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.

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.

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

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

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

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Here, the researchers visualized nuclei in orange to help them study changes in how the yeast cells divided. Cell walls are shown in blue. This image was captured using spinning disk confocal microscopy.

Related to images 6969 and 6970.

What looks a little like distant planets with some mysterious surface features are actually assemblies of proteins normally found in the cell's nucleolus, 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 photo of nucleolus proteins in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows each of the nucleolus compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue). The researchers have found that these compartments 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, video 3791 and image 3792.

This slide shows the technologies that the Joint Center for Structural Genomics developed for going from gene to structure and how the technologies have been integrated into a high-throughput pipeline, including all of the steps from target selection, parallel expression, protein purification, automated crystallization trials, automated crystal screening, structure determination, validation, and publication.

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.

Detailed three-dimensional reconstruction of a tubular matrix in a thin section of the peripheral endoplasmic reticulum between the plasma membranes of the cell.
The endoplasmic reticulum (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.
Shown here is a three-dimensional representation of the peripheral ER microtubules. Related to images 5855 and 5856

This delicate, birdlike projection is an immature seed of the Arabidopsis plant. The part in blue shows the cell that gives rise to the endosperm, the tissue that nourishes the embryo. The cell is expressing only the maternal copy of a gene called MEDEA. This phenomenon, in which the activity of a gene can depend on the parent that contributed it, is called genetic imprinting. In Arabidopsis, the maternal copy of MEDEA makes a protein that keeps the paternal copy silent and reduces the size of the endosperm. In flowering plants and mammals, this sort of genetic imprinting is thought to be a way for the mother to protect herself by limiting the resources she gives to any one embryo. Featured in the May 16, 2006, issue of Biomedical Beat.

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.

In 2007, the FDA modified warfarin's label to indicate that genetic makeup may affect patient response to the drug. The widely used blood thinner is sold under the brand name Coumadin®. Scientists involved in the NIH Pharmacogenetics Research Network are investigating whether genetic information can be used to improve optimal dosage prediction for patients.

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.

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.

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.

Crystals of jack bean concanavalin A protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

Speckle microscopy analysis of actin cytoskeleton force. This is an example of NIH-supported research on single-cell analysis. Images in related series; Related to 2799, 2800, 2801, 2802 and 2803.

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.

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

Human cells with the gene that codes for the protein FIT2 deleted. Green indicates an endoplasmic reticulum (ER) resident protein. The lack of FIT2 affected the structure of the ER and caused the resident protein to cluster in ER membrane aggregates, seen as large, bright-green spots. Red shows where the degradation of cell parts—called autophagy—is taking place, and the nucleus is visible in blue. This image was captured using a confocal microscope.

The head of 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 light sheet microscope.

Related to images 6928 and 6932.

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 image captures the spiral-shaped ovary of an anglerfish in cross-section. Once matured, these eggs will be released in a gelatinous, floating mass. For some species of anglerfish, this egg mass can be up to 3 feet long and include nearly 200,000 eggs.

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

The photo shows a confocal microscopy image of perineuronal nets (PNNs), which are specialized extracellular matrix (ECM) structures in the brain. The PNN surrounds some nerve cells in brain regions including the cortex, hippocampus and thalamus. Researchers study the PNN to investigate their involvement stabilizing the extracellular environment and forming nets around nerve cells and synapses in the brain. Abnormalities in the PNNs have been linked to a variety of disorders, including epilepsy and schizophrenia, and they limit a process called neural plasticity in which new nerve connections are formed. To visualize the PNNs, researchers labeled them with Wisteria floribunda agglutinin (WFA)-fluorescein. Related to image 3742.

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.

Image of the colon of a mouse mono-colonized with Bacteroides fragilis (red) residing within the crypt channel. The red staining is due to an antibody to B. fragilis, the green staining is a general dye for the mouse cells (phalloidin, which stains F-actin) and the light blue glow is from a dye for visualizing the mouse cell nuclei (DAPI, which stains DNA). Bacteria from the human microbiome have evolved specific molecules to physically associate with host tissue, conferring resilience and stability during life-long colonization of the gut. Image is featured in October 2015 Biomedical Beat blog post Cool Images: A Halloween-Inspired Cell Collection.

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 3745.

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.

Cell showing overproduction of the ARTS protein (red). ARTS triggers apoptosis, as shown by the activation of caspase-3 (green) a key tool in the cell's destruction. The nucleus is shown in blue. Image is featured in October 2015 Biomedical Beat blog post Cool Images: A Halloween-Inspired Cell Collection.

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

This microscopic image shows a chromatin fiber--a DNA molecule bound to naturally occurring proteins.

These images show three stages of cell division in Xenopus XL177 cells, which are derived from tadpole epithelial cells. They are (from top): metaphase, anaphase and telophase. The microtubules are green and the chromosomes are blue. Related to 3443.

Related to image 5871.

The parasitic worm that causes schistosomiasis hatches in water and grows up in a freshwater snail, as shown here. Once mature, the worm swims back into the water, where it can infect people through skin contact. Initially, an infected person might have a rash, itchy skin, or flu-like symptoms, but the real damage is done over time to internal organs.

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

Developing spermatids (precursors of mature sperm cells) begin as small, round cells and mature into long-tailed, tadpole-shaped ones. In the sperm cell's head is the cell nucleus; in its tail is the power to outswim thousands of competitors to fertilize an egg. As seen in this microscopy image, fruit fly spermatids start out as groups of interconnected cells. A small lipid molecule called PIP2 helps spermatids tell their heads from their tails. Here, PIP2 (red) marks the nuclei and a cell skeleton-building protein called tubulin (green) marks the tails. When PIP2 levels are too low, some spermatids get mixed up and grow with their heads at the wrong end. Because sperm development is similar across species, studies in fruit flies could help researchers understand male infertility in humans.

A fruit fly ovary, shown here, contains as many as 20 eggs. Fruit flies are not merely tiny insects that buzz around overripe fruit--they are a venerable scientific tool. Research on the flies has shed light on many aspects of human biology, including biological rhythms, learning, memory and neurodegenerative diseases. Another reason fruit flies are so useful in a lab (and so successful in fruit bowls) is that they reproduce rapidly. About three generations can be studied in a single month. Related to image 3607.

Researchers used cryo-electron tomography (cryo-ET) to capture images of a rat pancreas cell that were then compiled and color-coded to produce a 3D reconstruction. Visible features include the folded sacs of the Golgi apparatus (copper), transport vesicles (medium-sized dark-blue circles), microtubules (neon-green rods), a mitochondria membrane (pink), ribosomes (small pale-yellow circles), endoplasmic reticulum (aqua), and lysosomes (large yellowish-green circles). See 6606 for a still image from the video.

This is a fibroblast, a connective tissue cell that plays an important role in wound healing. Normal fibroblasts have smooth edges. In contrast, this spiky cell is missing a protein that is necessary for proper construction of the cell's skeleton. Its jagged shape makes it impossible for the cell to move normally. In addition to compromising wound healing, abnormal cell movement can lead to birth defects, faulty immune function, and other health problems.

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

T cells are white blood cells that are important in defending the body against bacteria, viruses and other pathogens. Each T cell carries proteins, called T-cell receptors, on its surface that are activated when they come in contact with an invader. This activation sets in motion a cascade of biochemical changes inside the T cell to mount a defense against the invasion. Scientists have been interested for some time what happens after a T-cell receptor is activated. One obstacle has been to study how this signaling cascade, or pathway, proceeds inside T cells.

In this image, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The image shows two key steps during the signaling process: clustering of a protein called linker for activation of T cells (LAT) (blue) and polymerization of the cytoskeleton protein actin (red). The findings show that the T-cell receptor signaling proteins self-organize into separate physical and biochemical compartments. This new system of studying molecular pathways outside the cells will enable scientists to better understand how the immune system combats microbes or other agents that cause infection.

To learn more how researchers assembled this T-cell receptor pathway, see this press release from HHMI's Marine Biological Laboratory Whitman Center. Related to video 3786.

A zebrafish embryo showing its natural colors. Zebrafish have see-through eggs and embryos, making them ideal research organisms for studying the earliest stages of development. This image was taken in transmitted light under a polychromatic polarizing microscope.

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.

The cerebellum is the brain's locomotion control center. Every time you shoot a basketball, tie your shoe or chop an onion, your cerebellum fires into action. Found at the base of your brain, the cerebellum is a single layer of tissue with deep folds like an accordion. People with damage to this region of the brain often have difficulty with balance, coordination and fine motor skills. For a lower magnification, see image 3639.

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

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

The new highly efficient parallelized DelPhi software was used to calculate the potential map distribution of an entire virus, the adeno-associated virus, which is made up of more than 484,000 atoms. Despite the relatively large dimension of this biological system, resulting in 815x815x815 mesh points, the parallelized DelPhi, utilizing 100 CPUs, completed the calculations within less than three minutes. Related to image 3374.

Crystal structure of a protein with unknown function from Xanthomonas campestris, a plant pathogen. Eight copies of the protein crystallized to form a ring. Chosen as the December 2007 Protein Structure Initiative Structure of the Month.

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: image 1048, image 1049, image 1050, image 1051 and image 1052.

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 2513 and 2514 for other versions of this illustration. Featured in The Structures of Life.

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

RNA incorporated into the CRISPR surveillance complex is positioned to scan across foreign DNA. Cryo-EM density from a 3Å reconstruction is shown as a yellow mesh.