The fly fatbody is a nutrient storage and mobilization organ akin to the mammalian liver. The engulfment receptor Draper (green) is located at the cell surface of fatbody cells. The cell nuclei are shown in blue.

Histone proteins loop together with double-stranded DNA to form a structure that resembles beads on a string. See image 2560 for an unlabeled version of this illustration. Featured in The New Genetics.

The extracellular matrix (ECM) is most prevalent in connective tissues but also is present between the stems (axons) of nerve cells, as shown here. Blue-colored nerve cell axons are surrounded by brown-colored, myelin-supplying Schwann cells, which act like insulation around an electrical wire to help speed the transmission of electric nerve impulses down the axon. The ECM is pale pink. The tiny brown spots within it are the collagen fibers that are part of the ECM.

Cell-like compartments that spontaneously emerged from scrambled frog eggs. Endoplasmic reticulum (red) and microtubules (green) are visible. Image created using epifluorescence microscopy.

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

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

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.

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.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3414, 3415, 3416, 3417, 3418, and 3419.

Scientists revealed a detailed image of the genetic defect that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease.

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.

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 2506 for an illustration without examples.

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 2514 and 2515 for labeled versions of this illustration. Featured in The Structures of Life.

The fledgling field of X-ray microscopy lets researchers look inside whole cells rapidly frozen to capture their actions at that very moment. Here, a yeast cell buds before dividing into two. Colors show different parts of the cell. Seeing whole cells frozen in time will help scientists observe cells' complex structures and follow how molecules move inside them.

The three neurons (red) visible in this image were derived from human embryonic stem cells. Undifferentiated stem cells are green here. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Groups of Staphylococcus aureus bacteria (blue) attached to a microstructured titanium surface (green) that mimics an orthopedic implant used in joint replacement. The attachment of pre-formed groups of bacteria may lead to infections because the groups can tolerate antibiotics and evade the immune system. This image was captured using a scanning electron microscope.

More information on the research that produced this image can be found in the Antibiotics paper "Free-floating aggregate and single-cell-initiated biofilms of Staphylococcus aureus" by Gupta et al.

Related to image 6804 and video 6805.

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.

A crane fly spermatocyte during metaphase of meiosis-I, a step in the production of sperm. A meiotic spindle pulls apart three pairs of autosomal chromosomes, along with a sex chromosome on the right. Tubular mitochondria surround the spindle and chromosomes. This video was captured with quantitative orientation-independent differential interference contrast and is a time lapse showing a 1-second image taken every 30 seconds over the course of 30 minutes.

More information about the research that produced this video can be found in the J. Biomed Opt. paper “Orientation-Independent Differential Interference Contrast (DIC) Microscopy and Its Combination with Orientation-Independent Polarization System” by Shribak et. al.

Superresolution microscopy work on endoplasmic reticulum (ER) in the peripheral areas of the cell showing details of the structure and arrangement in a complex web of tubes.
The ER is a continuous membrane that extends like a net from the envelope of the nucleus outward to the cell membrane. The ER plays several roles within the cell, such as in protein and lipid synthesis and transport of materials between organelles. The ER has a flexible structure to allow it to accomplish these tasks by changing shape as conditions in the cell change. Shown here an image created by super-resolution microscopy of the ER in the peripheral areas of the cell showing details of the structure and the arrangements in a complex web of tubes. Related to images 5856 and 5857.

Solution NMR structure of protein target WR41 (left) from C. elegans. Noting the unanticipated structural similarity to the ubiquitin protein (Ub) found in all eukaryotic cells, researchers discovered that WR41 is a Ub-like modifier, ubiquitin-fold modifier 1 (Ufm1), on a newly uncovered ubiquitin-like pathway. Subsequently, the PSI group also determined the three-dimensional structure of protein target HR41 (right) from humans, the E2 ligase for Ufm1, using both NMR and X-ray crystallography.

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. See more information in the article in Science.

Related to images 3497 and 3498.

Actin is an essential protein in a cell's skeleton (cytoskeleton). It forms a dense network of thin filaments in the cell. Here, researchers have used a technique called stochastic optical reconstruction microscopy (STORM) to visualize the actin network in a cell in three dimensions. The actin strands were labeled with a dye called Alexa Fluor 647-phalloidin.  This image appears in a study published by Nature Methods, which reports how researchers use STORM to visualize the cytoskeleton.

Scientists have long known that multicellular organisms use biological molecules produced by one cell and sensed by another to transmit messages that, for instance, guide proper development of organs and tissues. But it's been a puzzle as to how molecules dumped out into the fluid-filled spaces between cells can precisely home in on their targets. Using living tissue from fruit flies, a team led by Thomas Kornberg of the University of California, San Francisco, has shown that typical cells in animals can talk to each other via long, thin cell extensions called cytonemes (Latin for "cell threads") that may span the length of 50 or 100 cells. The point of contact between a cytoneme and its target cell acts as a communications bridge between the two cells.

This photograph shows a panoramic view of HeLa cells, a cell line many researchers use to study a large variety of important research questions. The cells' nuclei containing the DNA are stained in blue and the cells' cytoskeletons in gray.

Two fruit fly (Drosophila melanogaster) larvae brains with neurons expressing fluorescently tagged tubulin protein. Tubulin makes up strong, hollow fibers called microtubules that play important roles in neuron growth and migration during brain development. This image was captured using confocal microscopy, and the color indicates the position of the neurons within the brain.

Kinases are enzymes that add phosphate groups (red-yellow structures) to proteins (green), assigning the proteins a code. In this reaction, an intermediate molecule called ATP (adenosine triphosphate) donates a phosphate group from itself, becoming ADP (adenosine diphosphate). See image 2534 for an unlabeled version of this illustration. Featured in Medicines By Design.

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

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

The glial cells (black dots) and nerve cells (brown bands) in this developing fruit fly nerve cord formed normally despite the absence of the SPITZ protein, which blocks their impending suicide. The HID protein, which triggers suicide, is also lacking in this embryo.

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.

Living primary mouse embryonic fibroblasts. Mitochondria (green) stained with the mitochondrial membrane potential indicator, rhodamine 123. Nuclei (blue) are stained with DAPI. Caption from a November 26, 2012 news release from U Penn (Penn Medicine).

Serum albumin (SA) is the most abundant protein in the blood plasma of mammals. SA has a characteristic heart-shape structure and is a highly versatile protein. It helps maintain normal water levels in our tissues and carries almost half of all calcium ions in human blood. SA also transports some hormones, nutrients and metals throughout the bloodstream. Despite being very similar to our own SA, those from other animals can cause some mild allergies in people. Therefore, some scientists study SAs from humans and other mammals to learn more about what subtle structural or other differences cause immune responses in the body.

Related to entries 3744 and 3746

Normal mice, like the B6 breed pictured on the left, develop scars when their ears are pierced. The Murphy Roths Large (MRL) mice pictured on the right can grow back lost ear tissue thanks to an inactive version of the p21 gene. When researchers knocked out that same gene in other mouse breeds, their ears also healed completely without scarring. Journal Article: Clark, L.D., Clark, R.K. and Heber-Katz, E. 1998. A new murine model for mammalian wound repair and regeneration. Clin Immunol Immunopathol 88: 35-45.

Cancer cells can change their migration phenotype, which includes their shape and the way that they move to invade different tissues. This movie shows breast cancer cells forming a tumor spheroid—a 3D ball of cancer cells—and invading the surrounding tissue. Images were taken using a laser scanning confocal microscope, and artificial intelligence (AI) models were used to segment and classify the images by migration phenotype. On the right side of the video, each phenotype is represented by a different color, as recognized by the AI program based on identifiable characteristics of those phenotypes. The movie demonstrates how cancer cells can use different migration modes during growth and metastasis—the spreading of cancer cells within the body.

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.

Two models for how material passes through the Golgi apparatus: the vesicular shuttle model and the cisternae maturation model.

DNA doesn't leave a fossil record in stone, the way bones do. Instead, the DNA code itself holds the best evidence for organisms' genetic history. Some of the most telling evidence about genetic history comes from retroviruses, the remnants of ancient viral infections.

This image captures Purkinje cells (red), one of the main types of nerve cell found in the brain. These cells have elaborate branching structures called dendrites that receive signals from other nerve cells.

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

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.

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

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.

Anaphase is the critical step during mitosis when sister chromosomes are disjoined and directed to opposite spindle poles, ensuring equal distribution of the genome during cell division. In this image, one pair of sister chromosomes at the top was lost and failed to divide after chemical inhibition of polo-like kinase 1. This image depicts chromosomes (blue) separating away from the spindle mid-zone (red). Kinetochores (green) highlight impaired movement of some chromosomes away from the mid-zone or the failure of sister chromatid separation (top). Scientists are interested in detailing the signaling events that are disrupted to produce this effect. The image is a volume projection of multiple deconvolved z-planes acquired with a Nikon widefield fluorescence microscope.

This image was chosen as a winner of the 2016 NIH-funded research image call. The research that led to this image was funded by NIGMS.

Related to image 5765.

Like a world of its own, this sphere represents all the known chemical reactions in the E. coli bacterium. The colorful circles on the surface symbolize sets of densely interconnected reactions. The lines between the circles show additional connecting reactions. The shapes inside the circles are landmark molecules, like capital cities on a map, that either act as hubs for many groups of reactions, are highly conserved among species, or both. Molecules that connect far-flung reactions on the sphere are much more conserved during evolution than molecules that connect reactions within a single circle. This statistical cartography could reveal insights about other complex systems, such as protein interactions and gene regulation networks.

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.

Kinases are enzymes that add phosphate groups (red-yellow structures) to proteins (green), assigning the proteins a code. In this reaction, an intermediate molecule called ATP (adenosine triphosphate) donates a phosphate group from itself, becoming ADP (adenosine diphosphate). See image 2535 for a labeled version of this illustration. Featured in Medicines By Design.

From PDB entry 3c6k, Crystal structure of human spermine synthase in complex with spermidine and 5-methylthioadenosine.

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 difference in how the proteins in each compartment mix with water and with each other. These differences let them 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 3791, image 3792 and image 3793.

Gene transcription is a process by which the genetic information encoded in DNA is transcribed into RNA. It's essential for all life and requires the activity of proteins, called transcription factors, that detect where in a DNA strand transcription should start. In eukaryotes (i.e., those that have a nucleus and mitochondria), a protein complex comprising 14 different proteins is responsible for sniffing out transcription start sites and starting the process. This complex, called TFIID, represents the core machinery to which an enzyme, named RNA polymerase, can bind to and read the DNA and transcribe it to RNA. Scientists have used cryo-electron microscopy (cryo-EM) to visualize the TFIID-RNA polymerase-DNA complex in unprecedented detail. In this illustration, TFIID (blue) contacts the DNA and recruits the RNA polymerase (gray) for gene transcription. The start of the transcribed gene is shown with a flash of light. To learn more about the research that has shed new light on gene transcription, see this news release from Berkeley Lab. Related to video 5730.

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Cells are connected to one another by their cell walls, shown in blue. Stained cytoplasm (green) and membranes (magenta) show that the individual cells remain separate. This image was captured using spinning disk confocal microscopy.

Related to images 6969 and 6971.

This image of the hippocampus was taken with an ultra-widefield high-speed multiphoton laser microscope. Tissue was stained to reveal the organization of glial cells (cyan), neurofilaments (green) and DNA (yellow). The microscope Deerinck used was developed in conjunction with Roger Tsien (2008 Nobel laureate in Chemistry) and remains a powerful and unique tool today.

Of the three muscle fibers shown here, the one on the right and the one on the left are normal. The middle fiber is deficient a large protein called nebulin (blue). Nebulin plays a number of roles in the structure and function of muscles, and its absence is associated with certain neuromuscular 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 fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.