A light organ (~0.5 mm across) of a juvenile Hawaiian bobtail squid, Euprymna scolopes. Movement of cilia on the surface of the organ aggregates bacterial symbionts (green) into two areas above sets of pores that lead to interior crypts. This image was taken using a confocal fluorescence microscope.

Related to images 7016, 7017, 7019, and 7020.

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

Neurons (green) and glial cells from isolated dorsal root ganglia express COX-2 (red) after exposure to an inflammatory stimulus (cell nuclei are blue). Lawrence Marnett and colleagues have demonstrated that certain drugs selectively block COX-2 metabolism of endocannabinoids -- naturally occurring analgesic molecules -- in stimulated dorsal root ganglia. Featured in the October 20, 2011 issue of Biomedical Beat.

Sulfite oxidase is an enzyme that is essential for normal neurological development in children. This video shows the active site of the enzyme and its molybdenum cofactor visible as a faint ball-and-stick representation buried within the protein. The positively charged channel (blue) at the active site contains a chloride ion (green) and three water molecules (red). As the protein oscillates, one can see directly down the positively charged channel. At the bottom is the molybdenum atom of the active site (light blue) and its oxo group (red) that is transferred to sulfite to form sulfate in the catalytic reaction.

The parasitic worm that causes schistosomiasis hatches in water and grows up in a freshwater snail, as shown here. Once mature, the worm swims back into the water, where it can infect people through skin contact. Initially, an infected person might have a rash, itchy skin, or flu-like symptoms, but the real damage is done over time to internal organs.

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

Cell-like compartments spontaneously emerge from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Regions without nuclei formed smaller compartments. Video created using epifluorescence microscopy.

For more photos of cell-like compartments from frog eggs view: 6584, 6585, 6586, 6591, 6592, and 6593.

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

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Stained cell membranes (green) and cell walls (red) reveal the connections between cells. Younger cells take up more cell membrane stain, while older cells take up more cell wall stain, leading to the color differences seen here. This image was captured using spinning disk confocal microscopy.

Related to images 6970 and 6971.

Macrophages (green) are the professional eaters of our immune system. They are constantly surveilling our tissues for targets—such as bacteria, dead cells, or even cancer—and clearing them before they can cause harm. In this image, researchers were testing how macrophages responded to different molecules that were attached to silica beads (magenta) coated with a lipid bilayer to mimic a cell membrane.

Find more information on this image in the NIH Director’s Blog post "How to Feed a Macrophage."

The receptor is shown bound to a partial inverse agonist, carazolol.

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.

Damage to each person's genome, often called the "Book of Life," accumulates with time. Such DNA mutations arise from errors in the DNA copying process, as well as from external sources, such as sunlight and cigarette smoke. DNA mutations are known to cause cancer and also may contribute to cellular aging.

A study published in March 2012 used cryo-electron microscopy to determine the structure of the DNA replication origin recognition complex (ORC), a semi-circular, protein complex (yellow) that recognizes and binds DNA to start the replication process. The ORC appears to wrap around and bend approximately 70 base pairs of double stranded DNA (red and blue). Also shown is the protein Cdc6 (green), which is also involved in the initiation of DNA replication. The video shows the structure from different angles. See related image 3597.

Vibrio fischeri (2 mm in length) is the exclusive symbiotic partner of the Hawaiian bobtail squid, Euprymna scolopes. After this bacterium uses its flagella to swim from the seawater into the light organ of a newly hatched juvenile, it colonizes the host and loses the appendages. This image was taken using a scanning electron microscope.

T cells are white blood cells that are important in defending the body against bacteria, viruses and other pathogens. Each T cell carries proteins, called T-cell receptors, on its surface that are activated when they come in contact with an invader. This activation sets in motion a cascade of biochemical changes inside the T cell to mount a defense against the invasion. Scientists have been interested for some time what happens after a T-cell receptor is activated. One obstacle has been to study how this signaling cascade, or pathway, proceeds inside T cells.

In this image, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The image shows two key steps during the signaling process: clustering of a protein called linker for activation of T cells (LAT) (blue) and polymerization of the cytoskeleton protein actin (red). The findings show that the T-cell receptor signaling proteins self-organize into separate physical and biochemical compartments. This new system of studying molecular pathways outside the cells will enable scientists to better understand how the immune system combats microbes or other agents that cause infection.

To learn more how researchers assembled this T-cell receptor pathway, see this press release from HHMI's Marine Biological Laboratory Whitman Center. Related to video 3786.

On the left, a cross-section slice of a rat pancreas cell captured using cryo-electron tomography (cryo-ET). On the right, a 3D, color-coded version of the image highlighting cell structures. Visible features include microtubules (neon-green rods), ribosomes (small yellow circles), and vesicles (dark-blue circles). These features are surrounded by the partially visible endoplasmic reticulum (light blue). The black line at the bottom right of the left image represents 200 nm. Related to image 6607.

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.

Crystals of fungal lipase protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool.

Frame 1 shows the two components of the CRISPR system: a strong cutting device (an enzyme called Cas9 that can cut through a double strand of DNA), and a finely tuned targeting device (a small strand of RNA programmed to look for a specific DNA sequence).

In frame 2, the CRISPR machine locates the target DNA sequence once inserted into a cell.

In frame 3, the Cas9 enzyme cuts both strands of the DNA.

Frame 4 shows a repaired DNA strand with new genetic material that researchers can introduce, which the cell automatically incorporates into the gap when it repairs the broken DNA.

For an explanation and overview of the CRISPR-Cas9 system, see the iBiology video.

Download the individual frames: Frame 1, Frame 2, Frame 3, and Frame 4.

A crane fly spermatocyte during metaphase of meiosis-I, a step in the production of sperm. A meiotic spindle pulls apart three pairs of autosomal chromosomes, along with a sex chromosome on the right. Tubular mitochondria surround the spindle and chromosomes. This video was captured with quantitative orientation-independent differential interference contrast and is a time lapse showing a 1-second image taken every 30 seconds over the course of 30 minutes.

More information about the research that produced this video can be found in the J. Biomed Opt. paper “Orientation-Independent Differential Interference Contrast (DIC) Microscopy and Its Combination with Orientation-Independent Polarization System” by Shribak et. al.

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.

This ACAPELLA robot for capillary protein crystallization grows protein crystals, freezes them, and centers them without manual intervention. The close-up is a view of one of the dispensers used for dispensing proteins and reagents.

This is a magnified view of an Arabidopsis thaliana leaf a few days after being exposed to the pathogen Hyaloperonospora arabidopsidis. The plant from which this leaf was taken is genetically resistant to the pathogen. The spots in blue show areas of localized cell death where infection occurred, but it did not spread. Compare this response to that shown in Image 2782. Jeff Dangl has been funded by NIGMS to study the interactions between pathogens and hosts that allow or suppress infection.

The lubber grasshopper, found throughout the southern United States, is frequently used in biology classes to teach students about the respiratory system of insects. Unlike mammals, which have red blood cells that carry oxygen throughout the body, insects have breathing tubes that carry air through their exoskeleton directly to where it's needed. This image shows the breathing tubes embedded in the weblike sheath cells that cover developing egg chambers.

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 structure of a DNA repair enzyme superfamily representative from the human gastrointestinal bacterium Enterococcus faecalis. European scientists used this structure to generate homologous structures. Featured as the May 2007 Protein Structure Initiative Structure of the Month.

A robot is transferring 96 purification columns to a vacuum manifold for subsequent purification procedures.

Like a group of barnacles hanging onto a rock, these human cells hang onto a matrix coated glass slide. Actin stress fibers, stained magenta, and the protein vinculin, stained green, make this adhesion possible. The fibroblast nuclei are stained blue.

Fruit flies are a common model organism for basic medical research.

An anchor cell (red) pushes through the basement membrane (green) that surrounds it. Some cells are able to push through the tough basement barrier to carry out important tasks--and so can cancer cells, when they spread from one part of the body to another. No one has been able to recreate basement membranes in the lab and they're hard to study in humans, so Duke University researchers turned to the simple worm C. elegans. The researchers identified two molecules that help certain cells orient themselves toward and then punch through the worm's basement membrane. Studying these molecules and the genes that control them could deepen our understanding of cancer spread.

Neutrophil-like cells (blue) in a microfluidic chip preferentially migrating toward LTB4 over fMLP. A neutrophil is a type of white blood cell that is part of the immune system and helps the body fight infection. Both LTB4 and fMLP are molecules involved in immune response. Microfluidic chips are small devices containing microscopic channels, and they are used in a range of applications, from basic research on cells to pathogen detection. The scale bar in this video is 500μm.

A fruit fly ovary, shown here, contains as many as 20 eggs. Fruit flies are not merely tiny insects that buzz around overripe fruit--they are a venerable scientific tool. Research on the flies has shed light on many aspects of human biology, including biological rhythms, learning, memory and neurodegenerative diseases. Another reason fruit flies are so useful in a lab (and so successful in fruit bowls) is that they reproduce rapidly. About three generations can be studied in a single month. Related to image 3607.

Cultured hippocampal neurons grown on a substrate of glial cells (astrocytes). The glial cells form the pink/brown underlayment in this image. The tan threads are the neurons. The round tan balls are synapses, the points where neurons meet and communicate with each other. The cover slip underlying the cells is green. Neurons in culture can be used to study synaptic plasticity, activity-dependent protein turnover, and other topics in neuroscience.

This normal human skin cell was treated with a growth factor that triggered the formation of specialized protein structures that enable the cell to move. We depend on cell movement for such basic functions as wound healing and launching an immune response.

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

Disassembly of vasculature in kdr:GFP frogs following addition of 250 µM TBZ. Related to images 3404 and 3505.

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 image is a partial model of a doublet microtubule’s structure based on cryo-electron microscopy images. Video can be found here 6549.

Shortly after a pregnant woman gives birth, her breasts start to secrete milk. This process is triggered by hormonal and genetic cues, including the protein Elf5. Scientists discovered that Elf5 also has another job--it staves off cancer. Early in the development of breast cancer, human breast cells often lose Elf5 proteins. Cells without Elf5 change shape and spread readily--properties associated with metastasis. This image shows cells in the mouse mammary gland that are lacking Elf5, leading to the overproduction of other proteins (red) that increase the likelihood of metastasis.

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.

These images show frog cells in interphase. The cells are Xenopus XL177 cells, which are derived from tadpole epithelial cells. The microtubules are green and the chromosomes are blue. Related to 3442.

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.

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 eerily glowing blob isn't an alien or a creature from the deep sea--it's a mouse embryo just eight and a half days old. The green shell and core show a protein called Smad4. In the center, Smad4 is telling certain cells to begin forming the mouse's liver and pancreas. Researchers identified a trio of signaling pathways that help switch on Smad4-making genes, starting immature cells on the path to becoming organs. The research could help biologists learn how to grow human liver and pancreas tissue for research, drug testing and regenerative medicine. In addition to NIGMS, NIH's National Institute of Diabetes and Digestive and Kidney Diseases also supported this work.

Misfolded proteins (green) within mitochondria (red). Related to video 5877.

This image of laboratory-grown cells was taken with the help of a scanning electron microscope, which yields detailed images of cell surfaces.

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 1051.

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 global "map of the protein structure universe." The Berkeley Structural Genomics Center has developed a method to visualize the vast universe of protein structures in which proteins of similar structure are located close together and those of different structures far away in the space. This map, constructed using about 500 of the most common protein folds, reveals a highly non-uniform distribution, and shows segregation between four elongated regions corresponding to four different protein classes (shown in four different colors). Such a representation reveals a high-level of organization of the protein structure universe.

The TRPA1 protein is responsible for the burn you feel when you taste a bite of sushi topped with wasabi. Known therefore informally as the "wasabi receptor," this protein forms pores in the membranes of nerve cells that sense tastes or odors. Pungent chemicals like wasabi or mustard oil cause the pores to open, which then triggers a tingling or burn on our tongue. This receptor also produces feelings of pain in response to chemicals produced within our own bodies when our tissues are damaged or inflamed. Researchers used cryo-EM to reveal the structure of the wasabi receptor at a resolution of about 4 angstroms (a credit card is about 8 million angstroms thick). This detailed structure can help scientists understand both how we feel pain and how we can limit it by developing therapies to block the receptor. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail.

Histone proteins loop together with double-stranded DNA to form a structure that resembles beads on a string. See image 2561 for a labeled version of this illustration. Featured in The New Genetics.

Crystal structure of oligoendopeptidase F, a protein slicing enzyme from Bacillus stearothermophilus, a bacterium that can cause food products to spoil. The crystal was formed using a microfluidic capillary, a device that enables scientists to independently control the parameters for protein crystal nucleation and growth. Featured as one of the July 2007 Protein Structure Initiative Structures of the Month.

The chemical structure of the morphine molecule

A zebrafish embryo. The blue areas are cell bodies, the green lines are blood vessels, and the red glow is blood. This image was created by stitching together five individual images captured with a hyperspectral multipoint confocal fluorescence microscope that was developed at the Eliceiri Lab.