A protein called tubulin (green) accumulates in the center of a nucleus (outlined in pink) from an aging cell. Normally, this protein is kept out of the nucleus with the help of gatekeepers known as nuclear pore complexes. But NIGMS-funded researchers found that wear and tear to long-lived components of the complexes eventually lowers the gatekeepers' guard. As a result, cytoplasmic proteins like tubulin gain entry to the nucleus while proteins normally confined to the nucleus seep out. The work suggests that finding ways to stop the leakage could slow the cellular aging process and possibly lead to new therapies for age-related diseases.

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

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.

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 receptor is shown bound to an antagonist, JDTic.

Leptospira, shown here in green, is a type (genus) of elongated, spiral-shaped bacteria. Infection can cause Weil's disease, a kind of jaundice, in humans.

Irina Dementieva, a biochemist, and Youngchang Kim, a biophysicist and crystallographer, work with the first robot of its type in the U.S. to automate protein purification. The robot, which is housed in a refrigerator, is an integral part of the Midwest Structural Genomics Center's plan to automate the protein crystallography process.

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.

A 3D reconstruction of a transient receptor potential channel called TRPV5 that was created based on cryo-electron microscopy images. TRPV5 is primarily found in kidney cells and is essential for reabsorbing calcium into the blood.

Stereo triplet of a sea urchin embryo stained to reveal actin filaments (orange) and microtubules (blue). This image is part of a series of images: 1047, 1048, 1049, 1050 and 1051.

Learn how research organisms, such as fruit flies and mice, can help us understand and treat human diseases. Discover more resources from NIGMS’ Pathways collaboration with Scholastic. View the video on YouTube for closed captioning.

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.

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 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.

Like a strand of white pearls, DNA wraps around an assembly of special proteins called histones (colored) to form the nucleosome, a structure responsible for regulating genes and condensing DNA strands to fit into the cell's nucleus. Researchers once thought that nucleosomes regulated gene activity through their histone tails (dotted lines), but a 2010 study revealed that the structures' core also plays a role. The finding sheds light on how gene expression is regulated and how abnormal gene regulation can lead to cancer.

This microscopic image shows a chromatin fiber--a DNA molecule bound to naturally occurring proteins.

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Cells are connected to one another by their cell walls, shown in blue. Stained cytoplasm (green) and membranes (magenta) show that the individual cells remain separate. This image was captured using spinning disk confocal microscopy.

Related to images 6969 and 6971.

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 2495.

This fiery image doesn’t come from inside a bubbling volcano. Instead, it shows animal cells caught in the act of making bubbles, or blebbing. Some cells regularly pinch off parts of their membranes to produce bubbles filled with a mix of proteins and fats. The bubbles (red) are called plasma-derived membrane vesicles, or PMVs, and can travel to other parts of the body where they may aid in cell-cell communication. The University of Texas, Austin, researchers responsible for this photo are exploring ways to use PMVs to deliver medicines to precise locations in the body.

This image, entered in the Biophysical Society’s 2017 Art of Science Image contest, used two-channel spinning disk confocal fluorescence microscopy. It was also featured in the NIH Director’s Blog in May 2017.

Real-time footage of Caenorhabditis elegans, a tiny roundworm, trapped by a carnivorous fungus, Arthrobotrys dactyloides. This fungus makes ring traps in response to the presence of C. elegans. When a worm enters a ring, the trap rapidly constricts so that the worm cannot move away, and the fungus then consumes the worm. The size of the imaged area is 0.7mm x 0.9mm.

This video was obtained with a polychromatic polarizing microscope (PPM) in white light that shows the polychromatic birefringent image with hue corresponding to the slow axis orientation. More information about PPM can be found in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak.

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.

Los ritmos circadianos son cambios físicos, mentales y de comportamiento que siguen un ciclo de 24 horas. Los ritmos circadianos se ven influenciados por la luz y están regulados por el núcleo supraquiasmático del cerebro, a veces denominado el reloj principal.

Vea 6613 para la versión en inglés de esta infografía.

Human embryonic stem cells differentiated into dopaminergic neurons, the type that degenerate in Parkinson's disease. Image courtesy of the California Institute for Regenerative Medicine. Related to images 3271 and 3285.

Nerve cells have long, invisibly thin fibers that carry electrical impulses throughout the body. Some of these fibers extend about 3 feet from the spinal cord to the toes.

Bioengineers were able to coax bacteria to blink in unison on microfluidic chips. They called each blinking bacterial colony a biopixel. Thousands of fluorescent E. coli bacteria, shown here, make up a biopixel. Related to images 3265 and 3266. From a UC San Diego news release, "Researchers create living 'neon signs' composed of millions of glowing bacteria."

Real-time movie of young squids. Squids are often used as research organisms due to having the largest nervous system of any invertebrate, complex behaviors like instantaneous camouflage, and other unique traits.

This video was taken with polychromatic polarization microscope, as described in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak. The color is generated by interaction of white polarized light with the squid’s transparent soft tissue. The tissue works as a living tunable spectral filter, and the transmission band depends on the molecular orientation. When the young squid is moving, the tissue orientation changes, and its color shifts accordingly.

This video results from a research project to visualize which regions of the adult fruit fly (Drosophila) brain derive from each neural stem cell. First, researchers collected several thousand fruit fly larvae and fluorescently stained a random stem cell in the brain of each. The idea was to create a population of larvae in which each of the 100 or so neural stem cells was labeled at least once. When the larvae grew to adults, the researchers examined the flies’ brains using confocal microscopy. With this technique, the part of a fly’s brain that derived from a single, labeled stem cell “lights up.” The scientists photographed each brain and digitally colorized its lit-up area. By combining thousands of such photos, they created a three-dimensional, color-coded map that shows which part of the Drosophila brain comes from each of its ~100 neural stem cells. In other words, each colored region shows which neurons are the progeny or “clones” of a single stem cell. This work established a hierarchical structure as well as nomenclature for the neurons in the Drosophila brain. Further research will relate functions to structures of the brain.

Related to images 5838 and 5868.

A zebrafish embryo showing its natural colors. Zebrafish have see-through eggs and embryos, making them ideal research organisms for studying the earliest stages of development. This image was taken in transmitted light under a polychromatic polarizing microscope.

Arranging exons in different patterns, called alternative splicing, enables cells to make different proteins from a single gene. Featured in The New Genetics.

See image 2552 for an unlabeled version of this illustration.

DNA (blue) and actin (red) in cultured fibroblast cells.

A microtubule, part of the cell's skeleton, builds and deconstructs.

The "epigenetic code" controls gene activity with chemical tags that mark DNA (purple diamonds) and the "tails" of histone proteins (purple triangles). These markings help determine whether genes will be transcribed by RNA polymerase. Genes hidden from access to RNA polymerase are not expressed. See image 2563 for a labeled version of this illustration. Featured in The New Genetics.

Two healthy cells (bottom, left) enter into apoptosis (bottom, center) but spring back to life after a fatal toxin is removed (bottom, right; top).

A genetic disorder of the nervous system, neurofibromatosis causes tumors to form on nerves throughout the body, including a type of tumor called an optic nerve glioma that can result in childhood blindness. The image was used to demonstrate the unique imaging capabilities of one of our newest (at the time) laser scanning microscopes and is of a wildtype (normal) mouse retina in the optic fiber layer. This layer is responsible for relaying information from the retina to the brain and was fluorescently stained to reveal the distribution of glial cells (green), DNA and RNA in the cell bodies of the retinal ganglion neurons (orange) and their optic nerve fibers (red), and actin in endothelial cells surrounding a prominent branching blood vessel (blue). By studying the microscopic structure of normal and diseased retina and optic nerves, we hope to better understand the altered biology of the tissues in these tumors with the prospects of developing therapeutic interventions.

This structure from an amyloid-forming prion protein shows one way beta sheets can stack. Image originally appeared in a December 2012 PLOS Biology paper.

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 2572.

The nuclei stained green highlight human embryonic stem cells grown under controlled conditions in a laboratory. Blue represents the DNA of surrounding, supportive feeder cells. Image and caption information courtesy of the California Institute for Regenerative Medicine. See related image 3724.

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 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.

The endoplasmic reticulum comes in two types: Rough ER is covered with ribosomes and prepares newly made proteins; smooth ER specializes in making lipids and breaking down toxic molecules.

3D reconstructions of two stages in the assembly of the bacterial ribosome created from time-resolved cryo-electron microscopy images. Ribosomes translate genetic instructions into proteins.

Both instruments shown were developed by CellFree Sciences of Yokohama, Japan. The instrument on the left, the GeneDecoder 1000, can generate 384 proteins from their corresponding genes, or gene fragments, overnight. It is used to screen for properties such as level of protein production and degree of solubility. The instrument on the right, the Protemist Protein Synthesizer, is used to generate the larger amounts of protein needed for protein structure determinations.

Catalases are some of the most efficient enzymes found in cells. Each catalase molecule can decompose millions of hydrogen peroxide molecules every second—working as an antioxidant to protect cells from the dangerous form of reactive oxygen. Different cells build different types of catalases. The human catalase that protects our red blood cells, shown on the left from PDB entry 1QQW, is composed of four identical subunits and uses a heme/iron group to perform the reaction. Many bacteria scavenge hydrogen peroxide with a larger catalase, shown in the center from PDB entry 1IPH, that uses a similar arrangement of iron and heme. Other bacteria protect themselves with an entirely different catalase that uses manganese ions instead of heme, as shown at the right from PDB entry 1JKU.

A study published in March 2012 used cryo-electron microscopy to determine the structure of the DNA replication origin recognition complex (ORC), a semi-circular, protein complex (yellow) that recognizes and binds DNA to start the replication process. The ORC appears to wrap around and bend approximately 70 base pairs of double stranded DNA (red and blue). Also shown is the protein Cdc6 (green), which is also involved in the initiation of DNA replication. The video shows the structure from different angles. See related image 3597.

Model of a major secreted protein of unknown function, which is only found in mycobacteria, the class of bacteria that causes tuberculosis. Based on structural similarity, this protein may be involved in host-bacterial interactions.

This fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.

This image shows neonatal mouse heart cells. These cells were grown in the lab on a chip that aligns the cells in a way that mimics what is normally seen in the body. Green shows the muscle protein toponin I. Red indicates the muscle protein actin, and blue indicates the cell nuclei. The work shown here was part of a study attempting to grow heart tissue in the lab to repair damage after a heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to images 3281 and 3282.

Structure of the bacterial antitoxin protein GhoS. GhoS inhibits the production of a bacterial toxin, GhoT, which can contribute to antibiotic resistance. GhoS is the first known bacterial antitoxin that works by cleaving the messenger RNA that carries the instructions for making the toxin. More information can be found in the paper: Wang X, Lord DM, Cheng HY, Osbourne DO, Hong SH, Sanchez-Torres V, Quiroga C, Zheng K, Herrmann T, Peti W, Benedik MJ, Page R, Wood TK. A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol. 2012 Oct;8(10):855-61. Related to 3427.

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.

A 360-degree view of the molecule himastatin, which was first isolated from the bacterium Streptomyces himastatinicus. Himastatin shows antibiotic activity. The researchers who created this video developed a new, more concise way to synthesize himastatin so it can be studied more easily.

More information about the research that produced this video can be found in the Science paper “Total synthesis of himastatin” by D’Angelo et al.

Related to images 6848 and 6850.