The center cluster of cells, colored blue, shows a colony of human embryonic stem cells. These cells, which arise at the earliest stages of development, are capable of differentiating into any of the 220 types of cells in the human body and can provide access to cells for basic research and potential therapies. This image is from the lab of the University of Wisconsin-Madison's James Thomson.

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.

Trypanosoma brucei is a single-cell parasite that causes sleeping sickness in humans. Scientists have been studying trypanosomes for some time because of their negative effects on human and also animal health, especially in sub-Saharan Africa. Moreover, because these organisms evolved on a separate path from those of animals and plants more than a billion years ago, researchers study trypanosomes to find out what traits they may harbor that are common to or different from those of other eukaryotes (i.e., those organisms having a nucleus and mitochondria). This image shows the T. brucei cell membrane in red, the DNA in the nucleus and kinetoplast (a structure unique to protozoans, including trypanosomes, which contains mitochondrial DNA) in blue and nuclear pore complexes (which allow molecules to pass into or out of the nucleus) in green. Scientists have found that the trypanosome nuclear pore complex has a unique mechanism by which it attaches to the nuclear envelope. In addition, the trypanosome nuclear pore complex differs from those of other eukaryotes because its components have a near-complete symmetry, and it lacks almost all of the proteins that in other eukaryotes studied so far are required to assemble the pore.

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool. This is the first frame in a series of four. 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).

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

The green in this image highlights a protein called TonB, which is produced by many gram-negative bacteria, including those that cause typhoid fever, meningitis and dysentery. TonB lets bacteria take up iron from the host's body, which they need to survive. More information about the research behind this image can be found in a Biomedical Beat Blog posting from August 2013.

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.

RNA incorporated into the CRISPR surveillance complex is positioned to scan across foreign DNA. Cryo-EM density from a 3Å reconstruction is shown as a yellow mesh.

This video shows a controlled outbreak of transmissible avian flu among people living in Thailand. Red indicates areas of infection while blue indicates areas where a combination of control measures were implemented. The video shows how control measures contained the infection in 90 days, before it spread elsewhere.

This network map shows molecular interactions (yellow) associated with a congenital condition that causes heart arrhythmias and the targets for drugs that alter these interactions (red and blue).

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.

The two large, central, round shapes are ovaries from a typical fruit fly (Drosophila melanogaster). The small butterfly-like structures surrounding them are fruit fly ovaries where researchers suppressed the expression of a gene that controls microtubule polymerization and is necessary for normal development. This image was captured using a confocal laser scanning microscope.

Related to image 6807.

Shiga toxin (green) is sorted from the endosome into membrane tubules (red), which then pinch off and move to the Golgi apparatus.

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, two multivesicular bodies (with yellow membranes) contain tiny intralumenal vesicles (with a diameter of only 25 nanometers; shown in red) adjacent to the cell's vacuole (in orange).

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 microscopy photograph 5768 that was used to generate this illustration and a zoomed-out version 5769 of this illustration.

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

These microscopic roundworms, called Caenorhabditis elegans, lack eyes and the opsin proteins used by visual systems to detect colors. However, researchers found that the worms can still sense the color of light in a way that enables them to avoid pigmented toxins made by bacteria. This image was captured using a stereo microscope.

To splice a human gene (in this case, the one for insulin) into a plasmid, scientists take the plasmid out of an E. coli bacterium, cut the plasmid with a restriction enzyme, and splice in insulin-making 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 insulin. See image 2564 for an unlabeled version of this illustration. Featured in The New Genetics.

Many researchers use the mouse (Mus musculus) as a model organism to study mammalian biology. Mice carry out practically all the same life processes as humans and, because of their small size and short generation times, are easily raised in labs. Scientists studying a certain cellular activity or disease can choose from tens of thousands of specially bred strains of mice to select those prone to developing certain tumors, neurological diseases, metabolic disorders, premature aging, or other conditions.

Solution NMR structure of protein target WR41 (left) from C. elegans. Noting the unanticipated structural similarity to the ubiquitin protein (Ub) found in all eukaryotic cells, researchers discovered that WR41 is a Ub-like modifier, ubiquitin-fold modifier 1 (Ufm1), on a newly uncovered ubiquitin-like pathway. Subsequently, the PSI group also determined the three-dimensional structure of protein target HR41 (right) from humans, the E2 ligase for Ufm1, using both NMR and X-ray crystallography.

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.

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.

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.

The G switch allows our bodies to respond rapidly to hormones. G proteins act like relay batons to pass messages from circulating hormones into cells. A hormone (red) encounters a receptor (blue) in the membrane of a cell. Next, a G protein (green) becomes activated and makes contact with the receptor to which the hormone is attached. Finally, the G protein passes the hormone's message to the cell by switching on a cell enzyme (purple) that triggers a response. See image 2536 and 2537 for other versions of this image. Featured in Medicines By Design.

This skyline of New York City was created by “printing” nanodroplets containing yeast (Saccharomyces cerevisiae) onto a large plate. Each dot is a separate yeast colony. As the colonies grew, a picture emerged, creating art. To make the different colors shown here, yeast strains were genetically engineered to produce pigments naturally made by bacteria, fungi, and sea creatures such as coral and sea anemones. Using genes from other organisms to make biological compounds paves the way toward harnessing yeast in the production of other useful molecules, from food to fuels and drugs.

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.

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

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 images 2491, 2494, and 2488.

What looks a little like distant planets with some mysterious surface features are actually assemblies of proteins normally found in the cell's nucleolus, a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from differences in how the proteins in each compartment mix with water and with each other. These differences let the proteins readily separate from each other into the three nucleolus compartments.

This photo of nucleolus proteins in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows each of the nucleolus compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue). The researchers have found that these compartments spontaneously fuse with each other on encounter without mixing with the other compartments.

For more details on this research, see this press release from Princeton. Related to video 3789, video 3791 and image 3792.

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. 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.

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.

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 red) have invaded the worm’s gut cells (the large blue dots are the cells' nuclei) 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 5777 and 5778.

This image shows two components of the cytoskeleton, microtubules (green) and actin filaments (red), in an endothelial cell derived from a cow lung. The cystoskeleton provides the cell with an inner framework and enables it to move and change shape.

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.

The molecules that glow blue in these cultured cells prevent the expression of the mutant proteins that cause Huntington's disease. Biochemist David Corey and others at UT Southwestern Medical Center designed the molecules to specifically target the genetic repeats that code for harmful proteins in people with Huntington's disese. People with Huntington's disease and similar neurodegenerative disorders often have extra copies of a gene segment. Moving from cell cultures to animals will help researchers further explore the potential of their specially crafted molecule to treat brain disorders. In addition to NIGMS, NIH's National Institute of Neurological Disorders and Stroke and National Institute of Biomedical Imaging and Bioengineering also funded this work.

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."

Using a supercomputer to simulate the movement of atoms in a ribosome, researchers looked into the core of this protein-making nanomachine and took snapshots. The picture shows an amino acid (green) being delivered by transfer RNA (yellow) into a corridor (purple) in the ribosome. In the corridor, a series of chemical reactions will string together amino acids to make a protein. The research project, which tracked the movement of more than 2.6 million atoms, was the largest computer simulation of a biological structure to date. The results shed light on the manufacturing of proteins and could aid the search for new antibiotics, which typically work by disabling the ribosomes of bacteria.

The G switch allows our bodies to respond rapidly to hormones. G proteins act like relay batons to pass messages from circulating hormones into cells. A hormone (red) encounters a receptor (blue) in the membrane of a cell. Next, a G protein (green) becomes activated and makes contact with the receptor to which the hormone is attached. Finally, the G protein passes the hormone's message to the cell by switching on a cell enzyme (purple) that triggers a response. See image 2536 and 2538 for other versions of this image. Featured in Medicines By Design.

Vibrio fischeri cells (~ 2 mm), labeled with green fluorescent protein (GFP), passing through a very narrow bottleneck in the tissues (red) of the Hawaiian bobtail squid, Euprymna scolopes, on the way to the crypts where the symbiont population resides. This image was taken using a confocal fluorescence microscope.

Although they are tiny, microbes that are growing in confined spaces can generate a lot of pressure. In this video, yeast cells grow in a small chamber called a microfluidic bioreactor. As the cells multiply, they begin to bump into and squeeze each other, resulting in periodic bursts of cells moving into different parts of the chamber. The continually growing cells also generate a lot of pressure--the researchers conducting these experiments found that the pressure generated by the cells can be almost five times higher than that in a car tire--about 150 psi, or 10 times the atmospheric pressure. Occasionally, this pressure even caused the small reactor to burst. By tracking the growth of the yeast or other cells and measuring the mechanical forces generated, scientists can simulate microbial growth in various places such as water pumps, sewage lines or catheters to learn how damage to these devices can be prevented. To learn more how researchers used small bioreactors to gauge the pressure generated by growing microbes, see this press release from UC Berkeley.

Microtubules (magenta) in neurons of the hippocampus, a part of the brain involved in learning and memory. Microtubules are strong, hollow fibers that provide structural support to cells. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6889, 6891, and 6892.

Zika virus is shown in cross section at center left. On the outside, it includes envelope protein (red) and membrane protein (magenta) embedded in a lipid membrane (light purple). Inside, the RNA genome (yellow) is associated with capsid proteins (orange). The viruses are shown interacting with receptors on the cell surface (green) and are surrounded by blood plasma molecules at the top.

The interior of a regenerating lizard tail 14 days after the original tail was amputated. Cell nuclei (blue), proliferating cells (green), cartilage (red), and muscle (white) have been visualized with immunofluorescence staining.

Adult Drosophila abdominal fat tissue showing cell nuclei labelled in magenta. The upper panel is from well-fed flies, and the lower panel is from flies that have been deprived of food for 4 hours. Starvation results in the accumulation of a key adipokine—a fat hormone (blue-green dots).

Related to images 6982, 6983, and 6985.

The plasma membrane is a cell's protective barrier. See image 2523 for an unlabeled version of this illustration. Featured in The Chemistry of Health.

Serum albumin (SA) is the most abundant protein in the blood plasma of mammals. SA has a characteristic heart-shape structure and is a highly versatile protein. It helps maintain normal water levels in our tissues and carries almost half of all calcium ions in human blood. SA also transports some hormones, nutrients and metals throughout the bloodstream. Despite being very similar to our own SA, those from other animals can cause some mild allergies in people. Therefore, some scientists study SAs from humans and other mammals to learn more about what subtle structural or other differences cause immune responses in the body.

Related to entries 3725 and 3675.

By attaching fluorescent proteins to the genetic circuit responsible for B. subtilis's stress response, researchers can observe the cells' pulses as green flashes. In response to a stressful environment like one lacking food, B. subtilis activates a large set of genes that help it respond to the hardship. Instead of leaving those genes on as previously thought, researchers discovered that the bacteria flip the genes on and off, increasing the frequency of these pulses with increasing stress. See entry 3254 for the related video.

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.

Automated crystal screening systems such as the one shown here are becoming a common feature at synchrotron and other facilities where high-throughput crystal structure determination is being carried out. These systems rapidly screen samples to identify the best candidates for further study.

Details about the basic biology and chemistry of the ingredients that produce bioluminescence are allowing scientists to harness it as an imaging tool. Credit: Nathan Shaner, Scintillon Institute.

From Biomedical Beat article July 2017: Chasing Fireflies—and Better Cellular Imaging Techniques

Ribbon diagram showing the structure of Ribonuclease P with tRNA.

Various views of a zebrafish head with blood vessels shown in purple. Researchers often study zebrafish because they share many genes with humans, grow and reproduce quickly, and have see-through eggs and embryos, which make it easy to study early stages of development.

This video was captured using a light sheet microscope.

Related to image 6934.