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.

Arranging exons in different patterns, called alternative splicing, enables cells to make different proteins from a single gene. Featured in The New Genetics.

See image 2552 for an unlabeled version of this illustration.

Acetylsalicylate (bottom) is the aspirin of today. Adding a chemical tag called an acetyl group (shaded box, bottom) to a molecule derived from willow bark (salicylate, top) makes the molecule less acidic (and easier on the lining of the digestive tract), but still effective at relieving pain. See image 2530 for a labeled 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).

A number of environmental factors cause DNA mutations that can lead to cancer: toxins in cigarette smoke, sunlight and other radiation, and some viruses.

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 illustration shows a protein substrate (red) that is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region 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 small 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 video 3764.

E. coli bacteria normally live harmlessly in our intestines, but some cause disease by making toxins. One of these toxins, called Shiga toxin (green), inactivates host ribosomes (purple) by mimicking their normal binding partners, the EF-Tu elongation factor (red) complexed with Phe-tRNAPhe (orange).

Find these in the RCSB Protein Data Bank: Shiga toxin 2 (PDB entry 7U6V) and Phe-tRNA (PDB entry 1TTT).

More information about this work can be found in the J. Biol. Chem. paper "Cryo-EM structure of Shiga toxin 2 in complex with the native ribosomal P-stalk reveals residues involved in the binding interaction" by Kulczyk et. al.

The green in this image highlights a protein called TonB, which is produced by many gram-negative bacteria, including those that cause typhoid fever, meningitis and dysentery. TonB lets bacteria take up iron from the host's body, which they need to survive. More information about the research behind this image can be found in a Biomedical Beat Blog posting from August 2013.

The microtubule severing protein, katanin, localizes to chromosomes and regulates anaphase A in mitosis. The movement of chromosomes on the mitotic spindle requires the depolymerization of microtubule ends. The figure shows the mitotic localization of the microtubule severing protein katanin (green) relative to spindle microtubules (red) and kinetochores/chromosomes (blue). Katanin targets to chromosomes during both metaphase (top) and anaphase (bottom) and is responsible for inducing the depolymerization of attached microtubule plus-ends. This image was a finalist in the 2008 Drosophila Image Award.

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

Microarrays, also called gene chips, are tools that let scientists track the activity of hundreds or thousands of genes simultaneously. For example, researchers can compare the activities of genes in healthy and diseased cells, allowing the scientists to pinpoint which genes and cell processes might be involved in the development of a disease.

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 1052.

The long, stringy DNA that makes up genes is spooled within chromosomes inside the nucleus of a cell. (Note that a gene would actually be a much longer stretch of DNA than what is shown here.) See image 2540 for a labeled version of this illustration. Featured in The New Genetics.

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool.

Frame 1 shows the two components of the CRISPR system: a strong cutting device (an enzyme called Cas9 that can cut through a double strand of DNA), and a finely tuned targeting device (a small strand of RNA programmed to look for a specific DNA sequence).

In frame 2, the CRISPR machine locates the target DNA sequence once inserted into a cell.

In frame 3, the Cas9 enzyme cuts both strands of the DNA.

Frame 4 shows a repaired DNA strand with new genetic material that researchers can introduce, which the cell automatically incorporates into the gap when it repairs the broken DNA.

For an explanation and overview of the CRISPR-Cas9 system, see the iBiology video.

Download the individual frames: Frame 1, Frame 2, Frame 3, and Frame 4.

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.

An atomic force microscopy image shows DNA folded into an intricate, computer-designed structure. Image is featured on Biomedical Beat blog post Cool Image: DNA Origami. See also related image 3689 .

The cerebellum of a mouse is shown here in cross-section. 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 higher magnification, see image 3371.

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

Ribonucleic acid (RNA) has a sugar-phosphate backbone and the bases adenine (A), cytosine (C), guanine (G), and uracil (U). Featured in The New Genetics.

See image 2554 for an unlabeled version of this illustration.

Each of the tiny colored specs in this image is a cell on the surface of a fish scale. To better understand how wounds heal, scientists have inserted genes that make cells brightly glow in different colors into the skin cells of zebrafish, a fish often used in laboratory research. The colors enable the researchers to track each individual cell, for example, as it moves to the location of a cut or scrape over the course of several days. These technicolor fish endowed with glowing skin cells dubbed "skinbow" provide important insight into how tissues recover and regenerate after an injury.

For more information on skinbow fish, see the Biomedical Beat blog post Visualizing Skin Regeneration in Real Time and a press release from Duke University highlighting this research. Related to image 3782.

About half of all human proteins include chains of sugar molecules that are critical for the proteins to function properly. Appears in the NIGMS booklet Inside the Cell.

A peripheral nerve cell made from human embryonic stem cell-derived neural crest stem cells. The nucleus is shown in blue, and nerve cell proteins peripherin and beta-tubulin (Tuj1) are shown in green and red, respectively. Related to image 3263.

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.

Cells progress through a cycle that consists of phases for growth (blue, green, yellow) and division (red). Cells become quiescent when they exit this cycle (purple). See image 2499 for a labeled version of this illustration.

This lab space was designed for work on the induced pluripotent stem (iPS) cell collection, part of the NIGMS Human Genetic Cell Repository at the Coriell Institute for Medical Research.

Network diagram showing a map of protein-protein interactions in a yeast (Saccharomyces cerevisiae) cell. This cluster includes 78 percent of the proteins in the yeast proteome. The color of a node represents the phenotypic effect of removing the corresponding protein (red, lethal; green, nonlethal; orange, slow growth; yellow, unknown).

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 stereo microscope.

Related to images 6927 and 6928.

A research mentor (Lori Eidson) and student (Nina Waldron, on the microscope) were 2009 members of the BRAIN (Behavioral Research Advancements In Neuroscience) program at Georgia State University in Atlanta. This program is an undergraduate summer research experience funded in part by NIGMS.

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. This image shows neural crest cell-derived, migrating pigment cells in a salamander. 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. Related to images 5754, 5755, 5756 and 5757.

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.

The plasma membrane is a cell's protective barrier. See image 2524 for a labeled version of this illustration. Featured in The Chemistry of Health.

Hepatocytes, like the one shown here, are the most abundant type of cell in the human liver. They play an important role in building proteins; producing bile, a liquid that aids in digesting fats; and chemically processing molecules found normally in the body, like hormones, as well as foreign substances like medicines and alcohol.

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

A biofilm is a highly organized community of microorganisms that develops naturally on certain surfaces. These communities are common in natural environments and generally do not pose any danger to humans. Many microbes in biofilms have a positive impact on the planet and our societies. Biofilms can be helpful in treatment of wastewater, for example. This dime-sized biofilm, however, was formed by the opportunistic pathogen Pseudomonas aeruginosa. Under some conditions, this bacterium can infect wounds that are caused by severe burns. The bacterial cells release a variety of materials to form an extracellular matrix, which is stained red in this photograph. The matrix holds the biofilm together and protects the bacteria from antibiotics and the immune system.

A computer-generated sketch of a DNA origami folded into a flower-and-bird structure. See also related image 3690.

A genetic disorder of the nervous system, neurofibromatosis causes tumors to form on nerves throughout the body, including a type of tumor called an optic nerve glioma that can result in childhood blindness. The image was used to demonstrate the unique imaging capabilities of one of our newest (at the time) laser scanning microscopes and is of a wildtype (normal) mouse retina in the optic fiber layer. This layer is responsible for relaying information from the retina to the brain and was fluorescently stained to reveal the distribution of glial cells (green), DNA and RNA in the cell bodies of the retinal ganglion neurons (orange) and their optic nerve fibers (red), and actin in endothelial cells surrounding a prominent branching blood vessel (blue). By studying the microscopic structure of normal and diseased retina and optic nerves, we hope to better understand the altered biology of the tissues in these tumors with the prospects of developing therapeutic interventions.

DNA (blue) and actin (red) in cultured fibroblast cells.

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 3725 and 3675.

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.

Related to images 1010, 1011, 1012, 1014, 1015, 1016, 1017, 1018, 1019, and 1021.

The Golgi complex, also called the Golgi apparatus or, simply, the Golgi. This organelle receives newly made proteins and lipids from the ER, puts the finishing touches on them, addresses them, and sends them to their final destinations.

Crystals of fungal lipase protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

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.

This 2-hour-old fly embryo already has a blueprint for its formation, and the process for following it is so precise that the difference of just a few key molecules can change the plans. Here, blue marks a high concentration of Bicoid, a key signaling protein that directs the formation of the fly's head. It also regulates another important protein, Hunchback (green), that further maps the head and thorax structures and partitions the embryo in half (red is DNA). The yellow dots overlaying the embryo plot the concentration of Bicoid versus Hunchback proteins within each nucleus. The image illustrates the precision with which an embryo interprets and locates its halfway boundary, approaching limits set by simple physical principles. This image was a finalist in the 2008 Drosophila Image Award.

The nucleolinus is a cellular compartment that has been a lonely bystander in scientific endeavors. Although it's found in a range of species, its function has been mysterious—mainly because the structure is hard to visualize. An August 2010 study showed that the nucleolinus is crucial for cell division. When researchers zapped the structure with a laser, an egg cell didn't complete division. When the oocyte was fertilized after laser microsurgery (bottom right), the resulting zygote didn't form vital cell division structures (blue and yellow).

A zebrafish embryo. The blue areas are cell bodies, the green lines are blood vessels, and the red glow is blood. This image was created by stitching together five individual images captured with a hyperspectral multipoint confocal fluorescence microscope that was developed at the Eliceiri Lab.

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

Model of an enzyme, dUTP pyrophosphatase, from Mycobacterium tuberculosis. Drugs targeted to this enzyme might inhibit the replication of the bacterium that causes most cases of tuberculosis.

The structure of the pore-forming protein VDAC-1 from humans. This molecule mediates the flow of products needed for metabolism--in particular the export of ATP--across the outer membrane of mitochondria, the power plants for eukaryotic cells. VDAC-1 is involved in metabolism and the self-destruction of cells--two biological processes central to health.

Related to images 2491, 2494, and 2488.

DNA consists of two long, twisted chains made up of nucleotides. Each nucleotide contains one base, one phosphate molecule, and the sugar molecule deoxyribose. The bases in DNA nucleotides are adenine, thymine, cytosine, and guanine. See image 2541 for an unlabeled version of this illustration. Featured in The New Genetics.

Borrelia burgdorferi is a spirochete, a class of long, slender bacteria that typically take on a coiled shape. Infection with this bacterium causes Lyme disease.

This short video shows a model of the DNA helicase in yeast. This DNA helicase has 11 proteins that work together to unwind DNA during the process of copying it, called DNA replication. Scientists used a technique called cryo-electron microscopy (cryo-EM), which allowed them to study the helicase structure in solution rather than in static crystals. Cryo-EM in combination with computer modeling therefore allows researchers to see movements and other dynamic changes in the protein. The cryo-EM approach revealed the helicase structure at much greater resolution than could be obtained before. The researchers think that a repeated motion within the protein as shown in the video helps it move along the DNA strand. To read more about DNA helicase and this proposed mechanism, see this news release by Brookhaven National Laboratory.

Both instruments shown were developed by CellFree Sciences of Yokohama, Japan. The instrument on the left, the GeneDecoder 1000, can generate 384 proteins from their corresponding genes, or gene fragments, overnight. It is used to screen for properties such as level of protein production and degree of solubility. The instrument on the right, the Protemist Protein Synthesizer, is used to generate the larger amounts of protein needed for protein structure determinations.