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.

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 mopping up.

Animation for the vesicular shuttle model of Golgi transport.

A mosquito larva with genes edited by CRISPR. The red-orange glow is a fluorescent protein used to track the edits. This species of mosquito, Culex quinquefasciatus, can transmit West Nile virus, Japanese encephalitis virus, and avian malaria, among other diseases. The researchers who took this image developed a gene-editing toolkit for Culex quinquefasciatus that could ultimately help stop the mosquitoes from spreading pathogens. The work is described in the Nature Communications paper "Optimized CRISPR tools and site-directed transgenesis towards gene drive development in Culex quinquefasciatus mosquitoes" by Feng et al. Related to image 6770 and video 6771.

Proteins are made of amino acids hooked end-to-end like beads on a necklace. To become active, proteins must twist and fold into their final, or "native," conformation. A protein's final shape enables it to accomplish its function. Featured in The Structures of Life.

Cells use bubble-like structures called vesicles (yellow) to import, transport, and export cargo and in cellular communication. A single cell may be filled with thousands of moving vesicles.

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

Motor neuron progenitors (green) were derived from human embryonic stem cells. Image and caption information courtesy of the California Institute for Regenerative Medicine.

This wreath represents the molecular structure of a protein, Cas4, which is part of a system, known as CRISPR, that bacteria use to protect themselves against viral invaders. The green ribbons show the protein's structure, and the red balls show the location of iron and sulfur molecules important for the protein's function. Scientists harnessed Cas9, a different protein in the bacterial CRISPR system, to create a gene-editing tool known as CRISPR-Cas9. Using this tool, researchers are able to study a range of cellular processes and human diseases more easily, cheaply and precisely. In December, 2015, Science magazine recognized the CRISPR-Cas9 gene-editing tool as the "breakthrough of the year." Read more about Cas4 in the December 2015 Biomedical Beat post A Holiday-Themed Image Collection.

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

Model of an enzyme, dUTP pyrophosphatase, from Mycobacterium tuberculosis. Drugs targeted to this enzyme might inhibit the replication of the bacterium that causes most cases of tuberculosis.

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.

DNA consists of two long, twisted chains made up of nucleotides. Each nucleotide contains one base, one phosphate molecule, and the sugar molecule deoxyribose. The bases in DNA nucleotides are adenine, thymine, cytosine, and guanine. See image 2541 for an unlabeled version of this illustration. Featured in The New Genetics.

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

This short video shows a model of the DNA helicase in yeast. This DNA helicase has 11 proteins that work together to unwind DNA during the process of copying it, called DNA replication. Scientists used a technique called cryo-electron microscopy (cryo-EM), which allowed them to study the helicase structure in solution rather than in static crystals. Cryo-EM in combination with computer modeling therefore allows researchers to see movements and other dynamic changes in the protein. The cryo-EM approach revealed the helicase structure at much greater resolution than could be obtained before. The researchers think that a repeated motion within the protein as shown in the video helps it move along the DNA strand. To read more about DNA helicase and this proposed mechanism, see this news release by Brookhaven National Laboratory.

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.

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.

This image shows a computer-generated, three-dimensional map of the rotavirus structure. This virus infects humans and other animals and causes severe diarrhea in infants and young children. By the age of five, almost every child in the world has been infected with this virus at least once. Scientists have found a vaccine against rotavirus, so in the United States there are very few fatalities, but in developing countries and in places where the vaccine is unavailable, this virus is responsible for more than 200,000 deaths each year.

The rotavirus comprises three layers: the outer, middle and inner layers. On infection, the outer layer is removed, leaving behind a "double-layered particle." Researchers have studied the structure of this double-layered particle with a transmission electron microscope. Many images of the virus at a magnification of ~50,000x were acquired, and computational analysis was used to combine the individual particle images into a three-dimensional reconstruction.

The image was rendered by Melody Campbell (PhD student at TSRI). Work that led to the 3D map was published in Campbell et al. Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure. 2012;20(11):1823-8. PMCID: PMC3510009.

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

A light organ (~0.5 mm across) of a Hawaiian bobtail squid, Euprymna scolopes, stained blue. At the time of this image, the crypts within the tissues of only one side of the organ had been colonized by green-fluorescent protein-labeled Vibrio fischeri cells, which can be seen here in green. This image was taken using confocal fluorescence microscopy.

Related to images 7016, 7017, 7018, and 7019.

This image integrates the thousands of known molecular and genetic interactions happening inside our bodies using a computer program called Cytoscape. Images like this are known as network wiring diagrams, but Cytoscape creator Trey Ideker somewhat jokingly calls them "hairballs" because they can be so complicated, intricate and hard to tease apart. Cytoscape comes with tools to help scientists study specific interactions, such as differences between species or between sick and diseased cells. Related to 2737.

From PDB entry 3c6k, Crystal structure of human spermine synthase in complex with spermidine and 5-methylthioadenosine.

A 3-D model of the alkaloid serratezomine A shows the molecule's complex ring structure.

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

The human genome contains much of the information needed for every cell in the body to function. However, different types of cells often need different types of information. Access to DNA is controlled, in part, by how tightly it’s wrapped around proteins called histones to form nucleosomes. The complex shown here, from yeast cells (PDB entry 6Z6P), includes several histone deacetylase (HDAC) enzymes (green and blue) bound to a nucleosome (histone proteins in red; DNA in yellow). The yeast HDAC enzymes are similar to the human enzymes. Two enzymes form a V-shaped clamp (green) that holds the other others, a dimer of the Hda1 enzymes (blue). In this assembly, Hda1 is activated and positioned to remove acetyl groups from histone tails.

Ribosomes manufacture proteins based on mRNA instructions. Each ribosome reads mRNA, recruits tRNA molecules to fetch amino acids, and assembles the amino acids in the proper order.

Dengue virus is a mosquito-borne illness that infects millions of people in the tropics and subtropics each year. Like many viruses, dengue is enclosed by a protective membrane. The proteins that span this membrane play an important role in the life cycle of the virus. Scientists used cryo-EM to determine the structure of a dengue virus at a 3.5-angstrom resolution to reveal how the membrane proteins undergo major structural changes as the virus matures and infects a host. The image shows a side view of the structure of a protein composed of two smaller proteins, called E and M. Each E and M contributes two molecules to the overall protein structure (called a heterotetramer), which is important for assembling and holding together the viral membrane, i.e., the shell that surrounds the genetic material of the dengue virus. The dengue protein's structure has revealed some portions in the protein that might be good targets for developing medications that could be used to combat dengue virus infections. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail. You can watch a rotating view of the dengue virus surface structure in video 3748.

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). This frame (4 out of 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, and find the full CRIPSR illustration here.

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 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 2570 and 2571.

Structure of sortase b from the bacterium B. anthracis, which causes anthrax. Sortase b is an enzyme used to rob red blood cells of iron, which the bacteria need to survive.

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. Featured in the March 2006, issue of Findings in "Viral Voyages."

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.

Cdc42, a member of the Rho family of small guanosine triphosphatase (GTPase) proteins, regulates multiple cell functions, including motility, proliferation, apoptosis, and cell morphology. In order to fulfill these diverse roles, the timing and location of Cdc42 activation must be tightly controlled. Klaus Hahn and his research group use special dyes designed to report protein conformational changes and interactions, here in living neutrophil cells. Warmer colors in this image indicate higher levels of activation. Cdc42 looks to be activated at cell protrusions.

Related to images 2451, 2452, and 2453.

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, a multivesicular body (the round structure slightly to the right of center) contain tiny intralumenal vesicles (with a diameter of only 25 nanometers; the round specks inside the larger round structure) adjacent to the cell's vacuole (below the multivesicular body, shown in darker and more uniform gray).

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 color-enhanced version 5767 and image 5769.

Cells progress through a cycle that consists of phases for growth (blue, green, yellow) and division (red). Cells become quiescent when they exit this cycle (purple). See image 2499 for a labeled version of this illustration.

This image shows the structure of a synapse, or junction between two nerve cells in three dimensions. From the brain of a mouse.

Meiosis is the process whereby a cell reduces its chromosomes from diploid to haploid in creating eggs or sperm. See image 2546 for a labeled version of this illustration. Featured in The New Genetics.

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 pig cell is in the process of dividing. The chromosomes (purple) have already replicated and the duplicates are being pulled apart by fibers of the cell skeleton known as microtubules (green). Studies of cell division yield knowledge that is critical to advancing understanding of many human diseases, including cancer and birth defects.

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

These smooth muscle cells were derived from mouse neural crest stem cells. Red indicates smooth muscle proteins, blue indicates nuclei. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Skins cells were reprogrammed into heart muscle cells. The cells highlighted in green are remaining skin cells. Red indicates a protein that is unique to heart muscle. The technique used to reprogram the skin cells into heart cells could one day be used to mend heart muscle damaged by disease or heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Colonies of bacteria growing despite high concentrations of antibiotics. These colonies are visible both by eye, as seen on the left, and by bioluminescence imaging, as seen on the right. The bioluminescent color indicates the metabolic activity of these bacteria, with their red centers indicating high metabolism.

More information about the research that produced this image can be found in the Antimicrobial Agents and Chemotherapy paper “Novel aminoglycoside-tolerant phoenix colony variants of Pseudomonas aeruginosa” by Sindeldecker et al.

A team of chemists and physicists used nanotechnology and DNA's ability to self-assemble with matching RNA to create a new kind of chip for measuring gene activity. When RNA of a gene of interest binds to a DNA tile (gold squares), it creates a raised surface (white areas) that can be detected by a powerful microscope. This nanochip approach offers manufacturing and usage advantages over existing gene chips and is a key step toward detecting gene activity in a single cell. Featured in the February 20, 2008, issue of Biomedical Beat.

Xenopus laevis, the African clawed frog, has long been used as a model organism for studying embryonic development. The frog embryo on the left lacks the developmental factor Sizzled. A normal embryo is shown on the right.

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.

A crystal of hen egg lysozyme protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

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.

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 3656. This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

A crystal of bacterial glucose isomerase protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.