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.

Researchers use cluster analysis to study protein shape and function. Each green circle represents one potential shape of the protein mitoNEET. The longer the blue line between two circles, the greater the differences between the shapes. Most shapes are similar; they fall into three clusters that are represented by the three images of the protein. From a Rice University news release. Graduate student Elizabeth Baxter and Patricia Jennings, professor of chemistry and biochemistry at UCSD, collaborated with José Onuchic, a physicist at Rice University, on this work.

The nucleus of a degenerating human tendon cell, also known as a tenocyte. It has been color-coded based on the density of chromatin—a substance made up of DNA and proteins. Areas of low chromatin density are shown in blue, and areas of high chromatin density are shown in red. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6887 and 6888.

Wound healing requires the action of stem cells. In mice that lack the Sept2/ARTS gene, stem cells involved in wound healing live longer and wounds heal faster and more thoroughly than in normal mice. This confocal microscopy image from a mouse lacking the Sept2/ARTS gene shows a tail wound in the process of healing. See more information in the article in Science.

Related to images 3497 and 3498.

Microtubules (magenta) in neurons of the hippocampus, a part of the brain involved in learning and memory. Microtubules are strong, hollow fibers that provide structural support to cells. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6889, 6891, and 6892.

Yeast make bread, beer, and wine. And like us, yeast can reproduce sexually. A mother and father cell fuse and create one large cell that contains four offspring. When environmental conditions are favorable, the offspring are released, as shown here. Yeast are also a popular study subject for scientists. Research on yeast has yielded vast knowledge about basic cellular and molecular biology as well as about myriad human diseases, including colon cancer and various metabolic disorders.

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

These smooth muscle cells were derived from human embryonic stem cells. The nuclei are stained blue, and the proteins of the cytoskeleton are stained green. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Trypanosoma brucei is a single-cell parasite that causes sleeping sickness in humans. Scientists have been studying trypanosomes for some time because of their negative effects on human and also animal health, especially in sub-Saharan Africa. Moreover, because these organisms evolved on a separate path from those of animals and plants more than a billion years ago, researchers study trypanosomes to find out what traits they may harbor that are common to or different from those of other eukaryotes (i.e., those organisms having a nucleus and mitochondria). This image shows the T. brucei cell membrane in red, the DNA in the nucleus and kinetoplast (a structure unique to protozoans, including trypanosomes, which contains mitochondrial DNA) in blue and nuclear pore complexes (which allow molecules to pass into or out of the nucleus) in green. Scientists have found that the trypanosome nuclear pore complex has a unique mechanism by which it attaches to the nuclear envelope. In addition, the trypanosome nuclear pore complex differs from those of other eukaryotes because its components have a near-complete symmetry, and it lacks almost all of the proteins that in other eukaryotes studied so far are required to assemble the pore.

The "epigenetic code" controls gene activity with chemical tags that mark DNA (purple diamonds) and the "tails" of histone proteins (purple triangles). These markings help determine whether genes will be transcribed by RNA polymerase. Genes hidden from access to RNA polymerase are not expressed. See image 2562 for an unlabeled version of this illustration. Featured in The New Genetics.

Ribosomes manufacture proteins based on mRNA instructions. Each ribosome reads mRNA, recruits tRNA molecules to fetch amino acids, and assembles the amino acids in the proper order.

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

Here, bubonic plague bacteria (yellow) are shown in the digestive system of a rat flea (purple). The bubonic plague killed a third of Europeans in the mid-14th century. Today, it is still active in Africa, Asia, and the Americas, with as many as 2,000 people infected worldwide each year. If caught early, bubonic plague can be treated with antibiotics.

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

This is a magnified view of an Arabidopsis thaliana leaf a few days after being exposed to the pathogen Hyaloperonospora arabidopsidis. The plant from which this leaf was taken is genetically resistant to the pathogen. The spots in blue show areas of localized cell death where infection occurred, but it did not spread. Compare this response to that shown in Image 2782. Jeff Dangl has been funded by NIGMS to study the interactions between pathogens and hosts that allow or suppress infection.

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 3793.

This fingertip-shaped group of lights is a microscopic crystal called a quantum dot. About 10,000 times thinner than a sheet of paper, the dot radiates brilliant colors under ultraviolet light. Dots such as this one allow researchers to label and track individual molecules in living cells and may be used for speedy disease diagnosis, DNA testing, and screening for illegal drugs.

The nucleus contains the DNA of eukaryotic cells. The double membrane that bounds the nucleus flows into the rough endoplasmic reticulum, an organelle studded with ribosomes that manufacture membrane-bound proteins for the rest of the cell.

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.

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).

In this image, viewed with a ZEISS ORION NanoFab microscope, the community of cells lining a mouse airway is magnified more than 10,000 times. This collection of cells, known as the mucociliary escalator, is also found in humans. It is our first line of defense against inhaled bacteria, allergens, pollutants, and debris. Malfunctions in the system can cause or aggravate lung infections and conditions such as asthma and chronic obstructive pulmonary disease. The cells shown in gray secrete mucus, which traps inhaled particles. The colored cells sweep the mucus layer out of the lungs.

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

Along with blood vessels (red) and nerve cells (green), this mouse brain shows abnormal protein clumps known as plaques (blue). These plaques multiply in the brains of people with Alzheimer's disease and are associated with the memory impairment characteristic of the disease. Because mice have genomes nearly identical to our own, they are used to study both the genetic and environmental factors that trigger Alzheimer's disease. Experimental treatments are also tested in mice to identify the best potential therapies for human patients.

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

Axolotls—a type of salamander—that have been genetically modified so that various parts of their nervous systems glow purple and green. 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 6932.

These images illustrate a technique combining cryo-electron tomography and super-resolution fluorescence microscopy called correlative imaging by annotation with single molecules (CIASM). CIASM enables researchers to identify small structures and individual molecules in cells that they couldn’t using older techniques.

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

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.

Superresolution microscopy work on endoplasmic reticulum (ER) in the peripheral areas of the cell showing details of the structure and arrangement in a complex web of tubes.
The 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. The ER has a flexible structure to allow it to accomplish these tasks by changing shape as conditions in the cell change. Shown here an image created by super-resolution microscopy of the ER in the peripheral areas of the cell showing details of the structure and the arrangements in a complex web of tubes. Related to images 5856 and 5857.

This image shows a cell in two stages of division: prometaphase (top) and metaphase (bottom). To form identical daughter cells, chromosome pairs (blue) separate via the attachment of microtubules made up of tubulin proteins (pink) to specialized structures on centromeres (green).

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 in Scotland were the first to clone an animal, this sheep named Dolly. She later gave birth to Bonnie, the lamb next to her.

Model of an enzyme, PanB, from Mycobacterium tuberculosis, the bacterium that causes most cases of tuberculosis. This enzyme is an attractive drug target.

These images model the molecular structures of three enzymes with critical roles in the life cycle of the human immunodeficiency virus (HIV). At the top, reverse transcriptase (orange) creates a DNA copy (yellow) of the virus's RNA genome (blue). In the middle image, integrase (magenta) inserts this DNA copy in the DNA genome (green) of the infected cell. At the bottom, much later in the viral life cycle, protease (turquoise) chops up a chain of HIV structural protein (purple) to generate the building blocks for making new viruses. See these enzymes in action on PDB 101’s video A Molecular View of HIV Therapy.

A light microscope image of cells 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, two cells have formed after a round of mitosis.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, and 1021.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Using X-ray crystallography, researchers determined the structure of a CCD-1 molecule and a molecule of the antibiotic cefotaxime bound together. The structure revealed that CCD-1 provides extensive hydrogen bonding and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6767.

Bioengineers were able to coax bacteria to blink in unison on microfluidic chips. This image shows a small chip with about 500 blinking bacterial colonies or biopixels. Related to images 3265 and 3268. From a UC San Diego news release, "Researchers create living 'neon signs' composed of millions of glowing bacteria."

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 red) have invaded the worm’s gut cells (the large blue dots are the cells' nuclei) 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 5777 and 5778.

These images show frog cells in interphase. The cells are Xenopus XL177 cells, which are derived from tadpole epithelial cells. The microtubules are green and the chromosomes are blue. Related to 3442.

Enzymes convert substrates into products very quickly. See image 2522 for a labeled version of this illustration. Featured in The Chemistry of Health.

Solution NMR structure of protein target WR41 (left) from C. elegans. Noting the unanticipated structural similarity to the ubiquitin protein (Ub) found in all eukaryotic cells, researchers discovered that WR41 is a Ub-like modifier, ubiquitin-fold modifier 1 (Ufm1), on a newly uncovered ubiquitin-like pathway. Subsequently, the PSI group also determined the three-dimensional structure of protein target HR41 (right) from humans, the E2 ligase for Ufm1, using both NMR and X-ray crystallography.

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.

A red poppy.

Mosquito larvae with genes edited by CRISPR swimming in water. This species of mosquito, Culex quinquefasciatus, can transmit West Nile virus, Japanese encephalitis virus, and avian malaria, among other diseases. The researchers who took this video optimized the gene-editing tool CRISPR for Culex quinquefasciatus that could ultimately help stop the mosquitoes from spreading pathogens. The work is described in the Nature Communications paper "Optimized CRISPR tools and site-directed transgenesis towards gene drive development in Culex quinquefasciatus mosquitoes" by Feng et al. Related to images 6769 and 6770.

A shell from the venomous cone snail Conus omaria, which lives in the Pacific and Indian oceans and eats other snails. University of Utah scientists discovered a new toxin in this snail species' venom, and say it will be a useful tool in designing new medicines for a variety of brain disorders, including Alzheimer's and Parkinson's diseases, depression, nicotine addiction and perhaps schizophrenia.

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 (dark oval shapes) invaded the worm’s gut cells (long tube; the cell nuclei are shown in red) 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 5777 and 5779.

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.

Proteins are long chains of amino acids. Each protein has a unique amino acid sequence. It is still a mystery how a protein folds into the proper shape based on its sequence. Scientists hope that one day they can "watch" this folding process for any given protein. The dream has been realized, at least partially, through the use of computer simulation.

Like a paint-by-numbers picture, painted probes tint individual human chromosomes by targeting specific DNA sequences. Chromosome 13 is colored green, chromosome 14 is in red and chromosome 15 is painted yellow. The image shows two examples of fused chromosomes—a pair of chromosomes 15 connected head-to-head (yellow dumbbell-shaped structure) and linked chromosomes 13 and 14 (green and red dumbbell). These fused chromosomes—called dicentric chromosomes—may cause fertility problems or other difficulties in people.

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.

This is a tomographic reconstruction of a mitochondrion from an insect flight muscle. Mitochondria are cellular compartments that are best known as the powerhouses that convert energy from the food into energy that runs a range of biological processes. Nearly all our cells have mitochondria.

Dose-response curves determine how much of a drug (X-axis) causes a particular effect, or a side effect, in the body (Y-axis). Featured in Medicines By Design.

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.