What looks like the gossamer wings of a butterfly is actually the retina of a mouse, delicately snipped to lay flat and sparkling with fluorescent molecules. The image is from a research project investigating the promise of gene therapy for glaucoma. It was created at an NIGMS-funded advanced microscopy facility that develops technology for imaging across many scales, from whole organisms to cells to individual molecules.

The ability to obtain high-resolution imaging of tissue as large as whole mouse retinas was made possible by a technique called large-scale mosaic confocal microscopy, which was pioneered by the NIGMS-funded National Center for Microscopy and Imaging Research. The technique is similar to Google Earth in that it computationally stitches together many small, high-resolution images.

Genome editing using CRISPR/Cas9 is a rapidly expanding field of scientific research with emerging applications in disease treatment, medical therapeutics and bioenergy, just to name a few. This technology is now being used in laboratories all over the world to enhance our understanding of how living biological systems work, how to improve treatments for genetic diseases and how to develop energy solutions for a better future.

A global "map of the protein structure universe" indicating the positions of specific proteins. The preponderance of small, less-structured proteins near the origin, with the more highly structured, large proteins towards the ends of the axes, may suggest the evolution of protein structures.

To better understand cell movements in developing embryos, researchers isolated cells from early zebrafish embryos and grew them as clusters. Provided with the right signals, the clusters replicated some cell movements seen in intact embryos. Each line in this image depicts the movement of a single cell. The image was created using time-lapse confocal microscopy. Related to video 6776.

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.

The TRPA1 protein is responsible for the burn you feel when you taste a bite of sushi topped with wasabi. Known therefore informally as the "wasabi receptor," this protein forms pores in the membranes of nerve cells that sense tastes or odors. Pungent chemicals like wasabi or mustard oil cause the pores to open, which then triggers a tingling or burn on our tongue. This receptor also produces feelings of pain in response to chemicals produced within our own bodies when our tissues are damaged or inflamed. Researchers used cryo-EM to reveal the structure of the wasabi receptor at a resolution of about 4 angstroms (a credit card is about 8 million angstroms thick). This detailed structure can help scientists understand both how we feel pain and how we can limit it by developing therapies to block the receptor. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail.

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.

Meiosis is the process whereby a cell reduces its chromosomes from diploid to haploid in creating eggs or sperm. See image 2545 for an unlabeled version of this illustration. See image 2544 for an unlabeled version of this illustration. Featured in The New Genetics.

The lubber grasshopper, found throughout the southern United States, is frequently used in biology classes to teach students about the respiratory system of insects. Unlike mammals, which have red blood cells that carry oxygen throughout the body, insects have breathing tubes that carry air through their exoskeleton directly to where it's needed. This image shows the breathing tubes embedded in the weblike sheath cells that cover developing egg chambers.

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

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

This painting shows a cross section of a small respiratory droplet, like the ones that are thought to transmit SARS-CoV-2, the virus that causes COVID-19. The virus is shown in pink, and the droplet is also filled with molecules that are present in the respiratory tract, including mucins (green), pulmonary surfactant proteins and lipids (blue), and antibodies (tan).

Amid a network of blood vessels and star-shaped support cells, neurons in the brain signal each other. The mists of color show the flow of important molecules like glucose and oxygen. This image is a snapshot from a 52-second simulation created by an animation artist. Such visualizations make biological processes more accessible and easier to understand.

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.

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.

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.

Duplicated pair of chromosomes have exchanged material.

This eerily glowing blob isn't an alien or a creature from the deep sea--it's a mouse embryo just eight and a half days old. The green shell and core show a protein called Smad4. In the center, Smad4 is telling certain cells to begin forming the mouse's liver and pancreas. Researchers identified a trio of signaling pathways that help switch on Smad4-making genes, starting immature cells on the path to becoming organs. The research could help biologists learn how to grow human liver and pancreas tissue for research, drug testing and regenerative medicine. In addition to NIGMS, NIH's National Institute of Diabetes and Digestive and Kidney Diseases also supported this work.

Cells move forward with lamellipodia and filopodia supported by networks and bundles of actin filaments. Proper, controlled cell movement is a complex process. Recent research has shown that an actin-polymerizing factor called the Arp2/3 complex is the key component of the actin polymerization engine that drives amoeboid cell motility. ARPC3, a component of the Arp2/3 complex, plays a critical role in actin nucleation. In this photo, the ARPC3+/+ fibroblast cells were fixed and stained with Alexa 546 phalloidin for F-actin (red), mDia1 (green), and DAPI to visualize the nucleus (blue). mDia1 is localized at the lamellipodia of ARPC3+/+ fibroblast cells. Related to images 3328, 3329, 3331, 3332, and 3333.

A zebrafish head with blood vessels shown in purple. Researchers often study zebrafish because they share many genes with humans, grow and reproduce quickly, and have see-through eggs and embryos, which make it easy to study early stages of development.

This image was captured using a light sheet microscope.

Related to video 6933.

T cells engulf and digest cells displaying markers (or antigens) for retroviruses, such as HIV.

Endocytosis is the process by which cells are able to take up membrane and extracellular materials through the formation of a small intracellular bubble, called a vesicle. This process, called membrane budding, is generally by a coating of proteins. This protein coat helps both to deform the membrane and to concentrate specific proteins inside the newly forming vesicle. Clathrin is a coat protein that functions in receptor-mediated endocytosis events at the plasma membrane. This animation shows the process of clathrin-mediated endocytosis. An iron-transport protein called transferrin (blue) is bound to its receptor (purple) on the exterior cell membrane.  Inside the cell, a clathrin cage (shown in white/beige) assembles through interactions with membrane-bound adaptor proteins (green), causing the cell membrane to begin bending. The adaptor proteins also bind to receptors for transferrin, capturing them in the growing vesicle. Molecules of a protein called dynamin (purple) are then recruited to the neck of the vesicle and are involved in separating the membranes of the cell and the vesicle. Soon after the vesicle has budded off the membrane, the clathrin cage is disassembled. This disassembly is mediated by another protein called HSC70 (yellow), and its cofactor protein auxilin (orange).

Novel biosensor system maps the timing and location of Rac protein activation in a living mouse embryo fibroblast.

CellPack image of the H1N1 influenza virus, with hemagglutinin and neuraminidase glycoproteins in green and red, respectively, on the outer envelope (white); matrix protein in gray, and ribonucleoprotein particles inside the virus in red and green. Related to image 6356.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to images 3413, 3414, 3415, 3416, 3417, and 3419.

The largest human cell (by volume) is the egg. Human eggs are 150 micrometers in diameter and you can just barely see one with a naked eye. In comparison, consider the eggs of chickens...or ostriches!

This network map shows molecular interactions (yellow) associated with a congenital condition that causes heart arrhythmias and the targets for drugs that alter these interactions (red and blue).

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.

At the root tips of the mustard plant Arabidopsis thaliana (red), two proteins work together to control the uptake of water and nutrients. When the cell division-promoting protein called Short-root moves from the center of the tip outward, it triggers the production of another protein (green) that confines Short-root to the nutrient-filtering endodermis. The mechanism sheds light on how genes and proteins interact in a model organism and also could inform the engineering of plants.

This image shows collagen, a fibrous protein that's the main component of the extracellular matrix (ECM). Collagen is a strong, ropelike molecule that forms stretch-resistant fibers. The most abundant protein in our bodies, collagen accounts for about a quarter of our total protein mass. Among its many functions is giving strength to our tendons, ligaments and bones and providing scaffolding for skin wounds to heal. There are about 20 different types of collagen in our bodies, each adapted to the needs of specific tissues.

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.

Zika virus is shown in cross section at center left. On the outside, it includes envelope protein (red) and membrane protein (magenta) embedded in a lipid membrane (light purple). Inside, the RNA genome (yellow) is associated with capsid proteins (orange). The viruses are shown interacting with receptors on the cell surface (green) and are surrounded by blood plasma molecules at the top.

During development, a zebrafish embryo is transformed from a ball of cells into a recognizable body plan by sweeping convergence and extension cell movements. This process is called gastrulation. Each line in this video represents the movement of a single zebrafish embryo cell over the course of 3 hours. The video was created using time-lapse confocal microscopy. Related to image 6775.

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.

Various views of a mouse brain that was genetically modified so that subpopulations of its neurons glow. Researchers often study mice because they share many genes with people and can shed light on biological processes, development, and diseases in humans.

This video was captured using a light sheet microscope.

Related to images 6929 and 6930.

This image shows hundreds of human embryonic stem cells in various stages of differentiating into neurons. Some cells have become neurons (red), while others are still precursors of nerve cells (green). The yellow is an imaging artifact resulting when cells in both stages are on top of each other. Image and caption information courtesy of the California Institute for Regenerative Medicine.

A 20-µm thick section of mouse midbrain. The nerve cells are transparent and weren’t stained. Instead, the color is generated by interaction of white polarized light with the molecules in the cells and indicates their orientation.

The image was obtained with a polychromatic polarizing microscope that shows the polychromatic birefringent image with hue corresponding to the slow axis orientation. More information about the microscopy that produced this image can be found in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak.

Stanford University scientist Vijay Pande decided to couple the power of computers with the help of the public. He initiated a project called Folding@Home, a so-called distributed computing project in which anyone who wants to can download a screensaver that performs protein-folding calculations when a computer is not in use. Folding@Home is modeled on a similar project called SETI@Home, which is used to search for extraterrestrial intelligence.

The feeding tube, or pharynx, of a planarian worm with cilia shown in red and muscle fibers shown in green