The nucleolinus is a cellular compartment that has been a lonely bystander in scientific endeavors. Although it's found in a range of species, its function has been mysterious—mainly because the structure is hard to visualize. An August 2010 study showed that the nucleolinus is crucial for cell division. When researchers zapped the structure with a laser, an egg cell didn't complete division. When the oocyte was fertilized after laser microsurgery (bottom right), the resulting zygote didn't form vital cell division structures (blue and yellow).

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

Scanning electron micrograph of an apoptotic HeLa cell. Zeiss Merlin HR-SEM. See related images 3518, 3520, 3521, 3522.

Multiphoton fluorescence image of HeLa cells with cytoskeletal microtubules (magenta) and DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. See related images 3518, 3519, 3521, 3522.

Pigment cells are cells that give skin its color. In fishes and amphibians, like frogs and salamanders, pigment cells are responsible for the characteristic skin patterns that help these organisms to blend into their surroundings or attract mates. The pigment cells are derived from neural crest cells, which are cells originating from the neural tube in the early embryo. This image shows pigment cells called xanthophores in the skin of zebrafish; the cells glow (autofluoresce) brightly under light giving the fish skin a shiny, lively appearance. Investigating pigment cell formation and migration in animals helps answer important fundamental questions about the factors that control pigmentation in the skin of animals, including humans. Related to images 5754, 5756, 5757 and 5758.

Originally from the waters of India, Nepal, and neighboring countries, zebrafish can now be found swimming in science labs (and home aquariums) throughout the world. This fish is a favorite study subject for scientists interested in how genes guide the early stages of prenatal development (including the developing fin shown here) and in the effects of environmental contamination on embryos.

In this image, green fluorescent protein (GFP) is expressed where the gene sox9b is expressed. Collagen (red) marks the fin rays, and DNA, stained with a dye called DAPI, is in blue. sox9b plays many important roles during development, including the building of the heart and brain, and is also necessary for skeletal development. At the University of Wisconsin, researchers have found that exposure to contaminants that bind the aryl-hydrocarbon receptor results in the downregulation of sox9b. Loss of sox9b severely disrupts development in zebrafish and causes a life-threatening disorder called campomelic dysplasia (CD) in humans. CD is characterized by cardiovascular, neural, and skeletal defects. By studying the roles of genes such as sox9b in zebrafish, scientists hope to better understand normal development in humans as well as how to treat developmental disorders and diseases.

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

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.

Here, bubonic plague bacteria (yellow) are shown in the digestive system of a rat flea (purple). The bubonic plague killed a third of Europeans in the mid-14th century. Today, it is still active in Africa, Asia, and the Americas, with as many as 2,000 people infected worldwide each year. If caught early, bubonic plague can be treated with antibiotics.

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

Yeast cells with nuclear envelopes shown in magenta and tubulin shown in light blue. The nuclear envelope defines the borders of the nucleus, which houses DNA. Tubulin is a protein that makes up microtubules—strong, hollow fibers that provide structure to cells and help direct chromosomes during cell division. This image was captured using wide-field microscopy with deconvolution.

Related to images 6791, 6792, 6793, 6794, 6797, and videos 6795 and 6796.

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.

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.

This crystal structure shows a conserved hypothetical protein from Mycobacterium tuberculosis. Only 12 other proteins share its sequence homology, and none has a known function. This structure indicates the protein may play a role in metabolic pathways. Featured as one of the August 2007 Protein Structure Initiative Structures of the Month.

A light microscope image of cells 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 and have separated into the opposite sides of a dividing cell.

Related to images 1010, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, and 1021.

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

Pretty in pink, the enzyme histone deacetylase (HDA6) stands out against a background of blue-tinted DNA in the nucleus of an Arabidopsis plant cell. Here, HDA6 concentrates in the nucleolus (top center), where ribosomal RNA genes reside. The enzyme silences the ribosomal RNA genes from one parent while those from the other parent remain active. This chromosome-specific silencing of ribosomal RNA genes is an unusual phenomenon observed in hybrid plants.

Kupffer cells appear in the liver during the early stages of mammalian development and stay put throughout life to protect liver cells, clean up old red blood cells, and regulate iron levels. Source article Replenishing the Liver’s Immune Protections. Posted on December 12th, 2019 by Dr. Francis Collins.

The incredible complexity of a mammalian eye (in this case from a mouse) is captured here. Each color represents a different type of cell. In total, there are nearly 70 different cell types, including the retina's many rings and the peach-colored muscle cells clustered on the left.

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

HIV is a retrovirus, a type of virus that carries its genetic material not as DNA but as RNA. Long before anyone had heard of HIV, researchers in labs all over the world studied retroviruses, tracing out their life cycle and identifying the key proteins the viruses use to infect cells. When HIV was identified as a retrovirus, these studies gave AIDS researchers an immediate jump-start. The previously identified viral proteins became initial drug targets. See images 2513 and 2515 for other versions of this illustration. Featured in The Structures of Life.

Vibrio, a type (genus) of rod-shaped bacteria. Some Vibrio species cause cholera in humans.

Yeast make bread, beer, and wine. And like us, yeast can reproduce sexually. A mother and father cell fuse and create one large cell that contains four offspring. When environmental conditions are favorable, the offspring are released, as shown here. Yeast are also a popular study subject for scientists. Research on yeast has yielded vast knowledge about basic cellular and molecular biology as well as about myriad human diseases, including colon cancer and various metabolic disorders.

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

This image 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 image 5868 and video 5843

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. In this image, a cardiac muscle-restricted promoter drives firefly luciferase expression.
For imagery of both the lateral and overhead view go to 3556.
For imagery of the lateral view go to 3558.
For more information about the illumated area go to 3559.

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.

Each of the colored specs in this image is a cell on the surface of a fish scale. To better understand how wounds heal, scientists have inserted genes that make cells brightly glow in different colors into the skin cells of zebrafish, a fish often used in laboratory research. The colors enable the researchers to track each individual cell, for example, as it moves to the location of a cut or scrape over the course of several days. These technicolor fish endowed with glowing skin cells dubbed "skinbow" provide important insight into how tissues recover and regenerate after an injury.

For more information on skinbow fish, see the Biomedical Beat blog post Visualizing Skin Regeneration in Real Time and a press release from Duke University highlighting this research. Related to image 3783.

The TRPA1 protein is responsible for the burn you feel when you taste a bite of sushi topped with wasabi. Known therefore informally as the "wasabi receptor," this protein forms pores in the membranes of nerve cells that sense tastes or odors. Pungent chemicals like wasabi or mustard oil cause the pores to open, which then triggers a tingling or burn on our tongue. This receptor also produces feelings of pain in response to chemicals produced within our own bodies when our tissues are damaged or inflamed. Researchers used cryo-EM to reveal the structure of the wasabi receptor at a resolution of about 4 angstroms (a credit card is about 8 million angstroms thick). This detailed structure can help scientists understand both how we feel pain and how we can limit it by developing therapies to block the receptor. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail.

These cells are induced stem cells made from human adult skin cells that were genetically reprogrammed to mimic embryonic stem cells. The induced stem cells were made potentially safer by removing the introduced genes and the viral vector used to ferry genes into the cells, a loop of DNA called a plasmid. The work was accomplished by geneticist Junying Yu in the laboratory of James Thomson, a University of Wisconsin-Madison School of Medicine and Public Health professor and the director of regenerative biology for the Morgridge Institute for Research.

Yeast cells with endocytic actin patches (green). These patches help cells take in outside material. When a cell is in interphase, patches concentrate at its ends. During later stages of cell division, patches move to where the cell splits. This image was captured using wide-field microscopy with deconvolution.

Related to images 6791, 6792, 6794, 6797, 6798, and videos 6795 and 6796.

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

A colony of human embryonic stem cells (light blue) grows on fibroblasts (dark blue).

Ovarioles in female insects are tubes in which egg cells (called oocytes) form at one end and complete their development as they reach the other end of the tube. This image, taken with a confocal microscope, shows ovarioles in a very popular lab animal, the fruit fly Drosophila. The basic structure of ovarioles supports very rapid egg production, with some insects (like termites) producing several thousand eggs per day. Each insect ovary typically contains four to eight ovarioles, but this number varies widely depending on the insect species.

Scientists use insect ovarioles, for example, to study the basic processes that help various insects, including those that cause disease (like some mosquitos and biting flies), reproduce very quickly.

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.

Model of an enzyme, PanB, from Mycobacterium tuberculosis, the bacterium that causes most cases of tuberculosis. This enzyme is an attractive drug target.

These induced pluripotent stem cells (iPS cells) were derived from a woman's skin. Green and red indicate proteins found in reprogrammed cells but not in skin cells (TRA1-62 and NANOG). These cells can then develop into different cell types. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to image 3279.

Molecular model of the struture of heme. Heme is a small, flat molecule with an iron ion (dark red) at its center. Heme is an essential component of hemoglobin, the protein in blood that carries oxygen throughout our bodies. This image first appeared in the September 2013 issue of Findings Magazine. View side view of heme here 3540.

Moving protein or other molecules to specific cells to treat or examine them has been a major biological challenge. Scientists have now developed a technique for delivering chemicals to individual cells. The approach involves gold nanowires that, for example, can carry tumor-killing proteins. The advance was possible after researchers developed electric tweezers that could manipulate gold nanowires to help deliver drugs to single cells.

This movie shows the manipulation of the nanowires for drug delivery to a single cell. To learn more about this technique, see this post in the Computing Life series.

The extracellular matrix (ECM) is most prevalent in connective tissues but also is present between the stems (axons) of nerve cells. The axons of nerve cells are surrounded by the ECM encasing myelin-supplying Schwann cells, which insulate the axons to help speed the transmission of electric nerve impulses along the axons.

These neurons were derived from human embryonic stem cells. The neural cell bodies with axonal projections are visible in red, and the nuclei in blue. Some of the neurons have become dopaminergic neurons (yellow), the type that degenerate in people with Parkinson's disease. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to images 3270 and 3271.

Crystal structure of a protein with unknown function from Xanthomonas campestris, a plant pathogen. Eight copies of the protein crystallized to form a ring. Chosen as the December 2007 Protein Structure Initiative Structure of the Month.

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: image 1047, image 1048, image 1049,  image 1051 and image 1052.

Featured in the March 15, 2012 issue of Biomedical Beat. Related to Hsp33 Figure 2, image 3355.

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.

Cells in an early-stage fruit fly embryo, showing the DIAP1 protein (pink), an inhibitor of apoptosis.

Model of the catalytic portion of an enzyme, receptor-type tyrosine-protein phosphatase from humans. The enzyme consists of two identical protein subunits, shown in blue and green. The groups made up of purple and red balls represent phosphate groups, chemical groups that can influence enzyme activity. This phosphatase removes phosphate groups from the enzyme tyrosine kinase, counteracting its effects.

A global "map of the protein structure universe" indicating the positions of specific proteins. The preponderance of small, less-structured proteins near the origin, with the more highly structured, large proteins towards the ends of the axes, may suggest the evolution of protein structures.

In 2007, the FDA modified warfarin's label to indicate that genetic makeup may affect patient response to the drug. The widely used blood thinner is sold under the brand name Coumadin®. Scientists involved in the NIH Pharmacogenetics Research Network are investigating whether genetic information can be used to improve optimal dosage prediction for patients.

To become products, reactants must overcome an energy hill. See image 2526 for a labeled version of this illustration. Featured in The Chemistry of Health.

A drug's life in the body. Medicines taken by mouth pass through the liver before they are absorbed into the bloodstream. Other forms of drug administration bypass the liver, entering the blood directly. See 2528 for a labeled version of this illustration. Featured in Medicines By Design.

Atomic model of the membrane region of the mitochondrial ATP synthase built into a cryo-EM map at 3.6 Å resolution. ATP synthase is the primary producer of ATP in aerobic cells. Drugs that inhibit the bacterial ATP synthase, but not the human mitochondrial enzyme, can serve as antibiotics. This therapeutic approach was successfully demonstrated with the bedaquiline, an ATP synthase inhibitor now used in the treatment of extensively drug resistant tuberculosis.

More information about this structure can be found in the Science paper ”Atomic model for the dimeric F0 region of mitochondrial ATP synthase” by Guo et. al.

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.

Genes are often interrupted by stretches of DNA (introns, blue) that do not contain instructions for making a protein. The DNA segments that do contain protein-making instructions are known as exons (green). See image 2550 for an unlabeled version of this illustration. Featured in The New Genetics.