiae (PDB entry 1I6H) as seen in PDB-101's What is a Protein? video.

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.

This image shows an osteosarcoma cell with DNA in blue, energy factories (mitochondria) in yellow, and actin filaments—part of the cellular skeleton—in purple. One of the few cancers that originate in the bones, osteosarcoma is rare, with about a thousand new cases diagnosed each year in the United States.

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

Along with blood vessels (red) and nerve cells (green), this mouse brain shows abnormal protein clumps known as plaques (blue). These plaques multiply in the brains of people with Alzheimer's disease and are associated with the memory impairment characteristic of the disease. Because mice have genomes nearly identical to our own, they are used to study both the genetic and environmental factors that trigger Alzheimer's disease. Experimental treatments are also tested in mice to identify the best potential therapies for human patients.

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

Drosophila adult brain showing that an adipokine (fat hormone) generates a response from neurons (aqua) and regulates insulin-producing neurons (red).

Related to images 6982, 6983, and 6984.

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).

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3415, 3416, 3417, 3418, and 3419.

Enzymes speed up chemical reactions by reducing the amount of energy needed for the reactions. The substrate (lactose) binds to the active site of the enzyme (lactase) and is converted into products (sugars).

A color-coded, 3D model of a rat pancreatic β cell. This type of cell produces insulin, a hormone that helps regulate blood sugar. Visible are mitochondria (pink), insulin vesicles (yellow), the nucleus (dark blue), and the plasma membrane (teal). This model was created based on soft X-ray tomography (SXT) images.

Los ritmos circadianos son cambios físicos, mentales y conductuales que siguen un ciclo de 24 horas. Los ritmos circadianos típicos conducen a un nivel alto de energía durante la mitad del día (de 10 a.m. a 1 p.m.) y un bajón por la tarde. De noche, los ritmos circadianos hacen que la hormona melatonina aumente, lo que hace que la persona se sienta somnolienta.

Vea 6611 para la versión en inglés de esta infografía.

Automated methods using micromachined silicon are used at the Northeast Collaboratory for Structural Genomics to mount protein crystals for X-ray crystallography.

Model of the enzyme aminopeptidase N from the human pathogen Neisseria meningitidis, which can cause meningitis epidemics. The structure provides insight on the active site of this important molecule.

Cancer cells can change their migration phenotype, which includes their shape and the way that they move to invade different tissues. This movie shows breast cancer cells forming a tumor spheroid—a 3D ball of cancer cells—and invading the surrounding tissue. Images were taken using a laser scanning confocal microscope, and artificial intelligence (AI) models were used to segment and classify the images by migration phenotype. On the right side of the video, each phenotype is represented by a different color, as recognized by the AI program based on identifiable characteristics of those phenotypes. The movie demonstrates how cancer cells can use different migration modes during growth and metastasis—the spreading of cancer cells within the body.

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.

The head of an axolotl—a type of salamander—that has been genetically modified so that its developing nervous system glows purple and its Schwann cell nuclei appear light blue. Schwann cells insulate and provide nutrients to peripheral nerve cells. Researchers often study axolotls for their extensive regenerative abilities. They can regrow tails, limbs, spinal cords, brains, and more. The researcher who took this image focuses on the role of the peripheral nervous system during limb regeneration.

This image was captured using a light sheet microscope.

Related to images 6928 and 6932.

A biofilm is a highly organized community of microorganisms that develops naturally on certain surfaces. These communities are common in natural environments and generally do not pose any danger to humans. Many microbes in biofilms have a positive impact on the planet and our societies. Biofilms can be helpful in treatment of wastewater, for example. This dime-sized biofilm, however, was formed by the opportunistic pathogen Pseudomonas aeruginosa. Under some conditions, this bacterium can infect wounds that are caused by severe burns. The bacterial cells release a variety of materials to form an extracellular matrix, which is stained red in this photograph. The matrix holds the biofilm together and protects the bacteria from antibiotics and the immune system.

The long, stringy DNA that makes up genes is spooled within chromosomes inside the nucleus of a cell. (Note that a gene would actually be a much longer stretch of DNA than what is shown here.) See image 2540 for a labeled version of this illustration. Featured in The New Genetics.

Multiphoton fluorescence image of HeLa cells stained with the actin binding toxin phalloidin (red), microtubules (cyan) and cell nuclei (blue). Nikon RTS2000MP custom laser scanning microscope. See related images 3518, 3519, 3520, 3522.

Learn how research organisms, such as fruit flies and mice, can help us understand and treat human diseases. Discover more resources from NIGMS’ Pathways collaboration with Scholastic. View the video on YouTube for closed captioning.

To better understand cell movements in developing embryos, researchers isolated cells from early zebrafish embryos and grew them as clusters. Provided with the right signals, the clusters replicated some cell movements seen in intact embryos. Each line in this image depicts the movement of a single cell. The image was created using time-lapse confocal microscopy. Related to video 6776.

Real-time movie of young squids. Squids are often used as research organisms due to having the largest nervous system of any invertebrate, complex behaviors like instantaneous camouflage, and other unique traits.

This video was taken with polychromatic polarization microscope, as described in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak. The color is generated by interaction of white polarized light with the squid’s transparent soft tissue. The tissue works as a living tunable spectral filter, and the transmission band depends on the molecular orientation. When the young squid is moving, the tissue orientation changes, and its color shifts accordingly.