Developing spermatids (precursors of mature sperm cells) begin as small, round cells and mature into long-tailed, tadpole-shaped ones. In the sperm cell's head is the cell nucleus; in its tail is the power to outswim thousands of competitors to fertilize an egg. As seen in this microscopy image, fruit fly spermatids start out as groups of interconnected cells. A small lipid molecule called PIP2 helps spermatids tell their heads from their tails. Here, PIP2 (red) marks the nuclei and a cell skeleton-building protein called tubulin (green) marks the tails. When PIP2 levels are too low, some spermatids get mixed up and grow with their heads at the wrong end. Because sperm development is similar across species, studies in fruit flies could help researchers understand male infertility in humans.

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

These time series show the heart rates of four different individuals. Automakers use steel scraps to build cars, construction companies repurpose tires to lay running tracks, and now scientists are reusing previously discarded medical data to better understand our complex physiology. Through a website called PhysioNet developed in part by Beth Israel Deaconess Medical Center cardiologist Ary Goldberger, scientists can access complete physiologic recordings, such as heart rate, respiration, brain activity and gait. They then can use free software to analyze the data and find patterns in it. The patterns could ultimately help health care professionals diagnose and treat health conditions like congestive heart failure, sleeping disorders, epilepsy and walking problems. PhysioNet is supported by NIH's National Institute of Biomedical Imaging and Bioengineering as well as by NIGMS.

Cell showing overproduction of the ARTS protein (red). ARTS triggers apoptosis, as shown by the activation of caspase-3 (green) a key tool in the cell's destruction. The nucleus is shown in blue. Image is featured in October 2015 Biomedical Beat blog post Cool Images: A Halloween-Inspired Cell Collection.

Protein kinases—enzymes that add phosphate groups to molecules—are cancer chemotherapy targets because they play significant roles in almost all aspects of cell function, are tightly regulated, and contribute to the development of cancer and other diseases if any alterations to their regulation occur. Genetic abnormalities affecting the c-Abl tyrosine kinase are linked to chronic myelogenous leukemia, a cancer of immature cells in the bone marrow. In the noncancerous form of the protein, binding of a myristoyl group to the kinase domain inhibits the activity of the protein until it is needed (top left shows the inactive form, top right shows the open and active form). The cancerous variant of the protein, called Bcr-Abl, lacks this autoinhibitory myristoyl group and is continually active (bottom). ATP is shown in green bound in the active site of the kinase.

Find these in the RCSB Protein Data Bank: c-Abl tyrosine kinase and regulatory domains (PDB entry 1OPL) and F-actin binding domain (PDB entry 1ZZP).

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 model of a Geobacter sulfurreducens nanowire created from cryo-electron microscopy images. The bacterium conducts electricity through these nanowires, which are made up of protein and iron-containing molecules.

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

A growing Vibrio cholerae (cholera) biofilm. Cholera bacteria form colonies called biofilms that enable them to resist antibiotic therapy within the body and other challenges to their growth.

Each slightly curved comma shape represents an individual bacterium from assembled confocal microscopy images. Different colors show each bacterium’s position in the biofilm in relation to the surface on which the film is growing.

This image shows the uncontrolled growth of cells in squamous cell carcinoma, the second most common form of skin cancer. If caught early, squamous cell carcinoma is usually not life-threatening.

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

Student Christina Hueneke of the Midwest Center for Structural Genomics is overseeing a protein cloning robot. The robot was designed as part of an effort to exponentially increase the output of a traditional wet lab. Part of the center's goal is to cut the average cost of analyzing a protein from $200,000 to $20,000 and to slash the average time from months to days and hours.

Vibrio fischeri cells (~ 2 mm), labeled with green fluorescent protein (GFP), passing through a very narrow bottleneck in the tissues (red) of the Hawaiian bobtail squid, Euprymna scolopes, on the way to the crypts where the symbiont population resides. This image was taken using a confocal fluorescence microscope.

This photograph shows a magnified view of a Drosophila melanogaster pupa in cross section. Compare this normal pupa to one that lacks an important receptor, shown in image 2759.

Researchers use cluster analysis to study protein shape and function. Each green circle represents one potential shape of the protein mitoNEET. The longer the blue line between two circles, the greater the differences between the shapes. Most shapes are similar; they fall into three clusters that are represented by the three images of the protein. From a Rice University news release. Graduate student Elizabeth Baxter and Patricia Jennings, professor of chemistry and biochemistry at UCSD, collaborated with José Onuchic, a physicist at Rice University, on this work.

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

A cell in anaphase during mitosis: Chromosomes separate into two genetically identical groups and move to opposite ends of the spindle. Mitosis is responsible for growth and development, as well as for replacing injured or worn out cells throughout the body. For simplicity, mitosis is illustrated here with only six chromosomes.

By mixing fluorescent dyes like an artist mixes paints, scientists are able to color code individual chromosomes. The technique, abbreviated multicolor-FISH, allows researchers to visualize genetic abnormalities often linked to disease. In this image, "painted" chromosomes from a person with a hereditary disease called Werner Syndrome show where a piece of one chromosome has fused to another (see the gold-tipped maroon chromosome in the center). As reported by molecular biologist Jan Karlseder of the Salk Institute for Biological Studies, such damage is typical among people with this rare syndrome.

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.

This image shows the hierarchical ontology of genes, cellular components and processes derived from large genomic datasets. From Dutkowski et al. A gene ontology inferred from molecular networks Nat Biotechnol. 2013 Jan;31(1):38-45. Related to 3436.

Both instruments shown were developed by CellFree Sciences of Yokohama, Japan. The instrument on the left, the GeneDecoder 1000, can generate 384 proteins from their corresponding genes, or gene fragments, overnight. It is used to screen for properties such as level of protein production and degree of solubility. The instrument on the right, the Protemist Protein Synthesizer, is used to generate the larger amounts of protein needed for protein structure determinations.

This video 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 images 5838 and 5868.

Pigment cells are cells that give skin its color. In fishes and amphibians, like frogs and salamanders, pigment cells are responsible for the characteristic skin patterns that help these organisms to blend into their surroundings or attract mates. The pigment cells are derived from neural crest cells, which are cells originating from the neural tube in the early embryo. This image shows pigment cells in the fin of pearl danio, a close relative of the popular laboratory animal zebrafish. Investigating pigment cell formation and migration in animals helps answer important fundamental questions about the factors that control pigmentation in the skin of animals, including humans. Related to images 5754, 5755, 5756 and 5758.

Scanning electron micrograph of just-divided HeLa cells. Zeiss Merlin HR-SEM. See related images 3519, 3520, 3521, 3522.

RNA incorporated into the CRISPR surveillance complex is positioned to scan across foreign DNA. Cryo-EM density from a 3Å reconstruction is shown as a yellow mesh.

Serum albumin (SA) is the most abundant protein in the blood plasma of mammals. SA has a characteristic heart-shape structure and is a highly versatile protein. It helps maintain normal water levels in our tissues and carries almost half of all calcium ions in human blood. SA also transports some hormones, nutrients and metals throughout the bloodstream. Despite being very similar to our own SA, those from other animals can cause some mild allergies in people. Therefore, some scientists study SAs from humans and other mammals to learn more about what subtle structural or other differences cause immune responses in the body.

Related to entries 3744 and 3745.

Influenza (flu) virus proteins in the act of self-replication. Viral nucleoprotein (blue) encapsidates [encapsulates] the RNA genome (green). The influenza virus polymerase (orange) reads and copies the RNA genome. In the background is an image of influenza virus ribonucleoprotein complexes observed using cryo-electron microscopy. This image is from a November 2012 News Release.

The three fibers of the cytoskeleton--microtubules in blue, intermediate filaments in red, and actin in green--play countless roles in the cell.

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.

This video shows the structure of the pore-forming protein VDAC-1 from humans. This molecule mediates the flow of products needed for metabolism--in particular the export of ATP--across the outer membrane of mitochondria, the power plants for eukaryotic cells. VDAC-1 is involved in metabolism and the self-destruction of cells--two biological processes central to health.

Related to videos 2571 and 2572.

Anaphase is the critical step during mitosis when sister chromosomes are disjoined and directed to opposite spindle poles, ensuring equal distribution of the genome during cell division. In this image, one pair of sister chromosomes at the top was lost and failed to divide after chemical inhibition of polo-like kinase 1. This image depicts chromosomes (blue) separating away from the spindle mid-zone (red). Kinetochores (green) highlight impaired movement of some chromosomes away from the mid-zone or the failure of sister chromatid separation (top). Scientists are interested in detailing the signaling events that are disrupted to produce this effect. The 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. The research that led to this image was funded by NIGMS.

Related to image 5765.

NIGMS-funded researchers led by Roger Kornberg solved the structure of RNA polymerase II. This is the enzyme in mammalian cells that catalyzes the transcription of DNA into messenger RNA, the molecule that in turn dictates the order of amino acids in proteins. For his work on the mechanisms of mammalian transcription, Kornberg received the Nobel Prize in Chemistry in 2006.

The molecules that glow blue in these cultured cells prevent the expression of the mutant proteins that cause Huntington's disease. Biochemist David Corey and others at UT Southwestern Medical Center designed the molecules to specifically target the genetic repeats that code for harmful proteins in people with Huntington's disese. People with Huntington's disease and similar neurodegenerative disorders often have extra copies of a gene segment. Moving from cell cultures to animals will help researchers further explore the potential of their specially crafted molecule to treat brain disorders. In addition to NIGMS, NIH's National Institute of Neurological Disorders and Stroke and National Institute of Biomedical Imaging and Bioengineering also funded this work.

Jon Lorsch at his swearing in as NIGMS director in August 2013. Also shown are Francis Collins, NIH Director, and Judith Greenberg, former NIGMS Acting Director.

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.

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) and DAPI to visualize the nucleus (blue). ARPC3+/+ fibroblast cells with lamellipodia leading edge. Related to images 3328, 3329, 3330, 3331, and 3333.

Atomic model of the membrane region of the mitochondrial ATP synthase built into a cryo-EM map at 3.6 Å resolution. ATP synthase is the primary producer of ATP in aerobic cells. Drugs that inhibit the bacterial ATP synthase, but not the human mitochondrial enzyme, can serve as antibiotics. This therapeutic approach was successfully demonstrated with the bedaquiline, an ATP synthase inhibitor now used in the treatment of extensively drug resistant tuberculosis.

More information about this structure can be found in the Science paper ”Atomic model for the dimeric F0 region of mitochondrial ATP synthase” by Guo et. al.

Like a pulsing blue shower, E. coli cells flash in synchrony. Genes inserted into each cell turn a fluorescent protein on and off at regular intervals. When enough cells grow in the colony, a phenomenon called quorum sensing allows them to switch from blinking independently to blinking in unison. Researchers can watch waves of light propagate across the colony. Adjusting the temperature, chemical composition or other conditions can change the frequency and amplitude of the waves. Because the blinks react to subtle changes in the environment, synchronized oscillators like this one could one day allow biologists to build cellular sensors that detect pollutants or help deliver drugs.

Scientists in Scotland were the first to clone an animal, this sheep named Dolly. She later gave birth to Bonnie, the lamb next to her.

Video of high-resolution confocal images depicting vimentin immunofluorescence (green) and nuclei (blue) at the edge of a quail embryo yolk. These images were obtained as part of a study to understand cell migration in embryos. An NIGMS grant to Professor Garcia was used to purchase the confocal microscope that collected these images. Related to images 2807 and 2808.

Model of an enzyme, dUTP pyrophosphatase, from Mycobacterium tuberculosis. Drugs targeted to this enzyme might inhibit the replication of the bacterium that causes most cases of tuberculosis.

Mycobacterium tuberculosis, the bacterium that causes tuberculosis, has infected one-quarter of the world's population and causes more than one million deaths each year, according to the World Health Organization.

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.

Cultured hippocampal neurons grown on a substrate of glial cells (astrocytes). The glial cells form the pink/brown underlayment in this image. The tan threads are the neurons. The round tan balls are synapses, the points where neurons meet and communicate with each other. The cover slip underlying the cells is green. Neurons in culture can be used to study synaptic plasticity, activity-dependent protein turnover, and other topics in neuroscience.

A section of mouse colon with gut bacteria (center, in green) residing within a protective pocket. Understanding how microorganisms colonize the gut could help devise ways to correct for abnormal changes in bacterial communities that are associated with disorders like inflammatory bowel disease.

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

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.

Researchers used fluorescence in situ hybridization (FISH) to confirm the presence of long range DNA-DNA interactions in mouse embryonic stem cells. Here, two loci labeled in green (Oct4) and red that are 13 Mb apart on linear DNA are frequently found to be in close proximity. DNA-DNA colocalizations like this are thought to both reflect and contribute to cell type specific gene expression programs.

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.

Microscopy image of tongue. One in a series of two, see image 5811

These induced pluripotent stem cells (iPS cells) were derived from a woman's skin. Blue show nuclei. Green show a protein found in iPS cells but not in skin cells (NANOG). The red dots show the inactivated X chromosome in each cell. These cells can develop into a variety of cell types. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to image 3278.