Cells keep time to know when to retire.

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.

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.

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

The nucleolus is a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from differences in how the proteins in each compartment mix with water and with each other. These differences let the proteins readily separate from each other into the three nucleolus compartments.

This video of nucleoli in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows how each of the compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue) spontaneously fuse with each other on encounter without mixing with the other compartments.

For more details on this research, see this press release from Princeton. Related to video 3789, image 3792 and image 3793.

An atomic force microscopy image shows DNA folded into an intricate, computer-designed structure. The image is featured on Biomedical Beat blog post Cool Images: A Holiday-Themed Collection. For more background on DNA origami, see Cool Image: DNA Origami. See also related image 3690.

Multiphoton fluorescence image of HeLa cells stained with the actin binding toxin phalloidin (red), microtubules (cyan) and cell nuclei (blue). Nikon RTS2000MP custom laser scanning microscope. See related images 3518, 3519, 3520, 3522.

An NMR solution structure model of the transfer RNA splicing enzyme endonuclease in humans (subunit Sen15). This represents the first structure of a eukaryotic tRNA splicing endonuclease subunit.

Glial cells (stained green) in a fruit fly developing embryo have survived thanks to a signaling pathway initiated by neighboring nerve cells (stained red).

A cropped image of a white poppy. View poppy uncropped here 3424.

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

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

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

Ecteinascidin 743 (ET-743, brand name Yondelis), was discovered and isolated from a sea squirt, Ecteinascidia turbinata, by NIGMS grantee Kenneth Rinehart at the University of Illinois. It was synthesized by NIGMS grantees E.J. Corey and later by Samuel Danishefsky. Multiple versions of this structure are available as entries 2790-2797.

For fruit flies, the salivary gland is used to secrete materials for making the pupal case, the protective enclosure in which a larva transforms into an adult fly. For scientists, this gland provided one of the earliest glimpses into the genetic differences between individuals within a species. Chromosomes in the cells of these salivary glands replicate thousands of times without dividing, becoming so huge that scientists can easily view them under a microscope and see differences in genetic content between individuals.

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

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. Featured in the March 2006, issue of Findings in "Viral Voyages."

Image of Streptococcus, a type (genus) of spherical bacteria that can colonize the throat and back of the mouth. Stroptococci often occur in pairs or in chains, as shown 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 2570 and 2571.

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.

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.

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 stereo microscope.

Related to images 6927 and 6928.

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.

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.

Bioengineers were able to coax bacteria to blink in unison on microfluidic chips. This image shows a small chip with about 500 blinking bacterial colonies or biopixels. Related to images 3265 and 3268. From a UC San Diego news release, "Researchers create living 'neon signs' composed of millions of glowing bacteria."

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 and have lined up in the middle of the dividing cell.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1018, 1019, and 1021.

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 5883. NIH Director Francis Collins featured this on his blog on January 14, 2016.

At the root tips of the mustard plant Arabidopsis thaliana (red), two proteins work together to control the uptake of water and nutrients. When the cell division-promoting protein called Short-root moves from the center of the tip outward, it triggers the production of another protein (green) that confines Short-root to the nutrient-filtering endodermis. The mechanism sheds light on how genes and proteins interact in a model organism and also could inform the engineering of plants.

Confocal image showing high levels of the protein vimentin (white) at the edge zone of a quail embryo. Cell nuclei are labeled green. More specifically, this high-magnification (60X) image shows vimentin immunofluorescence in the edge zone (top of image) and inner zone (bottom of image) of a Stage 4 quail blastoderm. Vimentin expression (white) is shown merged with Sytox nuclear labeling (green) at the edge of the blastoderm. A thick vimentin filament runs circumferentially (parallel to the direction of the edge) that appears to delineate the transition between the edge zone and interior zone. Also shown are dense vimentin clusters or foci, which typically appear to be closely associated with edge cell nuclei. An NIGMS grant to Professor Garcia was used to purchase the confocal microscope that collected this image. Related to image 2808 and video 2809.

Hepatocytes, like the one shown here, are the most abundant type of cell in the human liver. They play an important role in building proteins; producing bile, a liquid that aids in digesting fats; and chemically processing molecules found normally in the body, like hormones, as well as foreign substances like medicines and alcohol.

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

This time-lapse movie shows that bacterial communities called biofilms can create blockages that prevent fluid flow in devices such as stents and catheters over a period of about 56 hours. This video was featured in a news release from Princeton University.

This ACAPELLA robot for capillary protein crystallization grows protein crystals, freezes them, and centers them without manual intervention. The close-up is a view of one of the dispensers used for dispensing proteins and reagents.

This fused chromosome has two functional centromeres, shown as two sets of red and green dots. Centromeres are DNA/protein complexes that are key to splitting the chromosomes evenly during cell division. When dicentric chromosomes like this one are formed in a person, fertility problems or other difficulties may arise. Normal chromosomes carrying a single centromere (one set of red and green dots) are also visible in this image.

On the left, a cross-section slice of a rat pancreas cell captured using cryo-electron tomography (cryo-ET). On the right, a 3D, color-coded version of the image highlighting cell structures. Visible features include the folded sacs of the Golgi apparatus (copper), transport vesicles (medium-sized dark-blue circles), microtubules (neon green), ribosomes (small pale-yellow circles), and lysosomes (large yellowish-green circles). Black line (bottom right of the left image) represents 200 nm. This image is a still from video 6609.

DNA consists of two long, twisted chains made up of nucleotides. Each nucleotide contains one base, one phosphate molecule, and the sugar molecule deoxyribose. The bases in DNA nucleotides are adenine, thymine, cytosine, and guanine. See image 2542 for a labeled version of this illustration. Featured in The New Genetics.

Enzymes speed up chemical reactions by reducing the amount of energy needed for the reactions. The substrate (lactose) binds to the active site of the enzyme (lactase) and is converted into products (sugars).

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.

Collecting and transporting cellular waste and sorting it into recylable and nonrecylable pieces is a complex business in the cell. One key player in that process is the endosome, which helps collect, sort and transport worn-out or leftover proteins with the help of a protein assembly called the endosomal sorting complexes for transport (or ESCRT for short). These complexes help package proteins marked for breakdown into intralumenal vesicles, which, in turn, are enclosed in multivesicular bodies for transport to the places where the proteins are recycled or dumped. In this image, two multivesicular bodies (with yellow membranes) contain tiny intralumenal vesicles (with a diameter of only 25 nanometers; shown in red) adjacent to the cell's vacuole (in orange).

Scientists working with baker's yeast (Saccharomyces cerevisiae) study the budding inward of the limiting membrane (green lines on top of the yellow lines) into the intralumenal vesicles. This tomogram was shot with a Tecnai F-20 high-energy electron microscope, at 29,000x magnification, with a 0.7-nm pixel, ~4-nm resolution.

To learn more about endosomes, see the Biomedical Beat blog post The Cell’s Mailroom. Related to a microscopy photograph 5768 that was used to generate this illustration and a zoomed-in version 5767 of this illustration.

Many of today's medicines come from products found in nature, such as this sponge found off the coast of Palau in the Pacific Ocean. Chemists have synthesized a compound called Palau'amine, which appears to act against cancer, bacteria and fungi. In doing so, they invented a new chemical technique that will empower the synthesis of other challenging molecules.

The three fibers of the cytoskeleton--microtubules in blue, intermediate filaments in red, and actin in green--play countless roles in the cell.

Various views of a zebrafish head with blood vessels shown in purple. Researchers often study zebrafish because they share many genes with humans, grow and reproduce quickly, and have see-through eggs and embryos, which make it easy to study early stages of development.

This video was captured using a light sheet microscope.

Related to image 6934.

Drosophila adult brain showing that an adipokine (fat hormone) generates a response from neurons (aqua) and regulates insulin-producing neurons (red).

Related to images 6982, 6983, and 6984.

Planarians are freshwater flatworms that have powerful abilities to regenerate their bodies, which would seem to make them natural model organisms in which to study stem cells. But until recently, scientists had not been able to efficiently find the genes that regulate the planarian stem cell system. In this image, a single stem cell has given rise to a colony of stem cells in a planarian. Proliferating cells are red, and differentiating cells are blue. Quantitatively measuring the size and ratios of these two cell types provides a powerful framework for studying the roles of stem cell regulatory genes in planarians.

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. 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.

This image capture shows how a single gene, STM, plays a starring role in plant development. This gene acts like a molecular fountain of youth, keeping cells ever-young until it’s time to grow up and commit to making flowers and other plant parts. Because of its ease of use and low cost, Arabidopsis is a favorite model for scientists to learn the basic principles driving tissue growth and regrowth for humans as well as the beautiful plants outside your window. Image captured from video Watch Flowers Spring to Life, featured in the NIH Director's Blog: Watch Flowers Spring to Life.

A computer model of the cell membrane, where the plasma membrane is red, endoplasmic reticulum is yellow, and mitochondria are blue. This image relates to a July 27, 2009 article in Computing Life.

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.

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 (dark oval shapes) invaded the worm’s gut cells (long tube; the cell nuclei are shown in red) 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 5779.

A cross section of the measles virus in which six proteins (enlarged on the outside of the virus) work together to infect cells. The measles virus is extremely infectious; 9 out of 10 people exposed will contract the disease. Fortunately, an effective vaccine protects against infection. Portions of the proteins that have not been determined are shown with dots.

Learn more about the six proteins on PDB 101’s Molecule of the Month: Measles Virus Proteins. Structures are available for the ordered regions of nucleoprotein and phosphoprotein (PDB entries 5E4V, 3ZDO, 1T6O), but the remaining regions are thought to form a flexible, random tangle. For a larger look at the measles virus, see 6995.

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

Some children are born with a mutation in a regulatory site on this enzyme that causes them to over-secrete insulin when they consume protein. We found that a compound from green tea (shown in the stick figure and by the yellow spheres on the enzyme) is able to block this hyperactivity when given to animals with this disorder.