The green spots in this mouse brain are cells labeled with Calling Cards, a technology that records molecular events in brain cells as they mature. Understanding these processes during healthy development can guide further research into what goes wrong in cases of neuropsychiatric disorders. Also fluorescently labeled in this video are neurons (red) and nuclei (blue). Calling Cards and its application are described in the Cell paper “Self-Reporting Transposons Enable Simultaneous Readout of Gene Expression and Transcription Factor Binding in Single Cells” by Moudgil et al.; and the Proceedings of the National Academy of Sciences paper “A viral toolkit for recording transcription factor–DNA interactions in live mouse tissues” by Cammack et al. This video was created for the NIH Director’s Blog post The Amazing Brain: Tracking Molecular Events with Calling Cards.

Related to image 6780.

Floral pattern emerging as two bacterial species, motile Acinetobacter baylyi and non-motile Escherichia coli (green), are grown together for 72 hours on 0.5% 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 6553 for a photo of this process at 48 hours on 1% agar surface.
See 6555 for another photo of this process at 48 hours on 1% agar surface.
See 6550 for a video of this process.

Neuron from a crab showing the cell body (bottom), axon (rope-like extension), and growth cone (top right).

The nucleus of a human fibroblast cell with chromatin—a substance made up of DNA and proteins—shown in various colors. Fibroblasts are one of the most common types of cells in mammalian connective tissue, and they play a key role in wound healing and tissue repair. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6888 and 6893.

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 3741.

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 3793.

The receptor is shown bound to an antagonist, ML056.

Bacteria engineered to act as genetic clocks flash in synchrony. Here, a "supernova" burst in a colony of coupled genetic clocks just after reaching critical cell density. Superimposed: A diagram from the notebook of Christiaan Huygens, who first characterized synchronized oscillators in the 17th century.

The nucleus of a degenerating human tendon cell, also known as a tenocyte. It has been color-coded based on the density of chromatin—a substance made up of DNA and proteins. Areas of low chromatin density are shown in blue, and areas of high chromatin density are shown in red. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6887 and 6888.

These ripples of color represent the outer membrane of the nucleus inside an astrocyte, a star-shaped cell inside the brain. Some proteins (green) act as keys to unlock other proteins (red) that form gates to let small molecules in and out of the nucleus (blue). Visualizing these different cell components at the boundary of the astrocyte nucleus enables researchers to study the molecular and physiological basis of neurological disorders, such as hydrocephalus, a condition in which too much fluid accumulates in the brain, and scar formation in brain tissue leading to abnormal neuronal activity affecting learning and memory. Scientists have now identified a pathway may be common to many of these brain diseases and begun to further examine it to find ways to treat certain brain diseases and injuries.

A whole yeast (Saccharomyces cerevisiae) cell viewed by X-ray microscopy. Inside, the nucleus and a large vacuole (red) are visible.

Yeast cells that abnormally accumulate cell wall material (blue) at their ends and, when preparing to divide, in their middles. This image was captured using wide-field microscopy with deconvolution.

Related to images 6791, 6792, 6793, 6794, 6798, and videos 6795 and 6796.

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.

Related to images 1010, 1011, 1012, 1013, 1014, 1016, 1017, 1018, 1019, and 1021.

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.

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.

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool. This is the fifthframe in a series of five. 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 NIGMS Biomedical Beat blog entry, Field Focus: Precision Gene Editing with CRISPR and the iBiology video, Genome Engineering with CRISPR-Cas9: Birth of a Breakthrough Technology.

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.

Just 22 hours after fertilization, this zebrafish embryo is already taking shape. By 36 hours, all of the major organs will have started to form. The zebrafish's rapid growth and see-through embryo make it ideal for scientists studying how organs develop.

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

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.

Wound healing requires the action of stem cells. In mice that lack the Sept2/ARTS gene, stem cells involved in wound healing live longer and wounds heal faster and more thoroughly than in normal mice. This confocal microscopy image from a mouse lacking the Sept2/ARTS gene shows a tail wound in the process of healing. Cell nuclei are in blue. Red and orange mark hair follicle stem cells (hair follicle stem cells activate to cause hair regrowth, which indicates healing). See more information in the article in Science.

Phenylalanine tRNA showing the anticodon (yellow) and the amino acid, phenylalanine (blue and red spheres).

These time series show the heart rates of four different individuals. Automakers use steel scraps to build cars, construction companies repurpose tires to lay running tracks, and now scientists are reusing previously discarded medical data to better understand our complex physiology. Through a website called PhysioNet developed in part by Beth Israel Deaconess Medical Center cardiologist Ary Goldberger, scientists can access complete physiologic recordings, such as heart rate, respiration, brain activity and gait. They then can use free software to analyze the data and find patterns in it. The patterns could ultimately help health care professionals diagnose and treat health conditions like congestive heart failure, sleeping disorders, epilepsy and walking problems. PhysioNet is supported by NIH's National Institute of Biomedical Imaging and Bioengineering as well as by NIGMS.

This scanning electron microscope (SEM) image shows podocytes--cells in the kidney that play a vital role in filtering waste from the bloodstream--from a patient with chronic kidney disease. This image first appeared in Princeton Journal Watch on October 4, 2013.

This Petri dish contains microscopic roundworms called Caenorhabditis elegans. Researchers used these particular worms to study how C. elegans senses the color of light in its environment.

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). In ARPC3-/- fibroblast cells, mDia1 is localized at the tips of the filopodia-like structures. Related to images 3328, 3329, 3330, 3332, and 3333.

Just as our bodies rely on bones for structural support, our cells rely on a cellular skeleton. In addition to helping cells keep their shape, this cytoskeleton transports material within cells and coordinates cell division. One component of the cytoskeleton is a protein called tubulin, shown here as thin strands.

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

This video shows an instance of abnormal mitosis where chromosomes are late to align. The video demonstrates the spindle checkpoint in action: just one unaligned chromosome can delay anaphase and the completion of mitosis. The cells shown are S3 tissue cultured cells from Xenopus laevis, African clawed frog.

During mitosis, spindle microtubules (red) attach to chromosome pairs (blue), directing them to the spindle equator. This midline alignment is critical for equal distribution of chromosomes in the dividing cell. Scientists are interested in how the protein kinase Plk1 (green) regulates this activity in human cells. Image is a volume projection of multiple deconvolved z-planes acquired with a Nikon widefield fluorescence microscope. This image was chosen as a winner of the 2016 NIH-funded research image call. Related to image 5766.

The research that led to this image was funded by NIGMS.

Animation for the cisternae maturation model of Golgi transport.

Many of today's medicines come from products found in nature, such as this sponge found off the coast of Palau in the Pacific Ocean. Chemists have synthesized a compound called Palau'amine, which appears to act against cancer, bacteria and fungi. In doing so, they invented a new chemical technique that will empower the synthesis of other challenging molecules.

Various views of a mouse brain that was genetically modified so that subpopulations of its neurons glow. Researchers often study mice because they share many genes with people and can shed light on biological processes, development, and diseases in humans.

This video was captured using a light sheet microscope.

Related to images 6929 and 6930.

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.

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

Two fruit fly (Drosophila melanogaster) larvae brains with neurons expressing fluorescently tagged tubulin protein. Tubulin makes up strong, hollow fibers called microtubules that play important roles in neuron growth and migration during brain development. This image was captured using confocal microscopy, and the color indicates the position of the neurons within the brain.

The chemical structure of the morphine molecule

A segment of siRNA, shown in red, guides a "slicer" protein called Argonaute (multi-colored twists and corkscrews) to the target RNA molecules.

Disassembly of vasculature and reassembly after addition and then washout of 250 µM TBZ in kdr:GFP frogs. Related to images 3403 and 3404.

A knotted protein from an archaebacterium called Methanobacterium thermoautotrophicam. This organism breaks down waste products and produces methane gas. Protein folding theory previously held that forming a knot was beyond the ability of a protein, but this structure, determined at Argonne's Structural Biology Center, proves differently. Researchers theorize that this knot stabilizes the amino acid subunits of the protein.

E. coli bacteria normally live harmlessly in our intestines, but some cause disease by making toxins. One of these toxins, called Shiga toxin (green), inactivates host ribosomes (purple) by mimicking their normal binding partners, the EF-Tu elongation factor (red) complexed with Phe-tRNAPhe (orange).

Find these in the RCSB Protein Data Bank: Shiga toxin 2 (PDB entry 7U6V) and Phe-tRNA (PDB entry 1TTT).

More information about this work can be found in the J. Biol. Chem. paper "Cryo-EM structure of Shiga toxin 2 in complex with the native ribosomal P-stalk reveals residues involved in the binding interaction" by Kulczyk et. al.

The atomic structure of the morphine biosynthetic enzyme salutaridine reductase bound to the cofactor NADPH. The substrate salutaridine is shown entering the active site.

Researchers used fluorescence in situ hybridization (FISH) to confirm the presence of long range DNA-DNA interactions in mouse embryonic stem cells. Here, two loci labeled in green (Oct4) and red that are 13 Mb apart on linear DNA are frequently found to be in close proximity. DNA-DNA colocalizations like this are thought to both reflect and contribute to cell type specific gene expression programs.

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, 2495, and 2488.

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.

This image shows a cell in two stages of division: prometaphase (top) and metaphase (bottom). To form identical daughter cells, chromosome pairs (blue) separate via the attachment of microtubules made up of tubulin proteins (pink) to specialized structures on centromeres (green).

Multiple actin filaments (magenta) are organized around a dynamin helical polymer (rainbow colored) in this model derived from cryo-electron tomography. By bundling actin, dynamin increases the strength of a cell’s skeleton and plays a role in cell-cell fusion, a process involved in conception, development, and regeneration.

Scientists use nuclear magnetic spectroscopy (NMR) to determine the detailed, 3D structures of molecules.

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.

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 process involves significant shape changes on the part of the nurse cells (blue), which are powered by wavelike activity of the protein myosin (red). This image was captured using a confocal laser scanning microscope. Related to video 6754.

What looks like a Native American dream catcher is really a network of social interactions within a community. The red dots along the inner and outer circles represent people, while the different colored lines represent direct contact between them. All connections originate from four individuals near the center of the graph. Modeling social networks can help researchers understand how diseases spread.