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.

A blue laser beam turns on a protein that helps this human cancer cell move. Responding to the stimulus, the protein, called Rac1, first creates ruffles at the edge of the cell. Then it stretches the cell forward, following the light like a horse trotting after a carrot on a stick. This new light-based approach can turn Rac1 (and potentially many other proteins) on and off at exact times and places in living cells. By manipulating a protein that controls movement, the technique also offers a new tool to study embryonic development, nerve regeneration and cancer.

Cell-like compartments that spontaneously emerged from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Regions without nuclei formed smaller compartments. Image created using epifluorescence microscopy.

For more photos of cell-like compartments from frog eggs view: 6584, 6586, 6591, 6592, and 6593.

For videos of cell-like compartments from frog eggs view: 6587, 6588, 6589, and 6590.

The receptor is shown bound to a small molecule peptide called CVX15.

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.

A biofilm is a highly organized community of microorganisms that develops naturally on certain surfaces. These communities are common in natural environments and generally do not pose any danger to humans. Many microbes in biofilms have a positive impact on the planet and our societies. Biofilms can be helpful in treatment of wastewater, for example. This dime-sized biofilm, however, was formed by the opportunistic pathogen Pseudomonas aeruginosa. Under some conditions, this bacterium can infect wounds that are caused by severe burns. The bacterial cells release a variety of materials to form an extracellular matrix, which is stained red in this photograph. The matrix holds the biofilm together and protects the bacteria from antibiotics and the immune system.

As an egg cell develops, a process called polarization controls what parts ultimately become the embryo's head and tail. This picture shows an egg of the fruit fly Drosophila. Red and green mark two types of signaling proteins involved in polarization. Disrupting these signals can scramble the body plan of the embryo, leading to severe developmental disorders.

These images model the molecular structures of three enzymes with critical roles in the life cycle of the human immunodeficiency virus (HIV). At the top, reverse transcriptase (orange) creates a DNA copy (yellow) of the virus's RNA genome (blue). In the middle image, integrase (magenta) inserts this DNA copy in the DNA genome (green) of the infected cell. At the bottom, much later in the viral life cycle, protease (turquoise) chops up a chain of HIV structural protein (purple) to generate the building blocks for making new viruses. See these enzymes in action on PDB 101’s video A Molecular View of HIV Therapy.

The Golgi complex, also called the Golgi apparatus or, simply, the Golgi. This organelle receives newly made proteins and lipids from the ER, puts the finishing touches on them, addresses them, and sends them to their final destinations.

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.

Influenza A infects a host cell when hemagglutinin grips onto glycans on its surface. Neuraminidase, an enzyme that chews sugars, helps newly made virus particles detach so they can infect other cells. Related to 213.

Like a pulsing blue shower, E. coli cells flash in synchrony. Genes inserted into each cell turn a fluorescent protein on and off at regular intervals. When enough cells grow in the colony, a phenomenon called quorum sensing allows them to switch from blinking independently to blinking in unison. Researchers can watch waves of light propagate across the colony. Adjusting the temperature, chemical composition or other conditions can change the frequency and amplitude of the waves. Because the blinks react to subtle changes in the environment, synchronized oscillators like this one could one day allow biologists to build cellular sensors that detect pollutants or help deliver drugs.

Cell-like compartments that spontaneously emerged from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Image created using confocal microscopy.

For more photos of cell-like compartments from frog eggs view: 6584, 6585, 6586, 6592, and 6593.

For videos of cell-like compartments from frog eggs view: 6587, 6588, 6589, and 6590.

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.

The image visualizes a part of the yeast molecular interaction network. The lines in the network represent connections among genes (shown as little dots) and different-colored networks indicate subnetworks, for instance, those in specific locations or pathways in the cell. Researchers use gene or protein expression data to build these networks; the network shown here was visualized with a program called Cytoscape. By following changes in the architectures of these networks in response to altered environmental conditions, scientists can home in on those genes that become central "hubs" (highly connected genes), for example, when a cell encounters stress. They can then further investigate the precise role of these genes to uncover how a cell's molecular machinery deals with stress or other factors. Related to images 3732 and 3733.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. This image shows how luciferase-based imaging could be used to visualize the heart for regeneration studies (left), or label all tissues for stem cell transplantation (right).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.

Time lapse series shows short dynamin assemblies (not visible) constricting a lipid tube to make a "beads on a string" appearance, then cutting off one of the beads i.e., catalyzing membrane fission). The lipids are fluorescent (artificially colored). Ramachandran R, Pucadyil T.J., Liu Y.W., Acharya S., Leonard M., Lukiyanchuk V., Schmid S.L. 2009. Membrane insertion of the pleckstrin homology domain variable loop 1 is critical for dynamin-catalyzed vesicle scission. Mol Biol Cell. 2009 20:4630-9.

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.

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.

NIGMS-funded researchers led by Roger Kornberg solved the structure of RNA polymerase II. This is the enzyme in mammalian cells that catalyzes the transcription of DNA into messenger RNA, the molecule that in turn dictates the order of amino acids in proteins. For his work on the mechanisms of mammalian transcription, Kornberg received the Nobel Prize in Chemistry in 2006.

Individual cells are color-coded based on their identity and signaling activity using a protein circuit technology developed by the Coyle Lab. Just as a radio allows you to listen to an individual frequency, this technology allows researchers to tune into the specific “radio station” of each cell through genetically encoded proteins from a bacterial system called MinDE. The proteins generate an oscillating fluorescent signal that transmits information about cell shape, state, and identity that can be decoded using digital signal processing tools originally designed for telecommunications. The approach allows researchers to look at the dynamics of a single cell in the presence of many other cells.

Related to video 7022.

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 neural crest cell-derived, migrating pigment cells in a salamander. 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, 5755, 5756 and 5757.

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. The image shows a side view of the structure of a protein composed of two smaller proteins, called E and M. Each E and M contributes two molecules to the overall protein structure (called a heterotetramer), which is important for assembling and holding together the viral membrane, i.e., the shell that surrounds the genetic material of the dengue virus. The dengue protein's structure has revealed some portions in the protein that might be good targets for developing medications that could be used to combat dengue virus infections. 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.

Staphylococcus aureus bacteria (green) grouping together upon contact with synovial fluid—a viscous substance found in joints. The formation of groups can help protect the bacteria from immune system defenses and from antibiotics, increasing the likelihood of an infection. This video is a 1-hour time lapse and was captured using a confocal laser scanning microscope.

More information about the research that produced this video can be found in the Journal of Bacteriology paper "In Vitro Staphylococcal Aggregate Morphology and Protection from Antibiotics Are Dependent on Distinct Mechanisms Arising from Postsurgical Joint Components and Fluid Motion" by Staats et al.

Related to images 6803 and 6804.

Telophase during mitosis: Nuclear membranes form around each of the two sets of chromosomes, the chromosomes begin to spread out, and the spindle begins to break down. Mitosis is responsible for growth and development, as well as for replacing injured or worn out cells throughout the body. For simplicity, mitosis is illustrated here with only six chromosomes.

Animation for the vesicular shuttle model of Golgi transport.

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.

This image shows a computer-generated, three-dimensional map of the rotavirus structure. This virus infects humans and other animals and causes severe diarrhea in infants and young children. By the age of five, almost every child in the world has been infected with this virus at least once. Scientists have found a vaccine against rotavirus, so in the United States there are very few fatalities, but in developing countries and in places where the vaccine is unavailable, this virus is responsible for more than 200,000 deaths each year.

The rotavirus comprises three layers: the outer, middle and inner layers. On infection, the outer layer is removed, leaving behind a "double-layered particle." Researchers have studied the structure of this double-layered particle with a transmission electron microscope. Many images of the virus at a magnification of ~50,000x were acquired, and computational analysis was used to combine the individual particle images into a three-dimensional reconstruction.

The image was rendered by Melody Campbell (PhD student at TSRI). Work that led to the 3D map was published in Campbell et al. Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure. 2012;20(11):1823-8. PMCID: PMC3510009.

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

The receptor is shown bound to an antagonist, JDTic.

Like a major city, a cell teems with specialized workers that carry out its daily operations--making energy, moving proteins, or helping with other tasks. Researchers took microscopic pictures of thin layers of a cell and then combined them to make this 3-D image featuring color-coded organelles--the cell's "workers." Using this image, scientists can understand how these specialized components fit together in the cell's packed inner world.

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.

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.

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

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."

In vivo vascular development in kdr:GFP frogs. Related to images 3403 and 3405.

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 video, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The video shows three key steps during the signaling process: phosphorylation of the T-cell receptor (green), 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 image 3787.

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.

A cell in prophase, near the start of mitosis: In the nucleus, chromosomes condense and become visible. In the cytoplasm, the spindle forms. Mitosis is responsible for growth and development, as well as for replacing injured or worn out cells throughout the body. For simplicity, mitosis is illustrated here with only six chromosomes.

The arrangement of identical molecular components can make a dramatic difference. For example, carbon atoms can be arranged into dull graphite (left) or sparkly diamonds (right). See image 2507 for an illustration with examples.

Dictyostelium discoideum is a microscopic amoeba. A group of 100,000 form a mound as big as a grain of sand. Featured in The New Genetics.

It's probably most people's least favorite activity, but we still need to do it--take out our trash. Otherwise our homes will get cluttered and smelly, and eventually, we'll get sick. The same is true for our cells: garbage disposal is an ongoing and essential activity, and our cells have a dedicated waste-management system that helps keep them clean and neat. One major waste-removal agent in the cell is the lysosome. Lysosomes are small structures, called organelles, and help the body to dispose of proteins and other molecules that have become damaged or worn out.

This image shows a massive accumulation of lysosomes (visualized with LAMP1 immunofluorescence, in purple) within nerve cells that surround amyloid plaques (visualized with beta-amyloid immunofluorescence, in light blue) in a mouse model of Alzheimer's disease. Scientists have linked accumulation of lysosomes around amyloid plaques to impaired waste disposal in nerve cells, ultimately resulting in cell death.

Mitochondria are the powerhouses of the cells, generating the energy the cells need to do their tasks and to stay alive. Researchers have studied mitochondria for some time because when these cell organelles don't work as well as they should, several diseases develop. In this photograph of cow cells taken with a microscope, the mitochondria were stained in bright yellow to visualize them in the cell. The large blue dots are the cell nuclei and the gray web is the cytoskeleton of the cells.

Animation for the cisternae maturation model of Golgi transport.

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.

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.

Sulfite oxidase is an enzyme that is essential for normal neurological development in children. This video shows the active site of the enzyme and its molybdenum cofactor visible as a faint ball-and-stick representation buried within the protein. The positively charged channel (blue) at the active site contains a chloride ion (green) and three water molecules (red). As the protein oscillates, one can see directly down the positively charged channel. At the bottom is the molybdenum atom of the active site (light blue) and its oxo group (red) that is transferred to sulfite to form sulfate in the catalytic reaction.

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).

About half of all human proteins include chains of sugar molecules that are critical for the proteins to function properly. Appears in the NIGMS booklet Inside the Cell.

A colorized scanning electron micrograph of bacteria. Scanning electron microscopes allow scientists to see the three-dimensional surface of their samples.

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.