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.

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

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.

If a picture is worth a thousand words, what's a movie worth? For researchers studying cell migration, a "documentary" of fruit fly cells (bright green) traversing an egg chamber could answer longstanding questions about cell movement. Historically, researchers have been unable to watch this cell migration unfold in living ovarian tissue in real time. But by developing a culture medium that allows fly eggs to survive outside their ovarian homes, scientists can observe the nuances of cell migration as it happens. Such details may shed light on how immune cells move to a wound and why cancer cells spread to other sites. See 3594 for still image.

Drugs enter different layers of skin via intramuscular, subcutaneous, or transdermal delivery methods. See image 2532 for a labeled version of this illustration. Featured in Medicines By Design.

Myelinated axons in a rat spinal root. Myelin is a type of fat that forms a sheath around and thus insulates the axon to protect it from losing the electrical current needed to transmit signals along the axon. The axoplasm inside the axon is shown in pink. Related to 3397.

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 in the fin of pearl danio, a close relative of the popular laboratory animal zebrafish. 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 5758.

This image shows the hierarchical ontology of genes, cellular components and processes derived from large genomic datasets. From Dutkowski et al. A gene ontology inferred from molecular networks Nat Biotechnol. 2013 Jan;31(1):38-45. Related to 3437.

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.

Skins cells were reprogrammed into heart muscle cells. The cells highlighted in green are remaining skin cells. Red indicates a protein that is unique to heart muscle. The technique used to reprogram the skin cells into heart cells could one day be used to mend heart muscle damaged by disease or heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Ribosomes manufacture proteins based on mRNA instructions. Each ribosome reads mRNA, recruits tRNA molecules to fetch amino acids, and assembles the amino acids in the proper order.

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 3428.

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.

When a molecule arrives at a cell's outer membrane, the membrane creates a pouch around the molecule that protrudes inward. Directed by a protein called dynamin, the pouch then gets pinched off to form a vesicle that carries the molecule to the right place inside the cell. To better understand how dynamin performs its vital pouch-pinching role, researchers determined its structure. Based on the structure, they proposed that a dynamin "collar" at the pouch's base twists ever tighter until the vesicle pops free. Because cells absorb many drugs through vesicles, the discovery could lead to new drug delivery methods.

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.

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

The HIV capsid is a pear-shaped structure that is made of proteins the virus needs to mature and become infective. The capsid is inside the virus and delivers the virus' genetic information into a human cell. To better understand how the HIV capsid does this feat, scientists have used computer programs to simulate its assembly. This image shows a series of snapshots of the steps that grow the HIV capsid. A model of a complete capsid is shown on the far right of the image for comparison; the green, blue and red colors indicate different configurations of the capsid protein that make up the capsid “shell.” The bar in the left corner represents a length of 20 nanometers, which is less than a tenth the size of the smallest bacterium. Computer models like this also may be used to reconstruct the assembly of the capsids of other important viruses, such as Ebola or the Zika virus. The studies reporting this research were published in Nature Communications and Nature. To learn more about how researchers used computer simulations to track the assembly of the HIV capsid, see this press release from the University of Chicago.

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

For more photos of cell-like compartments from frog eggs view: 6584, 6585, 6586, 6591, 6592, and 6593.

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

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.

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

The proteasome is a critical multiprotein complex in the cell that breaks down and recycles proteins that have become damaged or are no longer needed. This movie shows how a protein substrate (red) is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region then gets engaged by the AAA+ motor of the proteasome (cyan), which initiates mechanical pulling, unfolding and movement of the protein into the proteasome's interior for cleavage into shorter protein pieces called peptides. During movement of the substrate, its ubiquitin modification gets cleaved off by the deubiquitinase Rpn11 (green), which sits directly above the entrance to the AAA+ motor pore and acts as a gatekeeper to ensure efficient ubiquitin removal, a prerequisite for fast protein breakdown by the 26S proteasome. Related to image 3763.

Like a map showing heavily traveled roads, this mathematical model of metabolic activity inside an E. coli cell shows the busiest pathway in white. Reaction pathways used less frequently by the cell are marked in red (moderate activity) and green (even less activity). Visualizations like this one may help scientists identify drug targets that block key metabolic pathways in bacteria.

Undifferentiated embryonic stem cells cease to exist a few days after conception. In this image, ES cells are shown to differentiate into sperm, muscle fiber, hair cells, nerve cells, and cone cells.

Microfluidic chips have many uses in biology labs. The one shown here was used by bioengineers to study bacteria, allowing the researchers to synchronize their fluorescing so they would blink in unison. Related to images 3266 and 3268. From a UC San Diego news release, "Researchers create living 'neon signs' composed of millions of glowing bacteria."

Top view of myelinated axons in a rat spinal root. Myelin is a type of fat that forms a sheath around and thus insulates the axon to protect it from losing the electrical current needed to transmit signals along the axon. The axoplasm inside the axon is shown in pink. Related to 3396.

X-ray crystallography allows researchers to see structures too small to be seen by even the most powerful microscopes. To visualize the arrangement of atoms within molecules, researchers can use the diffraction patterns obtained by passing X-ray beams through crystals of the molecule. This is a common way for solving the structures of proteins. See image 2512 for a labeled version of this illustration. Featured in The Structures of Life.

Hydra magnipapillata is an invertebrate animal used as a model organism to study developmental questions, for example the formation of the body axis.

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.

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 2551 for a labeled version of this illustration. Featured in The New Genetics.

Details about the basic biology and chemistry of the ingredients that produce bioluminescence are allowing scientists to harness it as an imaging tool. Credit: Nathan Shaner, Scintillon Institute.

From Biomedical Beat article July 2017: Chasing Fireflies—and Better Cellular Imaging Techniques

A protein called kinesin (blue) is in charge of moving cargo around inside cells and helping them divide. It's powered by biological fuel called ATP (bright yellow) as it scoots along tube-like cellular tracks called microtubules (gray).

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.

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.

Along with blood vessels (red) and nerve cells (green), this mouse brain shows abnormal protein clumps known as plaques (blue). These plaques multiply in the brains of people with Alzheimer's disease and are associated with the memory impairment characteristic of the disease. Because mice have genomes nearly identical to our own, they are used to study both the genetic and environmental factors that trigger Alzheimer's disease. Experimental treatments are also tested in mice to identify the best potential therapies for human patients.

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

These mitochondria (red) are from the heart muscle cell of a rat. Mitochondria have an inner membrane that folds in many places (and that appears here as striations). This folding vastly increases the surface area for energy production. Nearly all our cells have mitochondria. Related to image 3664.

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.

This image of human red blood cells was obtained with the help of a scanning electron microscope, an instrument that uses a finely focused electron beam to yield detailed images of the surface of a sample.

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.

These smooth muscle cells were derived from human embryonic stem cells. The nuclei are stained blue, and the proteins of the cytoskeleton are stained green. Image and caption information courtesy of the California Institute for Regenerative Medicine.

The human body keeps time with a master clock called the suprachiasmatic nucleus or SCN. Situated inside the brain, it's a tiny sliver of tissue about the size of a grain of rice, located behind the eyes. It sits quite close to the optic nerve, which controls vision, and this means that the SCN "clock" can keep track of day and night. The SCN helps control sleep and maintains our circadian rhythm--the regular, 24-hour (or so) cycle of ups and downs in our bodily processes such as hormone levels, blood pressure, and sleepiness. The SCN regulates our circadian rhythm by coordinating the actions of billions of miniature "clocks" throughout the body. These aren't actually clocks, but rather are ensembles of genes inside clusters of cells that switch on and off in a regular, 24-hour (or so) cycle in our physiological day.

Influenza (flu) virus proteins in the act of self-replication. Viral nucleoprotein (blue) encapsidates [encapsulates] the RNA genome (green). The influenza virus polymerase (orange) reads and copies the RNA genome. In the background is an image of influenza virus ribonucleoprotein complexes observed using cryo-electron microscopy. This image is from a November 2012 News Release.

A growing Vibrio cholerae (cholera) biofilm. Cholera bacteria form colonies called biofilms that enable them to resist antibiotic therapy within the body and other challenges to their growth.

Each slightly curved comma shape represents an individual bacterium from assembled confocal microscopy images. Different colors show each bacterium’s position in the biofilm in relation to the surface on which the film is growing.

Related to image 6355.

This image shows the hierarchical ontology of genes, cellular components and processes derived from large genomic datasets. From Dutkowski et al. A gene ontology inferred from molecular networks Nat Biotechnol. 2013 Jan;31(1):38-45. Related to 3436.

A sensor particle being engulfed by a macrophage—an immune cell—and encapsuled in a compartment called a phagosome. The phagosome then fuses with lysosomes—another type of compartment. The left video shows snowman-shaped sensor particles with fluorescent green nanoparticle “heads” and “bodies” colored red by Förster Resonance Energy Transfer (FRET)-donor fluorophores. The middle video visualizes light blue FRET signals that are only generated when the “snowman” sensor—the FRET-donor—fuses with the lysosomes, which are loaded with FRET-acceptors. The right video combines the other two. The videos were captured using epi-fluorescence microscopy.

More details can be found in the paper “Transport motility of phagosomes on actin and microtubules regulates timing and kinetics of their maturation” by Yu et al.

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

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

Relapsing fever is caused by a bacterium and transmitted by certain soft-bodied ticks or body lice. The disease is seldom fatal in humans, but it can be very serious and prolonged. This scanning electron micrograph shows Borrelia hermsii (green), one of the bacterial species that causes the disease, interacting with red blood cells. Micrograph by Robert Fischer, NIAID.

For more information on this see, relapsing fever.

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

Floral pattern emerging as two bacterial species, motile Acinetobacter baylyi and non-motile Escherichia coli (green), are grown together for 24 hours on 0.75% agar surface from a small inoculum in the center of a Petri dish.

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 6556 for a photo of this process at 72 hours on 0.5% agar surface.
See 6550 for a video of this process.

During development, a zebrafish embryo is transformed from a ball of cells into a recognizable body plan by sweeping convergence and extension cell movements. This process is called gastrulation. Each line in this video represents the movement of a single zebrafish embryo cell over the course of 3 hours. The video was created using time-lapse confocal microscopy. Related to image 6775.