A 3D model of the human endoplasmic reticulum membrane protein complex (EMC) that identifies its nine essential subunits. The EMC plays an important role in making membrane proteins, which are essential for all cellular processes. This is the first atomic-level depiction of the EMC. Its structure was obtained using single-particle cryo-electron microscopy.

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.

This video shows an instance of abnormal mitosis where chromosomes are late to align. The video demonstrates the spindle checkpoint in action: just one unaligned chromosome can delay anaphase and the completion of mitosis. The cells shown are S3 tissue cultured cells from Xenopus laevis, African clawed frog.

This sculpture made of purple and clear glass beads depicts bacteriophage Phi174, a virus that infects bacteria. It rests on a surface that portrays an adaptive landscape, a conceptual visualization. The ridges represent the gene combinations associated with the greatest fitness levels of the virus, as measured by how quickly the virus can reproduce itself. Phi174 is an important model system for studies of viral evolution because its genome can readily be sequenced as it evolves under defined laboratory conditions.

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.

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.

Cross-section of skin anatomy shows layers and different tissue types.

These ripples of color represent the outer membrane of the nucleus inside an astrocyte, a star-shaped cell inside the brain. Some proteins (green) act as keys to unlock other proteins (red) that form gates to let small molecules in and out of the nucleus (blue). Visualizing these different cell components at the boundary of the astrocyte nucleus enables researchers to study the molecular and physiological basis of neurological disorders, such as hydrocephalus, a condition in which too much fluid accumulates in the brain, and scar formation in brain tissue leading to abnormal neuronal activity affecting learning and memory. Scientists have now identified a pathway may be common to many of these brain diseases and begun to further examine it to find ways to treat certain brain diseases and injuries.

This photo shows a Varian Unity Inova 900 MHz, 21.1 T standard bore magnet Nuclear Magnetic Resonnance (NMR) spectrometer. NMR spectroscopy provides data used to determine the structures of proteins in solution, rather than in crystal form, as in X-ray crystallography. The technique is limited to smaller proteins or protein fragments in a high throughput approach.

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.

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.

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.

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

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.

This scanning electron microscope (SEM) image shows podocytes--cells in the kidney that play a vital role in filtering waste from the bloodstream--from a patient with chronic kidney disease. This image first appeared in Princeton Journal Watch on October 4, 2013.

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. Related to image 3756.

3D reconstructions of two stages in the assembly of the bacterial ribosome created from time-resolved cryo-electron microscopy images. Ribosomes translate genetic instructions into proteins.

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

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.

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 (lateral view).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For more information about the illumated area go to 3559.

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.

As an egg cell develops, a process called polarization controls what parts ultimately become the embryo's head and tail. This picture shows an egg of the fruit fly Drosophila. Red and green mark two types of signaling proteins involved in polarization. Disrupting these signals can scramble the body plan of the embryo, leading to severe developmental disorders.

It has been said that gastrulation is the most important event in a person's life. This part of early embryonic development transforms a simple ball of cells and begins to define cell fate and the body axis. In a study published in Science magazine in March 2012, NIGMS grantee Bob Goldstein and his research group studied how contractions of actomyosin filaments in C. elegans and Drosophila embryos lead to dramatic rearrangements of cell and embryonic structure. This research is described in detail in the following article: "Triggering a Cell Shape Change by Exploiting Preexisting Actomyosin Contractions." In these images, myosin (green) and plasma membrane (red) are highlighted at four timepoints in gastrulation in the roundworm C. elegans. The blue highlights in the top three frames show how cells are internalized, and the site of closure around the involuting cells is marked with an arrow in the last frame. See related video 3334.

Atomic model of the membrane region of the mitochondrial ATP synthase built into a cryo-EM map at 3.6 Å resolution. ATP synthase is the primary producer of ATP in aerobic cells. Drugs that inhibit the bacterial ATP synthase, but not the human mitochondrial enzyme, can serve as antibiotics. This therapeutic approach was successfully demonstrated with the bedaquiline, an ATP synthase inhibitor now used in the treatment of extensively drug resistant tuberculosis.

More information about this structure can be found in the Science paper ”Atomic model for the dimeric F0 region of mitochondrial ATP synthase” by Guo et. al.

The chemical structure of the morphine molecule

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

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

Pretty in pink, the enzyme histone deacetylase (HDA6) stands out against a background of blue-tinted DNA in the nucleus of an Arabidopsis plant cell. Here, HDA6 concentrates in the nucleolus (top center), where ribosomal RNA genes reside. The enzyme silences the ribosomal RNA genes from one parent while those from the other parent remain active. This chromosome-specific silencing of ribosomal RNA genes is an unusual phenomenon observed in hybrid plants.

Crystal structure of oligoendopeptidase F, a protein slicing enzyme from Bacillus stearothermophilus, a bacterium that can cause food products to spoil. The crystal was formed using a microfluidic capillary, a device that enables scientists to independently control the parameters for protein crystal nucleation and growth. Featured as one of the July 2007 Protein Structure Initiative Structures of the Month.

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.

The marine bacterium Vibrio harveyi glows when near its kind. This luminescence, which results from biochemical reactions, is part of the chemical communication used by the organisms to assess their own population size and distinguish themselves from other types of bacteria. But V. harveyi only light up when part of a large group. This communication, called quorum sensing, speaks for itself here on a lab dish, where more densely packed areas of the bacteria show up blue. Other types of bacteria use quorum sensing to release toxins, trigger disease, and evade the immune system.

This image is featured on the poster for Dr. Rommie Amaro's 2017 Stetten Lecture. It depicts a detailed physical model of an influenza virus, incorporating information from several structural data sources. The small molecules around the virus are sialic acid molecules. The virus binds to and cleaves sialic acid as it enters and exits host cells. Researchers are building these highly detailed molecular scale models of different biomedical systems and then “bringing them to life” with physics-based methods, either molecular or Brownian dynamics simulations, to understand the structural dynamics of the systems and their complex interactions with drug or substrate molecules.

Motor neuron progenitors (green) were derived from human embryonic stem cells. Image and caption information courtesy of the California Institute for Regenerative Medicine.

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 2507 for an illustration with examples.

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.

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.

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.

Cells use bubble-like structures called vesicles (yellow) to import, transport, and export cargo and in cellular communication. A single cell may be filled with thousands of moving vesicles.

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

Cell-like compartments spontaneously emerge 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. Video created using epifluorescence microscopy.

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

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

Microscopy image of a tongue. One in a series of two, see image 5810

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 lined up.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, and 1019.

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

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.

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

Using a supercomputer to simulate the movement of atoms in a ribosome, researchers looked into the core of this protein-making nanomachine and took snapshots. The picture shows an amino acid (green) being delivered by transfer RNA (yellow) into a corridor (purple) in the ribosome. In the corridor, a series of chemical reactions will string together amino acids to make a protein. The research project, which tracked the movement of more than 2.6 million atoms, was the largest computer simulation of a biological structure to date. The results shed light on the manufacturing of proteins and could aid the search for new antibiotics, which typically work by disabling the ribosomes of bacteria.

A study published in March 2012 used cryo-electron microscopy to determine the structure of the DNA replication origin recognition complex (ORC), a semi-circular, protein complex (yellow) that recognizes and binds DNA to start the replication process. The ORC appears to wrap around and bend approximately 70 base pairs of double stranded DNA (red and blue). Also shown is the protein Cdc6 (green), which is also involved in the initiation of DNA replication. The video shows the structure from different angles. See related image 3597.

The structure of the endothelium, the thin layer of cells that line our arteries and veins, is visible here. The endothelium is like a gatekeeper, controlling the movement of materials into and out of the bloodstream. Endothelial cells are held tightly together by specialized proteins that function like strong ropes (red) and others that act like cement (blue).

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

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. 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. This image shows a pigment cell from zebrafish at high resolution. Related to images 5755, 5756, 5757 and 5758.

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.

This Petri dish contains microscopic roundworms called Caenorhabditis elegans. Researchers used these particular worms to study how C. elegans senses the color of light in its environment.

A robot is transferring 96 purification columns to a vacuum manifold for subsequent purification procedures.