The human skin cells pictured contain genetic modifications that make them pluripotent, essentially equivalent to embryonic stem cells. A scientific team from the University of Wisconsin-Madison including researchers Junying Yu, James Thomson, and their colleagues produced the transformation by introducing a set of four genes into human fibroblasts, skin cells that are easy to obtain and grow in culture.

On the left, the boundary of a breast tumor (yellow) attaches to collagen fibers that are closest to it (green) using DDR2. On the right, a tumor without DDR2 remains disconnected from the collagen.

A blue laser beam turns on a protein that helps this human cancer cell move. Responding to the stimulus, the protein, called Rac1, first creates ruffles at the edge of the cell. Then it stretches the cell forward, following the light like a horse trotting after a carrot on a stick. This new light-based approach can turn Rac1 (and potentially many other proteins) on and off at exact times and places in living cells. By manipulating a protein that controls movement, the technique also offers a new tool to study embryonic development, nerve regeneration and cancer.

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

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

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.

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool. The CRISPR system has two components joined together: a finely tuned targeting device (a small strand of RNA programmed to look for a specific DNA sequence) and a strong cutting device (an enzyme called Cas9 that can cut through a double strand of DNA). In this frame (3 of 4), the Cas9 enzyme cuts both strands of the DNA.

For an explanation and overview of the CRISPR-Cas9 system, see the iBiology video, and find the full CRIPSR illustration here.

A microtubule, part of the cell's skeleton, builds and deconstructs.

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.

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.

These neurons are derived from mouse embryonic stem cells. Red shows cells making a protein called TH that is characteristic of the neurons that degenerate in Parkinson's disease. Green indicates a protein that's found in all neurons. Blue indicates the nuclei of all cells. Studying dopaminergic neurons can help researchers understand the origins of Parkinson's disease and could be used to screen potential new drugs. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to images 3270 and 3285.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. This image shows how luciferase-based imaging could be used to visualize the heart for regeneration studies (left), or label all tissues for stem cell transplantation (right).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.

It's probably most people's least favorite activity, but we still need to do it--take out our trash. Otherwise our homes will get cluttered and smelly, and eventually, we'll get sick. The same is true for our cells: garbage disposal is an ongoing and essential activity, and our cells have a dedicated waste-management system that helps keep them clean and neat. One major waste-removal agent in the cell is the lysosome. Lysosomes are small structures, called organelles, and help the body to dispose of proteins and other molecules that have become damaged or worn out.

This image shows a massive accumulation of lysosomes (visualized with LAMP1 immunofluorescence, in purple) within nerve cells that surround amyloid plaques (visualized with beta-amyloid immunofluorescence, in light blue) in a mouse model of Alzheimer's disease. Scientists have linked accumulation of lysosomes around amyloid plaques to impaired waste disposal in nerve cells, ultimately resulting in cell death.

Image showing that the edge zone (top of image) of the quail embryo shows no proliferating cells (cyan), unlike the interior zone (bottom of image). Non-proliferating cell nuclei are labeled green. This image was obtained as part of a study to understand cell migration in embryos. More specifically, cell proliferation at the edge of the embryo was studied by examining the cellular uptake of a chemical compound called BrDU, which incorporates into the DNA during the S-phase of the cell cycle. Here, the cells that are positive for BrDU uptake are labeled in cyan, while other non-proliferating cell nuclei are labeled green. Notice that the vast majority of BrDU+ cells are located far away from the edge, indicating that edge cells are mostly non-proliferating. An NIGMS grant to Professor Garcia was used to purchase the confocal microscope that collected this image. Related to image 2807 and video 2809.

Automated methods using micromachined silicon are used at the Northeast Collaboratory for Structural Genomics to mount protein crystals for X-ray crystallography.

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.

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 2513 and 2515 for other versions of this illustration. Featured in The Structures of Life.

It has been said that gastrulation is the most important event in a person's life. This part of early embryonic development transforms a simple ball of cells and begins to define cell fate and the body axis. In a study published in Science magazine, NIGMS grantee Bob Goldstein and his research group studied how contractions of actomyosin filaments in C. elegans and Drosophila embryos lead to dramatic rearrangements of cell and embryonic structure. In these images, myosin (green) and plasma membrane (red) are highlighted at four timepoints in gastrulation in the roundworm C. elegans. The blue highlights in the top three frames show how cells are internalized, and the site of closure around the involuting cells is marked with an arrow in the last frame. See related image 3297.

The 46 human chromosomes are shown in blue, with the telomeres appearing as white pinpoints. The DNA has already been copied, so each chromosome is actually made up of two identical lengths of DNA, each with its own two telomeres.

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

The green spots in this image are clumps of protein inside yeast cells that are deficient in both zinc and a protein called Tsa1 that prevents clumping. Protein clumping plays a role in many diseases, including Parkinson's and Alzheimer's, where proteins clump together in the brain. Zinc deficiency within a cell can cause proteins to mis-fold and eventually clump together. Normally, in yeast, Tsa1 codes for so-called "chaperone proteins" which help proteins in stressed cells, such as those with a zinc deficiency, fold correctly. The research behind this image was published in 2013 in the Journal of Biological Chemistry.

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.

Three-dimensional reconstruction of a tubular matrix in a thin section of the peripheral endoplasmic reticulum between the plasma membranes of the cell.
The endoplasmic reticulum (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.
Shown here are super-resolution microscopic images of the peripheral ER showing the structure of an ER tubular matrix between the plasma membranes of the cell. See image 5857 for a more detailed view of the area outlined in white in this image. For another view of the ER tubular matrix see image 5855

NIGMS staff are located in the Natcher Building on the NIH campus.

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.

NIGMS staff are located in the Natcher Building on the NIH campus.

Nerve cells have long, invisibly thin fibers that carry electrical impulses throughout the body. Some of these fibers extend about 3 feet from the spinal cord to the toes.

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 structure of a gene-regulating zinc finger protein bound to DNA.

During mitosis, spindle microtubules (red) attach to chromosome pairs (blue), directing them to the spindle equator. This midline alignment is critical for equal distribution of chromosomes in the dividing cell. Scientists are interested in how the protein kinase Plk1 (green) regulates this activity in human cells. 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. Related to image 5766.

The research that led to this image was funded by NIGMS.

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.

These induced pluripotent stem cells (iPS cells) were derived from a woman's skin. Green and red indicate proteins found in reprogrammed cells but not in skin cells (TRA1-62 and NANOG). These cells can then develop into different cell types. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to image 3279.

Dictyostelium discoideum is a microscopic amoeba. A group of 100,000 form a mound as big as a grain of sand. Featured in The New Genetics.

Each morning, the nocturnal Hawaiian bobtail squid, Euprymna scolopes, hides from predators by digging into the sand. At dusk, it leaves the sand again to hunt.

Related to image 7010 and 7011.

These colorful, computer-generated ribbons show the backbone of a molecule that glows a fluorescent red. The molecule, called mStrawberry, was created by chemists based on a protein found in the ruddy lips of a coral. Scientists use the synthetic molecule and other "fruity" ones like it as a dye to mark and study cell structures.

Mitochondria are the powerhouses of the cells, generating the energy the cells need to do their tasks and to stay alive. Researchers have studied mitochondria for some time because when these cell organelles don't work as well as they should, several diseases develop. In this photograph of cow cells taken with a microscope, the mitochondria were stained in bright yellow to visualize them in the cell. The large blue dots are the cell nuclei and the gray web is the cytoskeleton of the cells.

Watch a cell ripple toward a beam of light that turns on a movement-related protein.

Actin is an essential protein in a cell's skeleton (cytoskeleton). It forms a dense network of thin filaments in the cell. Here, researchers have used a technique called stochastic optical reconstruction microscopy (STORM) to visualize the actin network in a cell in three dimensions. The actin strands were labeled with a dye called Alexa Fluor 647-phalloidin.  This image appears in a study published by Nature Methods, which reports how researchers use STORM to visualize the cytoskeleton.

On the left, a cross-section slice of a rat pancreas cell captured using cryo-electron tomography (cryo-ET). On the right, a color-coded, 3D version of the image highlighting cell structures. Visible features include insulin vesicles (purple rings), insulin crystals (gray circles), microtubules (green rods), ribosomes (small yellow circles). The black line at the bottom right of the left image represents 200 nm. Related to image 6608.

Two adult fruit flies (Drosophila)

Rendering of the surface of an endothelial cell; membrane curvature is color coded. This is an example of NIH-supported research on single-cell analysis. Related to 2798 , 2799, 357, 2801, and 2802.

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.

A study published in March 2012 used cryo-electron microscopy to determine the structure of the DNA replication origin recognition complex (ORC), a semi-circular, protein complex (yellow) that recognizes and binds DNA to start the replication process. The ORC appears to wrap around and bend approximately 70 base pairs of double stranded DNA (red and blue). Also shown is the protein Cdc6 (green), which is also involved in the initiation of DNA replication. Related to video 3307 that shows the structure from different angles. From a Brookhaven National Laboratory news release, "Study Reveals How Protein Machinery Binds and Wraps DNA to Start Replication."

Related to image 5870.

Multiple actin filaments (magenta) are organized around a dynamin helical polymer (rainbow colored) in this model derived from cryo-electron tomography. By bundling actin, dynamin increases the strength of a cell’s skeleton and plays a role in cell-cell fusion, a process involved in conception, development, and regeneration.

Myelinated axons in a rat spinal root. Myelin is a type of fat that forms a sheath around and thus insulates the axon to protect it from losing the electrical current needed to transmit signals along the axon. The axoplasm inside the axon is shown in pink. Related to 3397.

Ribonucleic acid (RNA) has a sugar-phosphate backbone and the bases adenine (A), cytosine (C), guanine (G), and uracil (U). See image 2555 for a labeled version of this illustration. Featured in The New Genetics.

A three-dimensional representation of the structure of E2, a key antigen protein involved with hepatitis C virus infection.

La sepsis o septicemia es la respuesta fulminante y extrema del cuerpo a una infección. En los Estados Unidos, más de 1.7 millones de personas contraen sepsis cada año. Sin un tratamiento rápido, la sepsis puede provocar daño de los tejidos, insuficiencia orgánica y muerte. El NIGMS apoya a muchos investigadores en su trabajo para mejorar el diagnóstico y el tratamiento de la sepsis.

Vea 6536 para la versión en inglés de esta infografía.

Colorized scanning electron micrographs progressively zoom in on the eye of a crab larva. In the higher-resolution frames, bacteria are visible on the eye.