An adult Hawaiian bobtail squid, Euprymna scolopes, swimming next to a submerged hand.

Related to image 7010 and video 7012.

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

Cytoplasmic linker protein (CLIP)-170 is a microtubule plus-end-tracking protein that regulates microtubule dynamics and links microtubule ends to different intracellular structures. In this movie, the gene for CLIP-170 has been fused with green fluorescent protein (GFP). When the protein is expressed in cells, the activities can be monitored in real time. Here, you can see CLIP-170 streaming towards the edges of the cell.

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.

The signal is obtained by allowing proteins in human serum to interact with glycan (polysaccharide) arrays. The arrays are shown in replicate so the pattern is clear. Each spot contains a specific type of glycan. Proteins have bound to the spots highlighted in green.

This image shows collagen, a fibrous protein that's the main component of the extracellular matrix (ECM). Collagen is a strong, ropelike molecule that forms stretch-resistant fibers. The most abundant protein in our bodies, collagen accounts for about a quarter of our total protein mass. Among its many functions is giving strength to our tendons, ligaments and bones and providing scaffolding for skin wounds to heal. There are about 20 different types of collagen in our bodies, each adapted to the needs of specific tissues.

In the top snapshots, the brain of a sleep-deprived fruit fly glows orange, marking high concentrations of a synaptic protein called Bruchpilot (BRP) involved in communication between neurons. The color particularly lights up brain areas associated with learning. By contrast, the bottom images from a well-rested fly show lower levels of the protein. These pictures illustrate the results of an April 2009 study showing that sleep reduces the protein's levels, suggesting that such "downscaling" resets the brain to normal levels of synaptic activity and makes it ready to learn after a restful night.

In the determination of protein structures by X-ray crystallography, this unique soft (l = 2.29Å) X-ray source is used to collect anomalous scattering data from protein crystals containing light atoms such as sulfur, calcium, zinc and phosphorous. These data can be used to image the protein.

Like a major city, a cell teems with specialized workers that carry out its daily operations--making energy, moving proteins, or helping with other tasks. Researchers took microscopic pictures of thin layers of a cell and then combined them to make this 3-D image featuring color-coded organelles--the cell's "workers." Using this image, scientists can understand how these specialized components fit together in the cell's packed inner world.

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.

The proteasome is a critical multiprotein complex in the cell that breaks down and recycles proteins that have become damaged or are no longer needed. This illustration shows a protein substrate (red) that is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region gets engaged by the AAA+ motor of the proteasome (cyan), which initiates mechanical pulling, unfolding and movement of the protein into the proteasome's interior for cleavage into small shorter protein pieces called peptides. During movement of the substrate, its ubiquitin modification gets cleaved off by the deubiquitinase Rpn11 (green), which sits directly above the entrance to the AAA+ motor pore and acts as a gatekeeper to ensure efficient ubiquitin removal, a prerequisite for fast protein breakdown by the 26S proteasome. Related to video 3764.

Ribosomes are complex machines made up of more than 50 proteins and three or four strands of genetic material called ribosomal RNA (rRNA). The busy cellular machines make proteins, which are critical to almost every structure and function in the cell. To do so, they read protein-building instructions, which come as strands of messenger RNA. Ribosomes are found in all forms of cellular life—people, plants, animals, even bacteria. This illustration of a bacterial ribosome was produced using detailed information about the position of every atom in the complex. Several antibiotic medicines work by disrupting bacterial ribosomes but leaving human ribosomes alone. Scientists are carefully comparing human and bacterial ribosomes to spot differences between the two. Structures that are present only in the bacterial version could serve as targets for new antibiotic medications.

Rhodopsin is a pigment in the rod cells of the retina (back of the eye). It is extremely light-sensitive, supporting vision in low-light conditions. Here, it is attached to arrestin, a protein that sends signals in the body. This structure was determined using an X-ray free electron laser.

Glial cells (stained green) in a fruit fly developing embryo have survived thanks to a signaling pathway initiated by neighboring nerve cells (stained red).

A research mentor (Lori Eidson) and student (Nina Waldron, on the microscope) were 2009 members of the BRAIN (Behavioral Research Advancements In Neuroscience) program at Georgia State University in Atlanta. This program is an undergraduate summer research experience funded in part by NIGMS.

Peripheral nerve cells made from human embryonic stem cell-derived neural crest stem cells. The nuclei are shown in blue, and nerve cell proteins peripherin and beta-tubulin (Tuj1) are shown in green and red, respectively. Related to image 3264. Image is featured in October 2015 Biomedical Beat blog post Cool Images: A Halloween-Inspired Cell Collection.

The HIV capsid is a pear-shaped structure that is made of proteins the virus needs to mature and become infective. The capsid is inside the virus and delivers the virus' genetic information into a human cell. To better understand how the HIV capsid does this feat, scientists have used computer programs to simulate its assembly. This image shows a series of snapshots of the steps that grow the HIV capsid. A model of a complete capsid is shown on the far right of the image for comparison; the green, blue and red colors indicate different configurations of the capsid protein that make up the capsid “shell.” The bar in the left corner represents a length of 20 nanometers, which is less than a tenth the size of the smallest bacterium. Computer models like this also may be used to reconstruct the assembly of the capsids of other important viruses, such as Ebola or the Zika virus. The studies reporting this research were published in Nature Communications and Nature. To learn more about how researchers used computer simulations to track the assembly of the HIV capsid, see this press release from the University of Chicago.

This image is a computer-generated model of the approximately 4.2 million atoms of the HIV capsid, the shell that contains the virus' genetic material. Scientists determined the exact structure of the capsid and the proteins that it's made of using a variety of imaging techniques and analyses. They then entered these data into a supercomputer that produced the atomic-level image of the capsid. This structural information could be used for developing drugs that target the capsid, possibly leading to more effective therapies. Related to image 6601.

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

This image shows how the CRISPR surveillance complex is disabled by two copies of anti-CRISPR protein AcrF1 (red) and one AcrF2 (light green). These anti-CRISPRs block access to the CRISPR RNA (green tube) preventing the surveillance complex from scanning and targeting invading viral DNA for destruction.

This image shows the extracellular matrix (ECM) on the surface of a soleus (lower calf) muscle in light brown and blood vessels in pink. Near the bottom of the photo, a vessel is opened up to reveal red blood cells. Scientists know less about the ECM in muscle than in other tissues, but it's increasingly clear that the ECM is critical to muscle function, and disruption of the ECM has been associated with many muscle disorders. The ECM in muscles stores and releases growth factors, suggesting that it might play a role in cellular communication.

Many disease-causing microbes manipulate their host’s metabolism and cells for their own ends. Microsporidia—which are parasites closely related to fungi—infect and multiply inside animal cells, and take the rearranging of cells’ interiors to a new level. They reprogram animal cells such that the cells start to fuse, causing them to form long, continuous tubes. As shown in this image of the roundworm Caenorhabditis elegans, microsporidia (shown in magenta) have invaded the worm’s gut cells (shown in yellow; the cells’ nuclei are shown in blue) and have instructed the cells to merge. The cell fusion enables the microsporidia to thrive and propagate in the expanded space. Scientists study microsporidia in worms to gain more insight into how these parasites manipulate their host cells. This knowledge might help researchers devise strategies to prevent or treat infections with microsporidia. For more on the research into microsporidia, see this news release from the University of California San Diego. Related to images 5778 and 5779.

This image of human red blood cells was obtained with the help of a scanning electron microscope, an instrument that uses a finely focused electron beam to yield detailed images of the surface of a sample.

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.

To splice a human gene into a plasmid, scientists take the plasmid out of an E. coli bacterium, cut the plasmid with a restriction enzyme, and splice in human DNA. The resulting hybrid plasmid can be inserted into another E. coli bacterium, where it multiplies along with the bacterium. There, it can produce large quantities of human protein. See image 2565 for a labeled version of this illustration. Featured in The New Genetics.

You are face to face with a 6-day-old zebrafish larva. What look like eyes will become nostrils, and the bulges on either side will become eyes. Scientists use fast-growing, transparent zebrafish to see body shapes form and organs develop over the course of just a few days. Images like this one help researchers understand how gene mutations can lead to facial abnormalities such as cleft lip and palate in people.

This image won a 2016 FASEB BioArt award. In addition, NIH Director Francis Collins featured this on his blog on January 26, 2017.

Model of a member from the Tex protein family, which is implicated in transcriptional regulation and highly conserved in eukaryotes and prokaryotes. The structure shows significant homology to a human transcription elongation factor that may regulate multiple steps in mRNA synthesis.

During cell division, spindle pole bodies (glowing dots) move toward the ends of yeast cells to separate copied genetic information. Contractile rings (glowing bands) form in cells’ middles and constrict to help them split. This time-lapse video was captured using wide-field microscopy with deconvolution.

Related to images 6791, 6792, 6793, 6794, 6797, 6798, and video 6795.

Developing spermatids (precursors of mature sperm cells) begin as small, round cells and mature into long-tailed, tadpole-shaped ones. In the sperm cell's head is the cell nucleus; in its tail is the power to outswim thousands of competitors to fertilize an egg. As seen in this microscopy image, fruit fly spermatids start out as groups of interconnected cells. A small lipid molecule called PIP2 helps spermatids tell their heads from their tails. Here, PIP2 (red) marks the nuclei and a cell skeleton-building protein called tubulin (green) marks the tails. When PIP2 levels are too low, some spermatids get mixed up and grow with their heads at the wrong end. Because sperm development is similar across species, studies in fruit flies could help researchers understand male infertility in humans.

As an egg cell develops, a process called polarization controls what parts ultimately become the embryo's head and tail. This picture shows an egg of the fruit fly Drosophila. Red and green mark two types of signaling proteins involved in polarization. Disrupting these signals can scramble the body plan of the embryo, leading to severe developmental disorders.

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

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.

A blue laser beam turns on a protein that helps this human cancer cell move. Responding to the stimulus, the protein, called Rac1, first creates ruffles at the edge of the cell. Then it stretches the cell forward, following the light like a horse trotting after a carrot on a stick. This new light-based approach can turn Rac1 (and potentially many other proteins) on and off at exact times and places in living cells. By manipulating a protein that controls movement, the technique also offers a new tool to study embryonic development, nerve regeneration and cancer.

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

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

The receptor is shown bound to an inverse agonist, ZM241385.

Xenopus laevis, the African clawed frog, has long been used as a research organism for studying embryonic development. The abnormal presence of RNA encoding the signaling molecule plakoglobin causes atypical signaling, giving rise to a two-headed tadpole.

Three-dimensional reconstruction of a tubular matrix in a thin section of the peripheral endoplasmic reticulum between the plasma membranes of the cell.
The endoplasmic reticulum (ER) is a continuous membrane that extends like a net from the envelope of the nucleus outward to the cell membrane. The ER plays several roles within the cell, such as in protein and lipid synthesis and transport of materials between organelles.
Shown here are super-resolution microscopic images of the peripheral ER showing the structure of an ER tubular matrix between the plasma membranes of the cell. See image 5857 for a more detailed view of the area outlined in white in this image. For another view of the ER tubular matrix see image 5855

Protein kinases—enzymes that add phosphate groups to molecules—are cancer chemotherapy targets because they play significant roles in almost all aspects of cell function, are tightly regulated, and contribute to the development of cancer and other diseases if any alterations to their regulation occur. Genetic abnormalities affecting the c-Abl tyrosine kinase are linked to chronic myelogenous leukemia, a cancer of immature cells in the bone marrow. In the noncancerous form of the protein, binding of a myristoyl group to the kinase domain inhibits the activity of the protein until it is needed (top left shows the inactive form, top right shows the open and active form). The cancerous variant of the protein, called Bcr-Abl, lacks this autoinhibitory myristoyl group and is continually active (bottom). ATP is shown in green bound in the active site of the kinase.

Find these in the RCSB Protein Data Bank: c-Abl tyrosine kinase and regulatory domains (PDB entry 1OPL) and F-actin binding domain (PDB entry 1ZZP).

Staphylococcus aureus bacteria (green) grouping together upon contact with synovial fluid—a viscous substance found in joints. The formation of groups can help protect the bacteria from immune system defenses and from antibiotics, increasing the likelihood of an infection. This video is a 1-hour time lapse and was captured using a confocal laser scanning microscope.

More information about the research that produced this video can be found in the Journal of Bacteriology paper "In Vitro Staphylococcal Aggregate Morphology and Protection from Antibiotics Are Dependent on Distinct Mechanisms Arising from Postsurgical Joint Components and Fluid Motion" by Staats et al.

Related to images 6803 and 6804.

Like tractor-trailers on a highway, small sacs called vesicles transport substances within cells. This image tracks the motion of vesicles in a living cell. The short red and yellow marks offer information on vesicle movement. The lines spanning the image show overall traffic trends. Typically, the sacs flow from the lower right (blue) to the upper left (red) corner of the picture. Such maps help researchers follow different kinds of cellular processes as they unfold.

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.

The research organism Arabidopsis thaliana forms a large molecular machine called a resistosome to fight off infections. This illustration shows the top and side views of the fully-formed resistosome assembly (PDB entry 6J5T), composed of different proteins including one the plant uses as a decoy, PBL2 (dark blue), that gets uridylylated to begin the process of building the resistosome (uridylyl groups in magenta). Other proteins include RSK1 (turquoise) and ZAR1 (green) subunits. The ends of the ZAR1 subunits (yellow) form a funnel-like protrusion on one side of the assembly (seen in the side view). The funnel can carry out the critical protective function of the resistosome by inserting itself into the cell membrane to form a pore, which leads to a localized programmed cell death. The death of the infected cell helps protect the rest of the plant.

This image shows an abnormal, tetrapolar mitosis. Chromosomes are highlighted pink. The cells shown are S3 tissue cultured cells from Xenopus laevis, African clawed frog.

The molecule on the left is an electrostatic potential map of the van der Waals surface of the transition state for human purine nucleoside phosphorylase. The colors indicate the electron density at any position of the molecule. Red indicates electron-rich regions with negative charge and blue indicates electron-poor regions with positive charge. The molecule on the right is called DADMe-ImmH. It is a chemically stable analogue of the transition state on the left. It binds to the enzyme millions of times tighter than the substrate. This inhibitor is in human clinical trials for treating patients with gout. This image appears in Figure 4, Schramm, V.L. (2011) Annu. Rev. Biochem. 80:703-732.

Model of the mandelate racemase enzyme from Bacillus subtilis, a bacterium commonly found in soil.

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.

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. Regions without nuclei formed smaller compartments. Image created using epifluorescence microscopy.

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

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

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.

Taste buds in a mouse tongue epithelium with types I, II, and III taste cells visualized by cell-type-specific fluorescent antibodies. Type II taste bud cells signal sweet, bitter, and umami tastes to the central nervous system by releasing ATP through the voltage-gated ion channel CALHM1. Researchers used a confocal microscope to capture this image, which shows all taste buds in red, type II taste buds in green, and DNA in blue.

More information about this work can be found in the Nature letter "CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes” by Taruno et. al.