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.

What looks like a Native American dream catcher is really a network of social interactions within a community. The red dots along the inner and outer circles represent people, while the different colored lines represent direct contact between them. All connections originate from four individuals near the center of the graph. Modeling social networks can help researchers understand how diseases spread.

A rendering of an activity biosensor image overlaid with a cell-centered frame of reference used for image analysis of signal transduction. This is an example of NIH-supported research on single-cell analysis. Related to 2798 , 2799, 2800, 2801 and 2803.

In this video, Rice University scientists used molecular modeling with a mathematical algorithm called AWSEM (for associative memory, water-mediated, structure and energy model) and structural data to analyze how a transcription factor called nuclear factor kappa B (NFkB) is removed from DNA to stop gene activation. AWSEM uses the interacting energies of their components to predict how proteins fold. At the start, the NFkB dimer (green and yellow, in the center) grips DNA (red, to the left), which activates the transcription of genes. IkB (blue, to the right), an inhibitor protein, stops transcription when it binds to NFkB and forces the dimer to twist and release its hold on DNA. The yellow domain at the bottom of IkB is the PEST domain, which binds first to NFkB. For more details about this mechanism called molecular stripping, see here.

Genes are often interrupted by stretches of DNA (introns, blue) that do not contain instructions for making a protein. The DNA segments that do contain protein-making instructions are known as exons (green). See image 2551 for a labeled version of this illustration. Featured in The New Genetics.

NIGMS-funded researchers led by Roger Kornberg solved the structure of RNA polymerase II. This is the enzyme in mammalian cells that catalyzes the transcription of DNA into messenger RNA, the molecule that in turn dictates the order of amino acids in proteins. For his work on the mechanisms of mammalian transcription, Kornberg received the Nobel Prize in Chemistry in 2006.

A crawling cell with DNA shown in blue and actin filaments, which are a major component of the cytoskeleton, visible in pink. Actin filaments help enable cells to crawl. This image was captured using structured illumination microscopy.

The signal is obtained by allowing proteins in human serum to interact with glycan (polysaccharide) arrays. The arrays are shown in replicate so the pattern is clear. Each spot contains a specific type of glycan. Proteins have bound to the spots highlighted in green.

Dynein (green) is a motor protein that “walks” along microtubules (red, part of the cytoskeleton) and carries its cargo along with it. This video was captured through fluorescence microscopy.

This image shows Q fever bacteria (yellow), which infect cows, sheep, and goats around the world and can infect humans, as well. When caught early, Q fever can be cured with antibiotics. A small fraction of people can develop a more serious, chronic form of the disease.

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

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 are starting to line up.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1017, 1018, 1019, and 1021.

An adult Hawaiian bobtail squid, Euprymna scolopes, (~4 cm) surrounded by newly hatched juveniles (~2 mm) in a bowl of seawater.

Related to image 7011 and video 7012.

Fluorescent markers show the interconnected web of tubes and compartments in the endoplasmic reticulum. The protein atlastin helps build and maintain this critical part of cells. The image is from a July 2009 news release.

An adult Hawaiian bobtail squid, Euprymna scolopes, swimming next to a submerged hand.

Related to image 7010 and video 7012.

This illustration shows pathogenic bacteria behave like a Trojan horse: switching from antibiotic susceptibility to resistance during infection. Salmonella are vulnerable to antibiotics while circulating in the blood (depicted by fire on red blood cell) but are highly resistant when residing within host macrophages. This leads to treatment failure with the emergence of drug-resistant bacteria.

This image was chosen as a winner of the 2016 NIH-funded research image call, and the research was funded in part by NIGMS.

An image of Caenorhabditis elegans, a tiny roundworm, showing internal structures including the intestine, pharynx, and body wall muscle. C. elegans is one of the simplest organisms with a nervous system. Scientists use it to study nervous system development, among other things. This image was captured with a quantitative orientation-independent differential interference contrast (OI-DIC) microscope. The scale bar is 100 µm.

More information about the microscopy that produced this image can be found in the Journal of Microscopy paper by Malamy and Shribak.

A cell in prometaphase during mitosis: The nuclear membrane breaks apart, and the spindle starts to interact with the chromosomes. 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.

The proteasome is a critical multiprotein complex in the cell that breaks down and recycles proteins that have become damaged or are no longer needed. This movie shows how a protein substrate (red) is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region then gets engaged by the AAA+ motor of the proteasome (cyan), which initiates mechanical pulling, unfolding and movement of the protein into the proteasome's interior for cleavage into shorter protein pieces called peptides. During movement of the substrate, its ubiquitin modification gets cleaved off by the deubiquitinase Rpn11 (green), which sits directly above the entrance to the AAA+ motor pore and acts as a gatekeeper to ensure efficient ubiquitin removal, a prerequisite for fast protein breakdown by the 26S proteasome. Related to image 3763.

Drugs enter different layers of skin via intramuscular, subcutaneous, or transdermal delivery methods. See image 2531 for an unlabeled version of this illustration. Featured in Medicines By Design.

Protein kinases—enzymes that add phosphate groups to molecules—are cancer chemotherapy targets because they play significant roles in almost all aspects of cell function, are tightly regulated, and contribute to the development of cancer and other diseases if any alterations to their regulation occur. Genetic abnormalities affecting the c-Abl tyrosine kinase are linked to chronic myelogenous leukemia, a cancer of immature cells in the bone marrow. In the noncancerous form of the protein, binding of a myristoyl group to the kinase domain inhibits the activity of the protein until it is needed (top left shows the inactive form, top right shows the open and active form). The cancerous variant of the protein, called Bcr-Abl, lacks this autoinhibitory myristoyl group and is continually active (bottom). ATP is shown in green bound in the active site of the kinase.

Find these in the RCSB Protein Data Bank: c-Abl tyrosine kinase and regulatory domains (PDB entry 1OPL) and F-actin binding domain (PDB entry 1ZZP).

In SARS-CoV-2, the virus that causes COVID-19, nucleocapsid is a complex molecule with many functional parts. One section folds into an RNA-binding domain, with a groove that grips a short segment of the viral genomic RNA. Another section folds into a dimerization domain that brings two nucleocapsid molecules together. The rest of the protein is intrinsically disordered, forming tails at each end of the protein chain and a flexible linker that connects the two structured domains. These disordered regions assist with RNA binding and orchestrate association of nucleocapsid dimers into larger assemblies that package the RNA in the small space inside virions. Nucleocapsid is in magenta and purple, and short RNA strands are in yellow.

Find these in the RCSB Protein Data Bank: RNA-binding domain (PDB entry 7ACT) and Dimerization domain (PDB entry 6WJI).

Crystal structure of the beta2-adrenergic receptor protein. This is the first known structure of a human G protein-coupled receptor, a large family of proteins that control critical bodily functions and the action of about half of today's pharmaceuticals. Featured as one of the November 2007 Protein Structure Initiative Structures of the Month.

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.

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.

This animation shows atoms of the HIV capsid, the shell that encloses the virus's genetic material. Scientists determined the exact structure of the capsid using a variety of imaging techniques and analyses. They then entered this data into a supercomputer to produce this image. Related to image 3477.

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 3436.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3415, 3417, 3418, and 3419.

The extracellular matrix (ECM) is most prevalent in connective tissues but also is present between the stems (axons) of nerve cells. The axons of nerve cells are surrounded by the ECM encasing myelin-supplying Schwann cells, which insulate the axons to help speed the transmission of electric nerve impulses along the axons.

Muscles stretch and contract when we walk, and skin splits open and knits back together when we get a paper cut. To study these contractile forces, researchers built a three-dimensional scaffold that mimics tissue in an organism. Researchers poured a mixture of cells and elastic collagen over microscopic posts in a dish. Then they studied how the cells pulled and released the posts as they formed a web of tissue. To measure forces between posts, the researchers developed a computer model. Their findings--which show that contractile forces vary throughout the tissue--could have a wide range of medical applications.

Mouse embryonic stem cells matured into this bundle of hair cells similar to the ones that transmit sound in the ear. These cells could one day be transplanted as a therapy for some forms of deafness, or they could be used to screen drugs to treat deafness. The hairs are shown at 23,000 times magnification via scanning electron microscopy. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Like a major city, a cell teems with specialized workers that carry out its daily operations--making energy, moving proteins, or helping with other tasks. Researchers took microscopic pictures of thin layers of a cell and then combined them to make this 3-D image featuring color-coded organelles--the cell's "workers." Using this image, scientists can understand how these specialized components fit together in the cell's packed inner world.

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.

A mouse's fat cells (red) are shown surrounded by a network of blood vessels (green). Fat cells store and release energy, protect organs and nerve tissues, insulate us from the cold, and help us absorb important vitamins.

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

Using an electrode, researchers apply an electrical pulse onto a piece of muscle tissue affected by Huntington's disease.

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Stained cell membranes (green) and cell walls (red) reveal the connections between cells. Younger cells take up more cell membrane stain, while older cells take up more cell wall stain, leading to the color differences seen here. This image was captured using spinning disk confocal microscopy.

Related to images 6970 and 6971.

This pig cell is in the process of dividing. The chromosomes (purple) have already replicated and the duplicates are being pulled apart by fibers of the cell skeleton known as microtubules (green). Studies of cell division yield knowledge that is critical to advancing understanding of many human diseases, including cancer and birth defects.

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

This photograph of kidney tissue, taken using fluorescent light microscopy, shows a close-up view of part of image 3723. Kidneys filter the blood, removing waste and excessive fluid, which is excreted in urine. The filtration system is made up of components that include glomeruli (for example, the round structure taking up much of the image's center is a glomerulus) and tubules (seen in cross-section here with their inner lining stained green). Related to image 3675 .

Nucleotides in DNA are copied into RNA, where they are read three at a time to encode the amino acids in a protein. Many parts of a protein fold as the amino acids are strung together.

See image 2510 for a labeled version of this illustration.

Featured in The Structures of Life.

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.

A 3-D model of the alkaloid serratezomine A shows the molecule's complex ring structure.

Thin, hair-like biological structures called cilia are tiny but mighty. Each one, made up of more than 600 different proteins, works together with hundreds of others in a tightly-packed layer to move like a crowd at a ball game doing "the wave." Their synchronized motion helps sweep mucus from the lungs and usher eggs from the ovaries into the uterus. By controlling how fluid flows around an embryo, cilia also help ensure that organs like the heart develop on the correct side of your body.

Active site of E. coli response regulator PhoB.

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.

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

A crystal of RNase A protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

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.

A mouse liver glows after being tagged with specially designed infrared-fluorescent protein (IFP). Since its discovery in 1962, green fluorescent protein (GFP) has become an invaluable resource in biomedical imaging. But because of its short wavelength, the light that makes GFP glow doesn't penetrate far in whole animals. So University of California, San Diego cell biologist Roger Tsien--who shared the 2008 Nobel Prize in chemistry for groundbreaking work with GFP--made infrared-fluorescent proteins (IFPs) that shine under longer-wavelength light, allowing whole-body imaging in small animals.

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 plasma membrane is a cell's protective barrier. See image 2523 for an unlabeled version of this illustration. Featured in The Chemistry of Health.

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.