An RNA molecule dynamically refolds itself as it is being synthesized. When the RNA is short, it ties itself into a “knot” (dark purple). For this domain to slip its knot, about 5 seconds into the video, another newly forming region (fuchsia) wiggles down to gain a “toehold.” About 9 seconds in, the temporarily knotted domain untangles and unwinds. Finally, at about 23 seconds, the strand starts to be reconfigured into the shape it needs to do its job in the cell.

An Arachnoidiscus diatom with a diameter of 190µm. Diatoms are microscopic algae that have cell walls made of silica, which is the strongest known biological material relative to its density. In Arachnoidiscus, the cell wall is a radially symmetric pillbox-like shell composed of overlapping halves that contain intricate and delicate patterns. Sometimes, Arachnoidiscus is called “a wheel of glass.”

This image was taken with the orientation-independent differential interference contrast microscope.

This image shows mouse fetal heart fibroblast cells. The muscle protein actin is stained red, and the cell nuclei are stained blue. The image was part of a study investigating stem cell-based approaches to repairing tissue damage after a heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine.

The illustration shows the capsid of human immunodeficiency virus (HIV) whose molecular features were resolved with cryo-electron microscopy (cryo-EM). On the left, the HIV capsid is "naked," a state in which it would be easily detected by and removed from cells. However, as shown on the right, when the viral capsid binds to and is covered with a host protein, called cyclophilin A (shown in red), it evades detection and enters and invades the human cell to use it to establish an infection. To learn more about how cyclophilin A helps HIV infect cells and how scientists used cryo-EM to find out the mechanism by which the HIV capsid attaches to cyclophilin A, see this news release by the University of Illinois. A study reporting these findings was published in the journal Nature Communications.

This image of a mammalian epithelial cell, captured in metaphase, was the winning image in the high- and super-resolution microscopy category of the 2012 GE Healthcare Life Sciences Cell Imaging Competition. The image shows microtubules (red), kinetochores (green) and DNA (blue). The DNA is fixed in the process of being moved along the microtubules that form the structure of the spindle.

The image was taken using the DeltaVision OMX imaging system, affectionately known as the "OMG" microscope, and was displayed on the NBC screen in New York's Times Square during the weekend of April 20-21, 2013. It was also part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

This animation shows atoms of the HIV capsid, the shell that encloses the virus's genetic material. Scientists determined the exact structure of the capsid using a variety of imaging techniques and analyses. They then entered this data into a supercomputer to produce this image. Related to image 3477.

A humorous treatment of the concept of a cycling cell.

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 2506 for an illustration without examples.

Three 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 closeup of roundworms here 6583.

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

Human metaphase chromosomes are visible with fluorescence in vitro hybridization (FISH). Centromeric alpha satellite DNA (green) are found in the heterochromatin at each centromere. Immunofluorescence with CENP-A (red) shows the centromere-specific histone H3 variant that specifies the kinetochore.

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

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.

This image shows the hierarchical ontology of genes, cellular components and processes derived from large genomic datasets. From Dutkowski et al. A gene ontology inferred from molecular networks Nat Biotechnol. 2013 Jan;31(1):38-45. Related to 3436.

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.

A cell in anaphase during mitosis: Chromosomes separate into two genetically identical groups and move to opposite ends of the spindle. 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.

In many animals, the egg cell develops alongside sister cells. These sister cells are called nurse cells in the fruit fly (Drosophila melanogaster), and their job is to “nurse” an immature egg cell, or oocyte. Toward the end of oocyte development, the nurse cells transfer all their contents into the oocyte in a process called nurse cell dumping. This video captures this transfer, showing significant shape changes on the part of the nurse cells (blue), which are powered by wavelike activity of the protein myosin (red). Researchers created the video using a confocal laser scanning microscope. Related to image 6753.

Groups of Staphylococcus aureus bacteria (blue) attached to a microstructured titanium surface (green) that mimics an orthopedic implant used in joint replacement. The attachment of pre-formed groups of bacteria may lead to infections because the groups can tolerate antibiotics and evade the immune system. This image was captured using a scanning electron microscope.

More information on the research that produced this image can be found in the Antibiotics paper "Free-floating aggregate and single-cell-initiated biofilms of Staphylococcus aureus" by Gupta et al.

Related to image 6804 and video 6805.

Related to image 6355.

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.

Related to images 1010, 1011, 1013, 1014, 1015, 1016, 1017, 1018, 1019, and 1021.

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.

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.

Cells keep time to know when to retire.

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.

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), mDia1 (green), and DAPI to visualize the nucleus (blue). mDia1 is localized at the lamellipodia of ARPC3+/+ fibroblast cells. Related to images 3328, 3329, 3331, 3332, and 3333.

A replica of a human retina grown from stem cells. It shows rod photoreceptors (nerve cells responsible for dark vision) in green and red/green cones (nerve cells responsible for red and green color vision) in red. The cell nuclei are stained blue. This image was captured using a confocal microscope.

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. 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. This image shows a pigment cell from zebrafish at high resolution. Related to images 5755, 5756, 5757 and 5758.

This illustration highlights spherical pre-synaptic vesicles that carry the neurotransmitter glutamate. The presynaptic and postsynaptic membranes are shown with proteins relevant for transmitting and modulating the neuronal signal.

PDB 101’s Opioids and Pain Signaling video explains how glutamatergic synapses are involved in the process of pain signaling.

The image visualizes a part of the yeast molecular interaction network. The lines in the network represent connections among genes (shown as little dots) and different-colored networks indicate subnetworks, for instance, those in specific locations or pathways in the cell. Researchers use gene or protein expression data to build these networks; the network shown here was visualized with a program called Cytoscape. By following changes in the architectures of these networks in response to altered environmental conditions, scientists can home in on those genes that become central "hubs" (highly connected genes), for example, when a cell encounters stress. They can then further investigate the precise role of these genes to uncover how a cell's molecular machinery deals with stress or other factors. Related to images 3732 and 3733.

Model of an enzyme, PanB, from Mycobacterium tuberculosis, the bacterium that causes most cases of tuberculosis. This enzyme is an attractive drug target.

Dose-response curves determine how much of a drug (X-axis) causes a particular effect, or a side effect, in the body (Y-axis). Featured in Medicines By Design.

A 3D model of the human endoplasmic reticulum membrane protein complex (EMC) that identifies its nine essential subunits. The EMC plays an important role in making membrane proteins, which are essential for all cellular processes. This is the first atomic-level depiction of the EMC. Its structure was obtained using single-particle cryo-electron microscopy.

This montage of tiny, transparent C. elegans--or roundworms--may offer insight into understanding human infertility. Researchers used fluorescent dyes to label the worm cells and watch the process of sex cell division, called meiosis, unfold as nuclei (blue) move through the tube-like gonads. Such visualization helps the scientists identify mechanisms that enable these roundworms to reproduce successfully. Because meiosis is similar in all sexually reproducing organisms, what the scientists learn could apply to humans.

Each morning, the nocturnal Hawaiian bobtail squid, Euprymna scolopes, hides from predators by digging into the sand. At dusk, it leaves the sand again to hunt.

Related to image 7010 and 7011.

An adult Hawaiian bobtail squid, Euprymna scolopes, (~4 cm) surrounded by newly hatched juveniles (~2 mm) in a bowl of seawater.

Related to image 7011 and video 7012.

Cell division is an incredibly coordinated process. It not only ensures that the new cells formed during this event have a full set of chromosomes, but also that they are endowed with all the cellular materials, including proteins, lipids and small functional compartments called organelles, that are required for normal cell activity. This proper apportioning of essential cell ingredients helps each cell get off to a running start.

This image shows an electron microscopy (EM) thin section taken at 10,000x magnification of a dividing yeast cell over-expressing the protein ubiquitin, which is involved in protein degradation and recycling. The picture features mother and daughter endosome accumulations (small organelles with internal vesicles), a darkly stained vacuole and a dividing nucleus in close contact with a cadre of lipid droplets (unstained spherical bodies).  Other dynamic events are also visible,  such as spindle microtubules in the nucleus and endocytic pits at the plasma membrane.

These extensive details were revealed thanks to a preservation method involving high-pressure freezing, freeze-substitution and Lowicryl HM20 embedding.

This image shows a normal fibroblast, a type of cell that is common in connective tissue and frequently studied in research labs. This cell has a healthy skeleton composed of actin (red) and microtubles (green). Actin fibers act like muscles to create tension and microtubules act like bones to withstand compression.

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

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool. The CRISPR system has two components joined together: a finely tuned targeting device (a small strand of RNA programmed to look for a specific DNA sequence) and a strong cutting device (an enzyme called Cas9 that can cut through a double strand of DNA). In this frame (2 of 4), the CRISPR machine locates the target DNA sequence once inserted into a cell.

For an explanation and overview of the CRISPR-Cas9 system, see the iBiology video, and find the full CRIPSR illustration here.

The incredible complexity of a mammalian eye (in this case from a mouse) is captured here. Each color represents a different type of cell. In total, there are nearly 70 different cell types, including the retina's many rings and the peach-colored muscle cells clustered on the left.

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

Top view of myelinated axons in a rat spinal root. Myelin is a type of fat that forms a sheath around and thus insulates the axon to protect it from losing the electrical current needed to transmit signals along the axon. The axoplasm inside the axon is shown in pink. Related to 3396.

A two-dimensional NMR spectrum of a protein, in this case a 2D 1H-15N HSQC NMR spectrum of a 228 amino acid DNA/RNA-binding protein.

These induced pluripotent stem cells (iPS cells) were derived from a woman's skin. Blue show nuclei. Green show a protein found in iPS cells but not in skin cells (NANOG). The red dots show the inactivated X chromosome in each cell. These cells can develop into a variety of cell types. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to image 3278.

The human body keeps time with a master clock called the suprachiasmatic nucleus or SCN. Situated inside the brain, it's a tiny sliver of tissue about the size of a grain of rice, located behind the eyes. It sits quite close to the optic nerve, which controls vision, and this means that the SCN "clock" can keep track of day and night. The SCN helps control sleep by coordinating the actions of billions of miniature "clocks" throughout the body. These aren't actually clocks, but rather are ensembles of genes inside clusters of cells that switch on and off in a regular, 24-hour cycle in our physiological day.

Floral pattern emerging as two bacterial species, motile Acinetobacter baylyi (red) and non-motile Escherichia coli (green), are grown together for 48 hours on 1% agar surface from a small inoculum in the center of a Petri dish.

See 6557 for a photo of this process at 24 hours on 0.75% agar surface.
See 6555 for another photo of this process at 48 hours on 1% agar surface.
See 6556 for a photo of this process at 72 hours on 0.5% agar surface.
See 6550 for a video of this process.

Proteins are 3D structures made up of smaller units. DNA is transcribed to RNA, which in turn is translated into amino acids. Amino acids form a protein strand, which has sections of corkscrew-like coils, called alpha helices, and other sections that fold flat, called beta sheets. The protein then goes through complex folding to produce the 3D structure.

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.

This lab space was designed for work on the induced pluripotent stem (iPS) cell collection, part of the NIGMS Human Genetic Cell Repository at the Coriell Institute for Medical Research.

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 3742.

Multiphoton fluorescence image of HeLa cells with cytoskeletal microtubules (magenta) and DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. See related images 3518, 3519, 3521, 3522.

Scientists revealed a detailed image of the genetic defect that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease. More information about the research behind this image can be found in a Biomedical Beat Blog posting from January 2014.