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 .

Two mouse fibroblasts, one of the most common types of cells in mammalian connective tissue. They play a key role in wound healing and tissue repair. This image was captured using structured illumination microscopy.

This skyline of New York City was created by “printing” nanodroplets containing yeast (Saccharomyces cerevisiae) onto a large plate. Each dot is a separate yeast colony. As the colonies grew, a picture emerged, creating art. To make the different colors shown here, yeast strains were genetically engineered to produce pigments naturally made by bacteria, fungi, and sea creatures such as coral and sea anemones. Using genes from other organisms to make biological compounds paves the way toward harnessing yeast in the production of other useful molecules, from food to fuels and drugs.

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.

A nanometer-sized biosensor can detect a single deadly bacterium in tainted ground beef. How? Researchers attached nanoparticles, each packed with thousands of dye molecules, to an antibody that recognizes the microbe E. coli O157:H7. When the nanoball-antibody combo comes into contact with the E. coli bacterium, it glows. Here is the transition, a single bacterial cell glows brightly when it encounters nanoparticle-antibody biosensors, each packed with thousands of dye molecules.

An RNA molecule dynamically refolds itself as it is being synthesized. When the RNA is short, it ties itself into a “knot” (dark purple). For this domain to slip its knot, about 5 seconds into the video, another newly forming region (fuchsia) wiggles down to gain a “toehold.” About 9 seconds in, the temporarily knotted domain untangles and unwinds. Finally, at about 23 seconds, the strand starts to be reconfigured into the shape it needs to do its job in the cell.

A whole yeast (Saccharomyces cerevisiae) cell viewed by X-ray microscopy. Inside, the nucleus and a large vacuole (red) are visible.

A 360-degree view of the molecule himastatin, which was first isolated from the bacterium Streptomyces himastatinicus. Himastatin shows antibiotic activity. The researchers who created this video developed a new, more concise way to synthesize himastatin so it can be studied more easily.

More information about the research that produced this video can be found in the Science paper “Total synthesis of himastatin” by D’Angelo et al.

Related to images 6848 and 6850.

DNA doesn't leave a fossil record in stone, the way bones do. Instead, the DNA code itself holds the best evidence for organisms' genetic history. Some of the most telling evidence about genetic history comes from retroviruses, the remnants of ancient viral infections.

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.

Microtubules (magenta) and tau protein (light blue) in a cell model of tauopathy. Researchers believe that tauopathy—the aggregation of tau protein—plays a role in Alzheimer’s disease and other neurodegenerative diseases. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6889, 6890, and 6891.

Myotonic dystrophy is thought to be caused by the binding of a protein called Mbnl1 to abnormal RNA repeats. In these two images of the same muscle precursor cell, the top image shows the location of the Mbnl1 splicing factor (green) and the bottom image shows the location of RNA repeats (red) inside the cell nucleus (blue). The white arrows point to two large foci in the cell nucleus where Mbnl1 is sequestered with RNA.

These vials may look like they're filled with colored water, but they really contain nanocrystals reflecting different colors under ultraviolet light. The tiny crystals, made of semiconducting compounds, are called quantum dots. Depending on their size, the dots emit different colors that let scientists use them as a tool for detecting particular genes, proteins, and other biological molecules.

Sulfite oxidase is an enzyme that is essential for normal neurological development in children. This video shows the active site of the enzyme and its molybdenum cofactor visible as a faint ball-and-stick representation buried within the protein. The positively charged channel (blue) at the active site contains a chloride ion (green) and three water molecules (red). As the protein oscillates, one can see directly down the positively charged channel. At the bottom is the molybdenum atom of the active site (light blue) and its oxo group (red) that is transferred to sulfite to form sulfate in the catalytic reaction.

Merged fluorescent images of symmetrically (left) or asymmetrically (right) elongating HeLa cells at the end of early anaphase (magenta) and late anaphase (green). Chromosomes and cortical actin are visualized by expressing mCherry-histone H2B and Lifeact-mCherry. Scale bar, 10µm. See the PubMed abstract of this research.

Superconducting magnet for NMR research, from the February 2003 profile of Dorothee Kern in Findings.

Human cells with the gene that codes for the protein FIT2 deleted. Green indicates an endoplasmic reticulum (ER) resident protein. The lack of FIT2 affected the structure of the ER and caused the resident protein to cluster in ER membrane aggregates, seen as large, bright-green spots. Red shows where the degradation of cell parts—called autophagy—is taking place, and the nucleus is visible in blue. This image was captured using a confocal microscope. Related to image 6774.

Blood vessels at the back of the eye (retina) are used to diagnose glaucoma and diabetic eye disease. They also display characteristic changes in people with high blood pressure. In the image, the vessels appear green. It's not actually the vessels that are stained green, but rather filaments of a protein called actin that wraps around the vessels. Most of the red blood cells were replaced by fluid as the tissue was prepared for the microscope. The tiny red dots are red blood cells that remain in the vessels. The image was captured using confocal and 2-photon excitation microscopy for a project related to neurofibromatosis.

Originally from the waters of India, Nepal, and neighboring countries, zebrafish can now be found swimming in science labs (and home aquariums) throughout the world. This fish is a favorite study subject for scientists interested in how genes guide the early stages of prenatal development (including the developing fin shown here) and in the effects of environmental contamination on embryos.

In this image, green fluorescent protein (GFP) is expressed where the gene sox9b is expressed. Collagen (red) marks the fin rays, and DNA, stained with a dye called DAPI, is in blue. sox9b plays many important roles during development, including the building of the heart and brain, and is also necessary for skeletal development. At the University of Wisconsin, researchers have found that exposure to contaminants that bind the aryl-hydrocarbon receptor results in the downregulation of sox9b. Loss of sox9b severely disrupts development in zebrafish and causes a life-threatening disorder called campomelic dysplasia (CD) in humans. CD is characterized by cardiovascular, neural, and skeletal defects. By studying the roles of genes such as sox9b in zebrafish, scientists hope to better understand normal development in humans as well as how to treat developmental disorders and diseases.

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

When we walk, muscles and nerves interact in intricate ways. This simulation, which is based on data from a six-foot-tall man, shows these interactions.

T cells are white blood cells that are important in defending the body against bacteria, viruses and other pathogens. Each T cell carries proteins, called T-cell receptors, on its surface that are activated when they come in contact with an invader. This activation sets in motion a cascade of biochemical changes inside the T cell to mount a defense against the invasion. Scientists have been interested for some time what happens after a T-cell receptor is activated. One obstacle has been to study how this signaling cascade, or pathway, proceeds inside T cells.

In this image, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The image shows two key steps during the signaling process: clustering of a protein called linker for activation of T cells (LAT) (blue) and polymerization of the cytoskeleton protein actin (red). The findings show that the T-cell receptor signaling proteins self-organize into separate physical and biochemical compartments. This new system of studying molecular pathways outside the cells will enable scientists to better understand how the immune system combats microbes or other agents that cause infection.

To learn more how researchers assembled this T-cell receptor pathway, see this press release from HHMI's Marine Biological Laboratory Whitman Center. Related to video 3786.

To splice a human gene (in this case, the one for insulin) into a plasmid, scientists take the plasmid out of an E. coli bacterium, cut the plasmid with a restriction enzyme, and splice in insulin-making human DNA. The resulting hybrid plasmid can be inserted into another E. coli bacterium, where it multiplies along with the bacterium. There, it can produce large quantities of insulin. See image 2564 for an unlabeled version of this illustration. Featured in The New Genetics.

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

Groups of Staphylococcus aureus bacteria (blue) attached to a microstructured titanium surface (green) that mimics an orthopedic implant used in joint replacement. The attachment of pre-formed groups of bacteria may lead to infections because the groups can tolerate antibiotics and evade the immune system. This image was captured using a scanning electron microscope.

More information on the research that produced this image can be found in the Antibiotics paper "Free-floating aggregate and single-cell-initiated biofilms of Staphylococcus aureus" by Gupta et al.

Related to image 6804 and video 6805.

To develop a system for studying cell motility in unnatrual conditions -- a microscope slide instead of the body -- Tom Roberts and Katsuya Shimabukuro at Florida State University disassembled and reconstituted the motility parts used by worm sperm cells.

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, condensed chromosomes are clearly visible and have separated into the opposite sides of a dividing cell.

Related to images 1010, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, and 1021.

Automated crystal screening systems such as the one shown here are becoming a common feature at synchrotron and other facilities where high-throughput crystal structure determination is being carried out. These systems rapidly screen samples to identify the best candidates for further study.

Human embryonic stem cells were differentiated into cells like those found in the pancreas (blue), which give rise to insulin-producing cells (red). When implanted in mice, the stem cell-derived pancreatic cells can replace the insulin that isn't produced in type 1 diabetes. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Floral pattern emerging as two bacterial species, motile Acinetobacter baylyi and non-motile Escherichia coli (green), are grown together for 24 hours on 0.75% agar surface from a small inoculum in the center of a Petri dish.

See 6553 for a photo of this process at 48 hours on 1% agar surface.
See 6555 for another photo of this process at 48 hours on 1% agar surface.
See 6556 for a photo of this process at 72 hours on 0.5% agar surface.
See 6550 for a video of this process.

Microfluidic chips have many uses in biology labs. The one shown here was used by bioengineers to study bacteria, allowing the researchers to synchronize their fluorescing so they would blink in unison. Related to images 3266 and 3268. From a UC San Diego news release, "Researchers create living 'neon signs' composed of millions of glowing bacteria."

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3416, 3417, 3418, and 3419.

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

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.

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.

Image of Streptococcus, a type (genus) of spherical bacteria that can colonize the throat and back of the mouth. Stroptococci often occur in pairs or in chains, as shown here.

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.

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.

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 2563 for a labeled version of this illustration. Featured in The New Genetics.

The human body keeps time with a master clock called the suprachiasmatic nucleus or SCN. Situated inside the brain, it's a tiny sliver of tissue about the size of a grain of rice, located behind the eyes. It sits quite close to the optic nerve, which controls vision, and this means that the SCN "clock" can keep track of day and night. The SCN helps control sleep and maintains our circadian rhythm--the regular, 24-hour (or so) cycle of ups and downs in our bodily processes such as hormone levels, blood pressure, and sleepiness. The SCN regulates our circadian rhythm by coordinating the actions of billions of miniature "clocks" throughout the body. These aren't actually clocks, but rather are ensembles of genes inside clusters of cells that switch on and off in a regular, 24-hour (or so) cycle in our physiological day.

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.

The genetic code in DNA is transcribed into RNA, which is translated into proteins with specific sequences. During transcription, 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 2509 for an unlabeled version of this illustration.

Featured in The Structures of Life.

The cerebellum is the brain's locomotion control center. 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.

This image of a mouse cerebellum is part of a collection of such images in different colors and at different levels of magnification from the National Center for Microscopy and Imaging Research (NCMIR). Related to image 5800.

A Janus particle being used to activate a T cell, a type of immune cell. A Janus particle is a specialized microparticle with different physical properties on its surface, and this one is coated with nickel on one hemisphere and anti-CD3 antibodies (light blue) on the other. The nickel enables the Janus particle to be moved using a magnet, and the antibodies bind to the T cell and activate it. The T cell in this video was loaded with calcium-sensitive dye to visualize calcium influx, which indicates activation. The intensity of calcium influx was color coded so that warmer color indicates higher intensity. Being able to control Janus particles with simple magnets is a step toward controlling individual cells’ activities without complex magnetic devices.

More details can be found in the Angewandte Chemie paper “Remote control of T cell activation using magnetic Janus particles” by Lee et al. This video was captured using epi-fluorescence microscopy.

Related to video 6801.

Taste buds in a mouse tongue epithelium with types I, II, and III taste cells visualized by cell-type-specific fluorescent antibodies. Type II taste bud cells signal sweet, bitter, and umami tastes to the central nervous system by releasing ATP through the voltage-gated ion channel CALHM1. Researchers used a confocal microscope to capture this image, which shows all taste buds in red, type II taste buds in green, and DNA in blue.

More information about this work can be found in the Nature letter "CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes” by Taruno et. al.

Trajectories of single molecule labeled cell surface receptors. This is an example of NIH-supported research on single-cell analysis. Related to 2798 , 2799, 2800, 2802 and 2803.

A model of thymidylate synthase complementing protein from Thermotoga maritime.

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Cells are connected to one another by their cell walls, shown in blue. Stained cytoplasm (green) and membranes (magenta) show that the individual cells remain separate. This image was captured using spinning disk confocal microscopy.

Related to images 6969 and 6971.

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 complex between CCD-1 and the antibiotic cefotaxime (purple, yellow, and blue molecule). The structure revealed that CCD-1 provides extensive hydrogen bonding (shown as dotted lines) and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6766.