The 3D single-molecule super-resolution reconstruction of the entire nuclear lamina in a HeLa cell was acquired using the TILT3D platform. TILT3D combines a tilted light sheet with point-spread function (PSF) engineering to provide a flexible imaging platform for 3D single-molecule super-resolution imaging in mammalian cells.
See 6573 for 3 separate views of this structure.

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.

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.

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool. This is the fifthframe in a series of five. 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). For an explanation and overview of the CRISPR-Cas9 system, see the NIGMS Biomedical Beat blog entry, Field Focus: Precision Gene Editing with CRISPR and the iBiology video, Genome Engineering with CRISPR-Cas9: Birth of a Breakthrough Technology.

A Trigonium diatom imaged by a quantitative orientation-independent differential interference contrast (OI-DIC) microscope. Diatoms are single-celled photosynthetic algae with mineralized cell walls that contain silica and provide protection and support. These organisms form an important part of the plankton at the base of the marine and freshwater food chains. The width of this image is 90 μm.

More information about the microscopy that produced this image can be found in the Journal of Microscopy paper “An Orientation-Independent DIC Microscope Allows High Resolution Imaging of Epithelial Cell Migration and Wound Healing in a Cnidarian Model” by Malamy and Shribak.

Hydra magnipapillata is an invertebrate animal used as a model organism to study developmental questions, for example the formation of the body axis.

The body uses a variety of ion channels to transport small molecules across cell membranes.

Yeast cells that abnormally accumulate cell wall material (blue) at their ends and, when preparing to divide, in their middles. This image was captured using wide-field microscopy with deconvolution.

Related to images 6791, 6792, 6793, 6794, 6798, and videos 6795 and 6796.

Cell-like compartments spontaneously emerge from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Video created using epifluorescence microscopy.

For more photos of cell-like compartments from frog eggs view: 6584, 6585, 6586, 6591, 6592, and 6593.

For videos of cell-like compartments from frog eggs view: 6588, 6589, and 6590.

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.

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. Cell nuclei are in blue. Red and orange mark hair follicle stem cells (hair follicle stem cells activate to cause hair regrowth, which indicates healing). See more information in the article in Science.

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.

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.

Glide across an icy canyon, where you see smiling snowmen and waddling penguins. Toss a snowball, hear it smash against an igloo, and then watch it explode in bright colors. Psychologists David Patterson and Hunter Hoffman of the University of Washington in Seattle developed this virtual "Snow World" to test whether immersing someone in a pretend reality could ease pain during burn treatment and other medical procedures. They found that people fully engaged in the virtual reality experience reported 60 percent less pain. The technology offers a promising way to manage pain.

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

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.

Ribbon diagram showing the structure of Ribonuclease P with tRNA.

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.

Living primary mouse embryonic fibroblasts. Mitochondria (green) stained with the mitochondrial membrane potential indicator, rhodamine 123. Nuclei (blue) are stained with DAPI. Caption from a November 26, 2012 news release from U Penn (Penn Medicine).

When a molecule arrives at a cell's outer membrane, the membrane creates a pouch around the molecule that protrudes inward. Directed by a protein called dynamin, the pouch then gets pinched off to form a vesicle that carries the molecule to the right place inside the cell. To better understand how dynamin performs its vital pouch-pinching role, researchers determined its structure. Based on the structure, they proposed that a dynamin "collar" at the pouch's base twists ever tighter until the vesicle pops free. Because cells absorb many drugs through vesicles, the discovery could lead to new drug delivery methods.

Staphylococcus aureus bacteria (green) grouping together upon contact with synovial fluid—a viscous substance found in joints. The formation of groups can help protect the bacteria from immune system defenses and from antibiotics, increasing the likelihood of an infection. This video is a 1-hour time lapse and was captured using a confocal laser scanning microscope.

More information about the research that produced this video can be found in the Journal of Bacteriology paper "In Vitro Staphylococcal Aggregate Morphology and Protection from Antibiotics Are Dependent on Distinct Mechanisms Arising from Postsurgical Joint Components and Fluid Motion" by Staats et al.

Related to images 6803 and 6804.

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

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

Two models for how material passes through the Golgi apparatus: the vesicular shuttle model and the cisternae maturation model.

Gene transcription is a process by which information encoded in DNA is transcribed into RNA. It's essential for all life and requires the activity of proteins, called transcription factors, that detect where in a DNA strand transcription should start. In eukaryotes (i.e., those that have a nucleus and mitochondria), a protein complex comprising 14 different proteins is responsible for sniffing out transcription start sites and starting the process. This complex represents the core machinery to which an enzyme, named RNA polymerase, can bind to and read the DNA and transcribe it to RNA. Scientists have used cryo-electron microscopy (cryo-EM) to visualize the TFIID-RNA polymerase-DNA complex in unprecedented detail. This animation shows the different TFIID components as they contact DNA and recruit the RNA polymerase for gene transcription.

To learn more about the research that has shed new light on gene transcription, see this news release from Berkeley Lab.

Related to image 3766.

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.

Cdc42, a member of the Rho family of small guanosine triphosphatase (GTPase) proteins, regulates multiple cell functions, including motility, proliferation, apoptosis, and cell morphology. In order to fulfill these diverse roles, the timing and location of Cdc42 activation must be tightly controlled. Klaus Hahn and his research group use special dyes designed to report protein conformational changes and interactions, here in living neutrophil cells. Warmer colors in this image indicate higher levels of activation. Cdc42 looks to be activated at cell protrusions.

Related to images 2451, 2452, and 2454.

Disassembly of vasculature in kdr:GFP frogs following addition of 250 µM TBZ. Related to images 3404 and 3505.

This image shows Q fever bacteria (yellow), which infect cows, sheep, and goats around the world and can infect humans, as well. When caught early, Q fever can be cured with antibiotics. A small fraction of people can develop a more serious, chronic form of the disease.

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

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

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.

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

Just 22 hours after fertilization, this zebrafish embryo is already taking shape. By 36 hours, all of the major organs will have started to form. The zebrafish's rapid growth and see-through embryo make it ideal for scientists studying how organs develop.

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 bovine milk alpha-lactalbumin protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

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.

This normal human skin cell was treated with a growth factor that triggered the formation of specialized protein structures that enable the cell to move. We depend on cell movement for such basic functions as wound healing and launching an immune response.

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

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.

Skins cells were reprogrammed into heart muscle cells. The cells highlighted in green are remaining skin cells. Red indicates a protein that is unique to heart muscle. The technique used to reprogram the skin cells into heart cells could one day be used to mend heart muscle damaged by disease or heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine.

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.

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.

This illustration of an epoxide-opening cascade promoted by water emulates the proposed biosynthesis of some of the Red Tide toxins.

For thousands of years, Chinese herbalists have treated malaria using Chang Shan, a root extract from a type of hydrangea that grows in Tibet and Nepal. Recent studies have suggested Chang Shan can also reduce scar formation, treat multiple sclerosis and even slow cancer progression.

Fruit fly sperm cells glow bright green when they express the gene for green fluorescent protein (GFP).

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.

Structure of the bacterial antitoxin protein GhoS. GhoS inhibits the production of a bacterial toxin, GhoT, which can contribute to antibiotic resistance. GhoS is the first known bacterial antitoxin that works by cleaving the messenger RNA that carries the instructions for making the toxin. More information can be found in the paper: Wang X, Lord DM, Cheng HY, Osbourne DO, Hong SH, Sanchez-Torres V, Quiroga C, Zheng K, Herrmann T, Peti W, Benedik MJ, Page R, Wood TK. A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol. 2012 Oct;8(10):855-61. Related to 3428.

This illustration represents the early life of a protein—specifically, apomyoglobin—as it is synthesized by a ribosome and emerges from the ribosomal tunnel, which contains the newly formed protein's conformation. The synthesis occurs in the complex swirl of the cell medium, filled with interactions among many molecules. Researchers in Silvia Cavagnero's laboratory are studying the structure and dynamics of newly made proteins and polypeptides using spectroscopic and biochemical techniques.

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.

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.

How far and fast an infectious disease spreads across a community depends on many factors, including transportation. These U.S. maps, developed as part of an international study to simulate and analyze disease spread, chart daily commuting patterns. They show where commuters live (top) and where they travel for work (bottom). Green represents the fewest number of people whereas orange, brown, and white depict the most. Such information enables researchers and policymakers to visualize how an outbreak in one area can spread quickly across a geographic region.

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.