T cells are white blood cells that are important in defending the body against bacteria, viruses and other pathogens. Each T cell carries proteins, called T-cell receptors, on its surface that are activated when they come in contact with an invader. This activation sets in motion a cascade of biochemical changes inside the T cell to mount a defense against the invasion. Scientists have been interested for some time what happens after a T-cell receptor is activated. One obstacle has been to study how this signaling cascade, or pathway, proceeds inside T cells.

In this image, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The image shows two key steps during the signaling process: clustering of a protein called linker for activation of T cells (LAT) (blue) and polymerization of the cytoskeleton protein actin (red). The findings show that the T-cell receptor signaling proteins self-organize into separate physical and biochemical compartments. This new system of studying molecular pathways outside the cells will enable scientists to better understand how the immune system combats microbes or other agents that cause infection.

To learn more how researchers assembled this T-cell receptor pathway, see this press release from HHMI's Marine Biological Laboratory Whitman Center. Related to video 3786.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to images 3413, 3414, 3415, 3416, 3418, and 3419.

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

Early on, this Arabidopsis plant embryo picks sides: While one end will form the shoot, the other will take root underground. Short pieces of RNA in the bottom half (blue) make sure that shoot-forming genes are expressed only in the embryo's top half (green), eventually allowing a seedling to emerge with stems and leaves. Like animals, plants follow a carefully orchestrated polarization plan and errors can lead to major developmental defects, such as shoots above and below ground. Because the complex gene networks that coordinate this development in plants and animals share important similarities, studying polarity in Arabidopsis--a model organism--could also help us better understand human development.

This image captures the spiral-shaped ovary of an anglerfish in cross-section. Once matured, these eggs will be released in a gelatinous, floating mass. For some species of anglerfish, this egg mass can be up to 3 feet long and include nearly 200,000 eggs.

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

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.

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

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.

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.

It has been said that gastrulation is the most important event in a person's life. This part of early embryonic development transforms a simple ball of cells and begins to define cell fate and the body axis. In a study published in Science magazine, NIGMS grantee Bob Goldstein and his research group studied how contractions of actomyosin filaments in C. elegans and Drosophila embryos lead to dramatic rearrangements of cell and embryonic structure. In these images, myosin (green) and plasma membrane (red) are highlighted at four timepoints in gastrulation in the roundworm C. elegans. The blue highlights in the top three frames show how cells are internalized, and the site of closure around the involuting cells is marked with an arrow in the last frame. See related image 3297.

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.

A number of environmental factors cause DNA mutations that can lead to cancer: toxins in cigarette smoke, sunlight and other radiation, and some viruses.

Cilia (cilium in singular) are complex molecular machines found on many of our cells. One component of cilia is the doublet microtubule, a major part of cilia’s skeletons that give them support and shape. This animated image is a partial model of a doublet microtubule’s structure based on cryo-electron microscopy images. Video can be found here 6549.

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.

In the absence of the engulfment receptor Draper, salivary gland cells (light blue) persist in the thorax of a developing Drosophila melanogaster pupa. See image 2758 for a cross section of a normal pupa that does express Draper.

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

Stained cross section of a mouse tail.

Learn about basic science, sometimes called “pure” or “fundamental” science, and how it contributes to the development of medical treatments. Discover more resources from NIGMS’ Pathways collaboration with Scholastic. View the video on YouTube for closed captioning.

Mitosis creates cells, and apoptosis kills them. The processes often work together to keep us healthy.

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 2514 for other versions of this illustration. Featured in The Structures of Life.

New research shows telomeres moving to the outer edge of the nucleus after cell division, suggesting these caps that protect chromosomes also may play a role in organizing DNA.

Crystals of jack bean concanavalin A protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

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.

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.

The plasma membrane is a cell's protective barrier. See image 2524 for a labeled version of this illustration. Featured in The Chemistry of Health.

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.

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.

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 image was captured using a light sheet microscope.

Related to image 6930 and video 6931.

A Trigonium diatom imaged by a quantitative orientation-independent differential interference contrast (OI-DIC) microscope. Diatoms are single-celled photosynthetic algae with mineralized cell walls that contain silica and provide protection and support. These organisms form an important part of the plankton at the base of the marine and freshwater food chains. The width of this image is 90 μm.

More information about the microscopy that produced this image can be found in the Journal of Microscopy paper “An Orientation-Independent DIC Microscope Allows High Resolution Imaging of Epithelial Cell Migration and Wound Healing in a Cnidarian Model” by Malamy and Shribak.

Stained kidney tissue. The kidney is an essential organ responsible for disposing wastes from the body and for maintaining healthy ion levels in the blood. It also secretes two hormones, erythropoietin (EPO) and calcitriol (a derivative of vitamin D), into the blood. It works like a purifier by pulling break-down products of metabolism, such as urea and ammonium, from the blood stream for excretion in urine. Related to image 3725.

Composite image of beta-galactosidase showing how cryo-EM’s resolution has improved dramatically in recent years. Older images to the left, more recent to the right. Related to image 5882. NIH Director Francis Collins featured this on his blog on January 14, 2016.

This image shows an osteosarcoma cell with DNA in blue, energy factories (mitochondria) in yellow, and actin filaments—part of the cellular skeleton—in purple. One of the few cancers that originate in the bones, osteosarcoma is rare, with about a thousand new cases diagnosed each year in the United States.

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

Like a watch wrapped around a wrist, a special enzyme encircles the double helix to repair a broken strand of DNA. Without molecules that can mend such breaks, cells can malfunction, die, or become cancerous. Related to image 3493.

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.

Microtubules in African green monkey cells. Microtubules are strong, hollow fibers that provide cells with structural support. Here, the microtubules have been color-coded based on their distance from the microscope lens: purple is closest to the lens, and yellow is farthest away. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6889, 6890, and 6892.

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 protein N-cadherin, which indicates normal connections between cells. 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 3283.

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). In this frame (2 of 4), the CRISPR machine locates the target DNA sequence once inserted into a cell.

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

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 2571 and 2572.

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

In the gene-editing tool CRISPR, a small strand of RNA identifies a specific chunk of DNA. Then the enzyme Cas9 (green) swoops in and cuts the double-stranded DNA (blue/purple) in two places, removing the specific chunk.

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.

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.

Reactivating telomerase in our cells does not appear to be a good way to extend the human lifespan. Cancer cells reactivate telomerase.

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.

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.

A model of the molecule himastatin overlaid on an image of Bacillus subtilis bacteria. Scientists first isolated himastatin from the bacterium Streptomyces himastatinicus, and the molecule shows antibiotic activity. The researchers who created this image developed a new, more concise way to synthesize himastatin so it can be studied more easily. They also tested the effects of himastatin and derivatives of the molecule on B. subtilis.

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

Related to image 6848 and video 6851.

The human skin cells pictured contain genetic modifications that make them pluripotent, essentially equivalent to embryonic stem cells. A scientific team from the University of Wisconsin-Madison including researchers Junying Yu, James Thomson, and their colleagues produced the transformation by introducing a set of four genes into human fibroblasts, skin cells that are easy to obtain and grow in culture.

X-ray structure of a DNA repair enzyme superfamily representative from the human gastrointestinal bacterium Enterococcus faecalis. European scientists used this structure to generate homologous structures. Featured as the May 2007 Protein Structure Initiative Structure of the Month.