Three fruit fly (Drosophila melanogaster) ovarioles (yellow, blue, and magenta) with egg cells visible inside them. Ovarioles are tubes in the reproductive systems of female insects. Egg cells form at one end of an ovariole and complete their development as they reach the other end, as shown in the yellow wild-type ovariole. This process requires an important protein that is missing in the blue and magenta ovarioles. This image was created using confocal microscopy.

More information on the research that produced this image can be found in the Current Biology paper “Gatekeeper function for Short stop at the ring canals of the Drosophila ovary” by Lu et al.

To simulate the consequences of disrupting bacterial cell-to-cell communication, called quorum sensing, in the crypts (small chambers within the colon), the researchers experimented with an inhibitor molecule (i.e., antagonist) to turn off quorum sensing in methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant strain of bacteria that often causes human infections. In this experiment, a medium promoting bacterial growth flows through experimental chambers mimicking the colon environment. The chambers on the right contained no antagonist. In the left chambers, after being added to the flowing medium, the quorum-sensing-inhibiting molecules quickly spread throughout the crevices, inactivating quorum sensing and reducing colonization. These results suggest a potential strategy for addressing MRSA virulence via inhibitors of bacterial communication. You can read more about this research here.

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. Image created using confocal microscopy.

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

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

Melanoma (skin cancer) cells undergoing programmed cell death, also called apoptosis. This process was triggered by raising the pH of the medium that the cells were growing in. Melanoma in people cannot be treated by raising pH because that would also kill healthy cells. This video was taken using a differential interference contrast (DIC) microscope.

Cells keep time to know when to retire.

Stained glomeruli in the kidney. The kidney is an essential organ responsible for disposing wastes from the body and for maintaining healthy ion levels in the blood. It works like a purifier by pulling break-down products of metabolism, such as urea and ammonium, from the bloodstream for excretion in urine. The glomerulus is a structure that helps filter the waste compounds from the blood. It consists of a network of capillaries enclosed within a Bowman's capsule of a nephron, which is the structure in which ions exit or re-enter the blood in the kidney.

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.

Cryo-electron microscopy (cryo-EM) has the power to capture details of proteins and other small biological structures at the molecular level.  This image shows proteins in the capsid, or outer cover, of bacteriophage P22, a virus that infects the Salmonella bacteria. Each color shows the structure and position of an individual protein in the capsid. Thousands of cryo-EM scans capture the structure and shape of all the individual proteins in the capsid and their position relative to other proteins. A computer model combines these scans into the three-dimension image shown here. Related to image 5875.

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 photograph shows a magnified view of a Drosophila melanogaster pupa in cross section. Compare this normal pupa to one that lacks an important receptor, shown in image 2759.

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.

This image captures the many layers of nerve cells in the retina. The top layer (green) is made up of cells called photoreceptors that convert light into electrical signals to relay to the brain. The two best-known types of photoreceptor cells are rod- and cone-shaped. Rods help us see under low-light conditions but can't help us distinguish colors. Cones don't function well in the dark but allow us to see vibrant colors in daylight.

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

Detail of a subunit of the capsid, or outer cover, of bacteriophage P22, a virus that infects the Salmonella bacteria. Cryo-electron microscopy (cryo-EM) was used to capture details of the capsid proteins, each shown here in a separate color. Thousands of cryo-EM scans capture the structure and shape of all the individual proteins in the capsid and their position relative to other proteins. A computer model combines these scans into the image shown here. Related to image 5874.

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.

Leptospira, shown here in green, is a type (genus) of elongated, spiral-shaped bacteria. Infection can cause Weil's disease, a kind of jaundice, in humans.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. In this image, a cardiac muscle-restricted promoter drives firefly luciferase expression.
For imagery of both the lateral and overhead view go to 3556.
For imagery of the lateral view go to 3558.
For more information about the illumated area go to 3559.

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.

The cytoskeleton (green) and DNA (purple) are highlighed in these cells by immunofluorescence.

In this image, recombinant probes known as FingRs (Fibronectin Intrabodies Generated by mRNA display) were expressed in a cortical neuron, where they attached fluorescent proteins to either PSD95 (green) or Gephyrin (red). PSD-95 is a marker for synaptic strength at excitatory postsynaptic sites, and Gephyrin plays a similar role at inhibitory postsynaptic sites. Thus, using FingRs it is possible to obtain a map of synaptic connections onto a particular neuron in a living cell in real time.

An Arachnoidiscus diatom with a diameter of 190µm. Diatoms are microscopic algae that have cell walls made of silica, which is the strongest known biological material relative to its density. In Arachnoidiscus, the cell wall is a radially symmetric pillbox-like shell composed of overlapping halves that contain intricate and delicate patterns. Sometimes, Arachnoidiscus is called “a wheel of glass.”

This image was taken with the orientation-independent differential interference contrast microscope.

Many disease-causing microbes manipulate their host’s metabolism and cells for their own ends. Microsporidia—which are parasites closely related to fungi—infect and multiply inside animal cells, and take the rearranging of cells’ interiors to a new level. They reprogram animal cells such that the cells start to fuse, causing them to form long, continuous tubes. As shown in this image of the roundworm Caenorhabditis elegans, microsporidia (shown in magenta) have invaded the worm’s gut cells (shown in yellow; the cells’ nuclei are shown in blue) and have instructed the cells to merge. The cell fusion enables the microsporidia to thrive and propagate in the expanded space. Scientists study microsporidia in worms to gain more insight into how these parasites manipulate their host cells. This knowledge might help researchers devise strategies to prevent or treat infections with microsporidia. For more on the research into microsporidia, see this news release from the University of California San Diego. Related to images 5778 and 5779.

Floral pattern emerging as two bacterial species, motile Acinetobacter baylyi (red) and non-motile Escherichia coli (green), are grown together for 48 hours on 1% agar surface from a small inoculum in the center of a Petri dish.

See 6557 for a photo of this process at 24 hours on 0.75% agar surface.
See 6553 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.

Two fruit fly (Drosophila melanogaster) egg cells, one on each side of the central black line. The colorful swirls show the circular movement of cytoplasm—called ooplasmic streaming—that occurs in late egg cell development in wild-type (right) and mutant (left) oocytes. This image was captured using confocal microscopy.

More information on the research that produced this image can be found in the Journal of Cell Biology paper “Ooplasmic flow cooperates with transport and anchorage in Drosophila oocyte posterior determination” by Lu et al.

A cell in interphase, at the start of mitosis: Chromosomes duplicate, and the copies remain attached to each other. 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.

This image shows an abnormal, tetrapolar mitosis. Chromosomes are highlighted pink. The cells shown are S3 tissue cultured cells from Xenopus laevis, African clawed frog.

Image showing that the edge zone (top of image) of the quail embryo shows no proliferating cells (cyan), unlike the interior zone (bottom of image). Non-proliferating cell nuclei are labeled green. This image was obtained as part of a study to understand cell migration in embryos. More specifically, cell proliferation at the edge of the embryo was studied by examining the cellular uptake of a chemical compound called BrDU, which incorporates into the DNA during the S-phase of the cell cycle. Here, the cells that are positive for BrDU uptake are labeled in cyan, while other non-proliferating cell nuclei are labeled green. Notice that the vast majority of BrDU+ cells are located far away from the edge, indicating that edge cells are mostly non-proliferating. An NIGMS grant to Professor Garcia was used to purchase the confocal microscope that collected this image. Related to image 2807 and video 2809.

A scanning electron microscope picture of a nerve ending. It has been broken open to reveal vesicles (orange and blue) containing chemicals used to pass messages in the nervous system.

High-resolution time lapse of epithelial (skin) cell migration and wound healing. It shows an image taken every 13 seconds over the course of almost 14 minutes. The images were captured with quantitative orientation-independent differential interference contrast (DIC) microscope (left) and a conventional DIC microscope (right).

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

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.

Video of high-resolution confocal images depicting vimentin immunofluorescence (green) and nuclei (blue) at the edge of a quail embryo yolk. These images were obtained as part of a study to understand cell migration in embryos. An NIGMS grant to Professor Garcia was used to purchase the confocal microscope that collected these images. Related to images 2807 and 2808.

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 image of a mammalian epithelial cell, captured in metaphase, was the winning image in the high- and super-resolution microscopy category of the 2012 GE Healthcare Life Sciences Cell Imaging Competition. The image shows microtubules (red), kinetochores (green) and DNA (blue). The DNA is fixed in the process of being moved along the microtubules that form the structure of the spindle.

The image was taken using the DeltaVision OMX imaging system, affectionately known as the "OMG" microscope, and was displayed on the NBC screen in New York's Times Square during the weekend of April 20-21, 2013. It was also part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

A cell nucleus (blue) surrounded by lipid droplets (yellow). Exogenously expressed, S-tagged UBXD8 (green) recruits endogenous p97/VCP (red) to the surface of lipid droplets in oleate-treated HeLa cells. Nucleus stained with DAPI.

The body uses a variety of ion channels to transport small molecules across cell membranes.

Shortly after a pregnant woman gives birth, her breasts start to secrete milk. This process is triggered by hormonal and genetic cues, including the protein Elf5. Scientists discovered that Elf5 also has another job--it staves off cancer. Early in the development of breast cancer, human breast cells often lose Elf5 proteins. Cells without Elf5 change shape and spread readily--properties associated with metastasis. This image shows cells in the mouse mammary gland that are lacking Elf5, leading to the overproduction of other proteins (red) that increase the likelihood of metastasis.

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.

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.

During embryonic development, transcription factors (proteins that regulate gene expression) govern the differentiation of cells into separate tissues and organs. Researchers at Cincinnati Children's Hospital Medical Center used mice to study the development of certain internal organs, including the liver, pancreas, duodenum (beginning part of the small intestine), gall bladder and bile ducts. They discovered that transcription factor Sox17 guides some cells to develop into liver cells and others to become part of the pancreas or biliary system (gall bladder, bile ducts and associated structures). The separation of these two distinct cell types (liver versus pancreas/biliary system) is complete by embryonic day 8.5 in mice. The transcription factors PDX1 and Hes1 are also known to be involved in embryonic development of the pancreas and biliary system. This image shows mouse cells at embryonic day 10.5. The green areas show cells that will develop into the pancreas and/or duodenum(PDX1 is labeled green). The blue area near the bottom will become the gall bladder and the connecting tubes (common duct and cystic duct) that attach the gall bladder to the liver and pancreas (Sox17 is labeled blue). The transcription factor Hes1 is labeled red. The image was not published. A similar image (different plane of the section) was published in: Sox17 Regulates Organ Lineage Segregation of Ventral Foregut Progenitor Cells Jason R. Spence, Alex W. Lange, Suh-Chin J. Lin, Klaus H. Kaestner, Andrew M. Lowy, Injune Kim, Jeffrey A. Whitsett and James M. Wells, Developmental Cell, Volume 17, Issue 1, 62-74, 21 July 2009. doi:10.1016/j.devcel.2009.05.012

This time-lapse video shows the emergence of a flower-like pattern in a mixture of two bacterial species, motile Acinetobacter baylyi and non-motile Escherichia coli (green), that are grown together for 24 hours on 0.75% agar surface from a small inoculum in the center of a Petri dish.

See 6557 for a photo of this process at 24 hours on 0.75% agar surface.
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.

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 image 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. The technology was also featured in the NIH Director’s Blog post The Amazing Brain: Tracking Molecular Events with Calling Cards.

Related to video

Bacillus anthracis (anthrax) cells being killed by a fluorescent trans-translation inhibitor, which disrupts bacterial protein synthesis. The inhibitor is naturally fluorescent and looks blue when it is excited by ultraviolet light in the microscope. This is a color version of Image 3481.

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.

Novel biosensor system maps the timing and location of Rac protein activation in a living mouse embryo fibroblast.

Cells move forward with lamellipodia and filopodia supported by networks and bundles of actin filaments. Proper, controlled cell movement is a complex process. Recent research has shown that an actin-polymerizing factor called the Arp2/3 complex is the key component of the actin polymerization engine that drives amoeboid cell motility. ARPC3, a component of the Arp2/3 complex, plays a critical role in actin nucleation. In this photo, the ARPC3+/+ fibroblast cells were fixed and stained with Alexa 546 phalloidin for F-actin (red) and DAPI to visualize the nucleus (blue). ARPC3+/+ fibroblast cells with lamellipodia leading edge. Related to images 3328, 3329, 3330, 3331, and 3333.

Stereo triplet of a sea urchin embryo stained to reveal actin filaments (orange) and microtubules (blue). This image is part of a series of images: 1047, 1048, 1049, 1050 and 1051.

This image shows hundreds of human embryonic stem cells in various stages of differentiating into neurons. Some cells have become neurons (red), while others are still precursors of nerve cells (green). The yellow is an imaging artifact resulting when cells in both stages are on top of each other. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Bean-shaped mitochondria are cells' power plants. These organelles have their own DNA and replicate independently. The highly folded inner membranes are the site of energy generation.

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.

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, 6591, 6592.

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