Irina Dementieva, a biochemist, and Youngchang Kim, a biophysicist and crystallographer, work with the first robot of its type in the U.S. to automate protein purification. The robot, which is housed in a refrigerator, is an integral part of the Midwest Structural Genomics Center's plan to automate the protein crystallography process.

Animation for the vesicular shuttle model of Golgi transport.

A typical animal cell cycle lasts roughly 24 hours, but depending on the type of cell, it can vary in length from less than 8 hours to more than a year. Most of the variability occurs in Gap1. Appears in the NIGMS booklet Inside the Cell.

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.

The cells shown here are fibroblasts, one of the most common cells in mammalian connective tissue. These particular cells were taken from a mouse embryo. Scientists used them to test the power of a new microscopy technique that offers vivid views of the inside of a cell. The DNA within the nucleus (blue), mitochondria (green), and actin filaments in the cellular skeleton (red) are clearly visible.

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

The receptor is shown bound to an antagonist, ML056.

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 video, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The video shows three key steps during the signaling process: phosphorylation of the T-cell receptor (green), 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 image 3787.

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.

This delicate, birdlike projection is an immature seed of the Arabidopsis plant. The part in blue shows the cell that gives rise to the endosperm, the tissue that nourishes the embryo. The cell is expressing only the maternal copy of a gene called MEDEA. This phenomenon, in which the activity of a gene can depend on the parent that contributed it, is called genetic imprinting. In Arabidopsis, the maternal copy of MEDEA makes a protein that keeps the paternal copy silent and reduces the size of the endosperm. In flowering plants and mammals, this sort of genetic imprinting is thought to be a way for the mother to protect herself by limiting the resources she gives to any one embryo. Featured in the May 16, 2006, issue of Biomedical Beat.

Related to image 5870.

A light microscope image of a cell 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.

Related to images 1010, 1011, 1012, 1014, 1015, 1016, 1017, 1018, 1019, and 1021.

Antibiotic resistance in microbes is a serious health concern. So researchers have turned their attention to how bacteria undo the action of some antibiotics. Here, scientists set out to find the conditions that help individual bacterial cells survive in the presence of the antibiotic rifampicin. The research team used Mycobacterium smegmatis, a more harmless relative of Mycobacterium tuberculosis, which infects the lung and other organs and causes serious disease.

In this image, genetically identical mycobacteria are growing in a miniature growth chamber called a microfluidic chamber. Using live imaging, the researchers found that individual mycobacteria will respond differently to the antibiotic, depending on the growth stage and other timing factors. The researchers used genetic tagging with green fluorescent protein to distinguish cells that can resist rifampicin and those that cannot. With this gene tag, cells tolerant of the antibiotic light up in green and those that are susceptible in violet, enabling the team to monitor the cells' responses in real time.

To learn more about how the researchers studied antibiotic resistance in mycobacteria, see this news release from Tufts University. Related to video 5752.

In plants, as in animals, stem cells can transform into a variety of different cell types. The stem cells at the growing tip of this Arabidopsis plant will soon become flowers. Arabidopsis is frequently studied by cellular and molecular biologists because it grows rapidly (its entire life cycle is only 6 weeks), produces lots of seeds, and has a genome that is easy to manipulate.

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

Three C. elegans, tiny roundworms, with a ribosomal protein glowing red and muscle fibers glowing green. Researchers used these worms to study a molecular pathway that affects aging. The ribosomal protein is involved in protein translation and may play a role in dietary restriction-induced longevity. Image created using confocal microscopy.
View single roundworm here 6581.
View closeup of roundworms here 6583.

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.

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.

Model of the catalytic portion of an enzyme, receptor-type tyrosine-protein phosphatase from humans. The enzyme consists of two identical protein subunits, shown in blue and green. The groups made up of purple and red balls represent phosphate groups, chemical groups that can influence enzyme activity. This phosphatase removes phosphate groups from the enzyme tyrosine kinase, counteracting its effects.

Scientists from Argonne National Laboratory's Advanced Photon Source (APS) display the first X-ray diffraction pattern obtained from a protein crystal using a split X-ray beam, the first of its kind at APS. The scientists shown are (from left to right): Oleg Makarov, Ruslan Sanishvili, Robert Fischetti (project manager), Sergey Stepanov, and Ward Smith.

These images show three stages of cell division in Xenopus XL177 cells, which are derived from tadpole epithelial cells. They are (from top): metaphase, anaphase and telophase. The microtubules are green and the chromosomes are blue. Related to 3443.

This image shows neonatal mouse heart cells. These cells were grown in the lab on a chip that aligns the cells in a way that mimics what is normally seen in the body. Green shows the protein N-cadherin, which indicates normal connections between cells. Red indicates the muscle protein actin, and blue indicates the cell nuclei. The work shown here was part of a study attempting to grow heart tissue in the lab to repair damage after a heart attack. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to images 3281 and 3283.

An atomic force microscopy image shows DNA folded into an intricate, computer-designed structure. Image is featured on Biomedical Beat blog post Cool Image: DNA Origami. See also related image 3689 .

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).

On the left, a cross-section slice of a rat pancreas cell captured using cryo-electron tomography (cryo-ET). On the right, a 3D, color-coded version of the image highlighting cell structures. Visible features include microtubules (neon-green rods), ribosomes (small yellow circles), and vesicles (dark-blue circles). These features are surrounded by the partially visible endoplasmic reticulum (light blue). The black line at the bottom right of the left image represents 200 nm. Related to image 6607.

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.

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.

Borrelia burgdorferi is a spirochete, a class of long, slender bacteria that typically take on a coiled shape. Infection with this bacterium causes Lyme disease.

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.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. Circadian rhythms are influenced by light and regulated by the brain’s suprachiasmatic nucleus (SCN), sometimes referred to as a master clock. Learn more in NIGMS’ circadian rhythms fact sheet. See 6614 for the Spanish version of this infographic.

Antibiotic resistance in microbes is a serious health concern. So researchers have turned their attention to how bacteria undo the action of some antibiotics. Here, scientists set out to find the conditions that help individual bacterial cells survive in the presence of the antibiotic rifampicin. The research team used Mycobacterium smegmatis, a more harmless relative of Mycobacterium tuberculosis, which infects the lung and other organs to cause serious disease.

In this video, genetically identical mycobacteria are growing in a miniature growth chamber called a microfluidic chamber. Using live imaging, the researchers found that individual mycobacteria will respond differently to the antibiotic, depending on the growth stage and other timing factors. The researchers used genetic tagging with green fluorescent protein to distinguish cells that can resist rifampicin and those that cannot. With this gene tag, cells tolerant of the antibiotic light up in green and those that are susceptible in violet, enabling the team to monitor the cells' responses in real time.

To learn more about how the researchers studied antibiotic resistance in mycobacteria, see this news release from Tufts University. Related to image 5751.

An NMR solution structure model of the transfer RNA splicing enzyme endonuclease in humans (subunit Sen15). This represents the first structure of a eukaryotic tRNA splicing endonuclease subunit.

This illustration shows vesicle traffic inside a cell. The double membrane that bounds the nucleus flows into the ribosome-studded rough endoplasmic reticulum (purple), where membrane-embedded proteins are manufactured. Proteins are processed and lipids are manufactured in the smooth endoplasmic reticulum (blue) and Golgi apparatus (green). Vesicles that fuse with the cell membrane release their contents outside the cell. The cell can also take in material from outside by having vesicles pinch off from the cell membrane.

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. Featured in the March 2006, issue of Findings in "Viral Voyages."

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.

Fat tissue from the abdomen of a genetically mosaic adult fruit fly. Genetic mosaicism means that the fly has cells with different genotypes even though it formed from a single zygote. This specific mosaicism results in accumulation of a critical fly adipokine (blue-green) within the fat tissue cells that have reduced expression a key nutrient sensing gene (in left panel). The dotted line shows the cells lacking the gene that is present and functioning in the rest of the cells. Nuclei are labelled in magenta. This image was captured using a confocal microscope and shows a maximum intensity projection of many slices.

Related to images 6982, 6984, and 6985.

A light microscope image of a cell 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 are starting to separate to form two new cells.

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

The cone cell of the eye allows you to see in color. Appears in the NIGMS booklet Inside the Cell.

This image of the human brain uses colors and shapes to show neurological differences between two people. The blurred front portion of the brain, associated with complex thought, varies most between the individuals. The blue ovals mark areas of basic function that vary relatively little. Visualizations like this one are part of a project to map complex and dynamic information about the human brain, including genes, enzymes, disease states, and anatomy. The brain maps represent collaborations between neuroscientists and experts in math, statistics, computer science, bioinformatics, imaging, and nanotechnology.

The illustration shows the capsid of human immunodeficiency virus (HIV) whose molecular features were resolved with cryo-electron microscopy (cryo-EM). On the left, the HIV capsid is "naked," a state in which it would be easily detected by and removed from cells. However, as shown on the right, when the viral capsid binds to and is covered with a host protein, called cyclophilin A (shown in red), it evades detection and enters and invades the human cell to use it to establish an infection. To learn more about how cyclophilin A helps HIV infect cells and how scientists used cryo-EM to find out the mechanism by which the HIV capsid attaches to cyclophilin A, see this news release by the University of Illinois. A study reporting these findings was published in the journal Nature Communications.

This image results from a research project to visualize which regions of the adult fruit fly (Drosophila) brain derive from each neural stem cell. First, researchers collected several thousand fruit fly larvae and fluorescently stained a random stem cell in the brain of each. The idea was to create a population of larvae in which each of the 100 or so neural stem cells was labeled at least once. When the larvae grew to adults, the researchers examined the flies’ brains using confocal microscopy.
With this technique, the part of a fly’s brain that derived from a single, labeled stem cell “lights up.” The scientists photographed each brain and digitally colorized its lit-up area. By combining thousands of such photos, they created a three-dimensional, color-coded map that shows which part of the Drosophila brain comes from each of its ~100 neural stem cells. In other words, each colored region shows which neurons are the progeny or “clones” of a single stem cell. This work established a hierarchical structure as well as nomenclature for the neurons in the Drosophila brain. Further research will relate functions to structures of the brain.

Related to image 5838 and video 5843.

This slide shows the technologies that the Joint Center for Structural Genomics developed for going from gene to structure and how the technologies have been integrated into a high-throughput pipeline, including all of the steps from target selection, parallel expression, protein purification, automated crystallization trials, automated crystal screening, structure determination, validation, and publication.

A knotted protein from an archaebacterium called Methanobacterium thermoautotrophicam. This organism breaks down waste products and produces methane gas. Protein folding theory previously held that forming a knot was beyond the ability of a protein, but this structure, determined at Argonne's Structural Biology Center, proves differently. Researchers theorize that this knot stabilizes the amino acid subunits of the protein.

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.

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

Molecular model of the struture of heme. Heme is a small, flat molecule with an iron ion (dark red) at its center. Heme is an essential component of hemoglobin, the protein in blood that carries oxygen throughout our bodies. This image first appeared in the September 2013 issue of Findings Magazine. View side view of heme here 3540.

This fluorescent microscope image shows human embryonic stem cells whose nuclei are stained green. Blue staining shows the surrounding supportive feeder cells. Image and caption information courtesy of the California Institute for Regenerative Medicine. See related image 3275.

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.

Cells in an early-stage fruit fly embryo, showing the DIAP1 protein (pink), an inhibitor of apoptosis.