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.

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 scanning electron microscope picture of a nerve ending. It has been broken open to reveal vesicles (orange and blue) containing chemicals used to pass messages in the nervous system.

This is a magnified view of an Arabidopsis thaliana leaf a few days after being exposed to the pathogen Hyaloperonospora arabidopsidis. The plant from which this leaf was taken is genetically resistant to the pathogen. The spots in blue show areas of localized cell death where infection occurred, but it did not spread. Compare this response to that shown in Image 2782. Jeff Dangl has been funded by NIGMS to study the interactions between pathogens and hosts that allow or suppress infection.

From PDB entry 3c6k, Crystal structure of human spermine synthase in complex with spermidine and 5-methylthioadenosine.

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. The image shows a side view of the structure of a protein composed of two smaller proteins, called E and M. Each E and M contributes two molecules to the overall protein structure (called a heterotetramer), which is important for assembling and holding together the viral membrane, i.e., the shell that surrounds the genetic material of the dengue virus. The dengue protein's structure has revealed some portions in the protein that might be good targets for developing medications that could be used to combat dengue virus infections. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail. You can watch a rotating view of the dengue virus surface structure in video 3748.

In many animals, the egg cell develops alongside sister cells. These sister cells are called nurse cells in the fruit fly (Drosophila melanogaster), and their job is to “nurse” an immature egg cell, or oocyte. Toward the end of oocyte development, the nurse cells transfer all their contents into the oocyte in a process called nurse cell dumping. This video captures this transfer, showing significant shape changes on the part of the nurse cells (blue), which are powered by wavelike activity of the protein myosin (red). Researchers created the video using a confocal laser scanning microscope. Related to image 6753.

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.

The nuclei stained green highlight human embryonic stem cells grown under controlled conditions in a laboratory. Blue represents the DNA of surrounding, supportive feeder cells. Image and caption information courtesy of the California Institute for Regenerative Medicine. See related image 3724.

Stereo triplet of a sea urchin embryo stained to reveal actin filaments (orange) and microtubules (blue). This image is part of a series of images: 1047, 1048, 1049, 1050 and 1051.

Telophase during mitosis: Nuclear membranes form around each of the two sets of chromosomes, the chromosomes begin to spread out, and the spindle begins to break down. 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.

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.

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

In this video, Rice University scientists used molecular modeling with a mathematical algorithm called AWSEM (for associative memory, water-mediated, structure and energy model) and structural data to analyze how a transcription factor called nuclear factor kappa B (NFkB) is removed from DNA to stop gene activation. AWSEM uses the interacting energies of their components to predict how proteins fold. At the start, the NFkB dimer (green and yellow, in the center) grips DNA (red, to the left), which activates the transcription of genes. IkB (blue, to the right), an inhibitor protein, stops transcription when it binds to NFkB and forces the dimer to twist and release its hold on DNA. The yellow domain at the bottom of IkB is the PEST domain, which binds first to NFkB. For more details about this mechanism called molecular stripping, see here.

This montage of tiny, transparent C. elegans--or roundworms--may offer insight into understanding human infertility. Researchers used fluorescent dyes to label the worm cells and watch the process of sex cell division, called meiosis, unfold as nuclei (blue) move through the tube-like gonads. Such visualization helps the scientists identify mechanisms that enable these roundworms to reproduce successfully. Because meiosis is similar in all sexually reproducing organisms, what the scientists learn could apply to humans.

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, 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.

A cancer cell with three nuclei, shown in turquoise. The abnormal number of nuclei indicates that the cell failed to go through cell division, probably more than once. Mitochondria are shown in yellow, and a protein of the cell’s cytoskeleton appears in red. This video was captured using a confocal microscope.

During embryonic development, transcription factors (proteins that regulate gene expression) govern the differentiation of cells into separate tissues and organs. Researchers at Cincinnati Children's Hospital Medical Center used mice to study the development of certain internal organs, including the liver, pancreas, duodenum (beginning part of the small intestine), gall bladder and bile ducts. They discovered that transcription factor Sox17 guides some cells to develop into liver cells and others to become part of the pancreas or biliary system (gall bladder, bile ducts and associated structures). The separation of these two distinct cell types (liver versus pancreas/biliary system) is complete by embryonic day 8.5 in mice. The transcription factors PDX1 and Hes1 are also known to be involved in embryonic development of the pancreas and biliary system. This image shows mouse cells at embryonic day 10.5. The green areas show cells that will develop into the pancreas and/or duodenum(PDX1 is labeled green). The blue area near the bottom will become the gall bladder and the connecting tubes (common duct and cystic duct) that attach the gall bladder to the liver and pancreas (Sox17 is labeled blue). The transcription factor Hes1 is labeled red. The image was not published. A similar image (different plane of the section) was published in: Sox17 Regulates Organ Lineage Segregation of Ventral Foregut Progenitor Cells Jason R. Spence, Alex W. Lange, Suh-Chin J. Lin, Klaus H. Kaestner, Andrew M. Lowy, Injune Kim, Jeffrey A. Whitsett and James M. Wells, Developmental Cell, Volume 17, Issue 1, 62-74, 21 July 2009. doi:10.1016/j.devcel.2009.05.012

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.

A number of environmental factors cause DNA mutations that can lead to cancer: toxins in cigarette smoke, sunlight and other radiation, and some viruses.

A 3D reconstruction, created using cryo-electron microscopy, of an ion channel known as the full-length serotonin receptor in complex with the antinausea drug granisetron (orange). Ion channels are proteins in cell membranes that help regulate many processes.

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.

This ribbon drawing of a protein hand drawn and colored by researcher Jane Richardson in 1981 helped originate the ribbon representation of proteins that is now ubiquitous in molecular graphics. The drawing shows the 3-dimensional structure of the protein triose phosphate isomerase. The green arrows represent the barrel of eight beta strands in this structure and the brown spirals show the protein's eight alpha helices. A black and white version of this drawing originally illustrated a review article in Advances in Protein Chemistry, volume 34, titled "Anatomy and Taxonomy of Protein Structures." The illustration was selected as Picture of The Day on the English Wikipedia for November 19, 2009. Other important and beautiful images of protein structures by Jane Richardson are available in her Wikimedia gallery.

The cryo-EM structure of human adenovirus D26 (HAdV-D26) at near atomic resolution (3.7 Å), determined in collaboration with the NRAMM facility*. In difference to archetype HAdV-C5, the HAdV-D26 is a low seroprevalent viral vector, which is being used to generate Ebola virus vaccines.

The long, stringy DNA that makes up genes is spooled within chromosomes inside the nucleus of a cell. (Note that a gene would actually be a much longer stretch of DNA than what is shown here.) See image 2539 for an unlabeled version of this illustration. Featured in The New Genetics.

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

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 2570 and 2571.

Scientists have long known that multicellular organisms use biological molecules produced by one cell and sensed by another to transmit messages that, for instance, guide proper development of organs and tissues. But it's been a puzzle as to how molecules dumped out into the fluid-filled spaces between cells can precisely home in on their targets.   Using living tissue from fruit flies, a team led by Thomas Kornberg of the University of California, San Francisco, has shown that typical cells in animals can talk to each other via long, thin cell extensions called cytonemes (Latin for "cell threads") that may span the length of 50 or 100 cells. The point of contact between a cytoneme and its target cell acts as a communications bridge between the two cells.   More information about the research behind this image can be found in a Biomedical Beat Blog posting from February 2014.

Opioid receptors on the surfaces of brain cells are involved in pleasure, pain, addiction, depression, psychosis, and other conditions. The receptors bind to both innate opioids and drugs ranging from hospital anesthetics to opium. Researchers at The Scripps Research Institute, supported by the NIGMS Protein Structure Initiative, determined the first three-dimensional structure of a human opioid receptor, a kappa-opioid receptor. In this illustration, the submicroscopic receptor structure is shown while bound to an agonist (or activator). The structure is superimposed on a poppy flower, the source of opium.

DNA encodes RNA, which encodes protein. DNA is transcribed to make messenger RNA (mRNA). The mRNA sequence (dark red strand) is complementary to the DNA sequence (blue strand). On ribosomes, transfer RNA (tRNA) reads three nucleotides at a time in mRNA to bring together the amino acids that link up to make a protein. See image 2549 for a numbered version of this illustration and 2547 for an unlabeled version. Featured in The New Genetics.

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 2570 and 2572.

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), Arp2 (green), and DAPI to visualize the nucleus (blue). Arp2, a subunit of the Arp2/3 complex, is localized at the lamellipodia leading edge of ARPC3+/+ fibroblast cells. Related to images 3329, 3330, 3331, 3332, and 3333.

The world's smallest motor, ATP synthase, generates energy for the cell. See image 2517 for an unlabeled version of this illustration. Featured in The Chemistry of Health.

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.

Kupffer cells appear in the liver during the early stages of mammalian development and stay put throughout life to protect liver cells, clean up old red blood cells, and regulate iron levels. Source article Replenishing the Liver’s Immune Protections. Posted on December 12th, 2019 by Dr. Francis Collins.

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

Inside the fertilized egg cell of a fruit fly, we see a type of myosin (related to the protein that helps muscles contract) made to glow by attaching a fluorescent protein. After fertilization, the myosin proteins are distributed relatively evenly near the surface of the embryo. The proteins temporarily vanish each time the cells' nuclei--initially buried deep in the cytoplasm--divide. When the multiplying nuclei move to the surface, they shift the myosin, producing darkened holes. The glowing myosin proteins then gather, contract, and start separating the nuclei into their own compartments.

The marine bacterium Vibrio harveyi glows when near its kind. This luminescence, which results from biochemical reactions, is part of the chemical communication used by the organisms to assess their own population size and distinguish themselves from other types of bacteria. But V. harveyi only light up when part of a large group. This communication, called quorum sensing, speaks for itself here on a lab dish, where more densely packed areas of the bacteria show up blue. Other types of bacteria use quorum sensing to release toxins, trigger disease, and evade the immune system.

Sepsis is the body’s overactive and extreme response to an infection. More than 1.7 million people get sepsis each year in the United States. Without prompt treatment, sepsis can lead to tissue damage, organ failure, and death. Many NIGMS-supported researchers are working to improve sepsis diagnosis and treatment. Learn more with our sepsis featured topic page.

See 6551 for the Spanish version of this infographic.

This wreath represents the molecular structure of a protein, Cas4, which is part of a system, known as CRISPR, that bacteria use to protect themselves against viral invaders. The green ribbons show the protein's structure, and the red balls show the location of iron and sulfur molecules important for the protein's function. Scientists harnessed Cas9, a different protein in the bacterial CRISPR system, to create a gene-editing tool known as CRISPR-Cas9. Using this tool, researchers are able to study a range of cellular processes and human diseases more easily, cheaply and precisely. In December, 2015, Science magazine recognized the CRISPR-Cas9 gene-editing tool as the "breakthrough of the year." Read more about Cas4 in the December 2015 Biomedical Beat post A Holiday-Themed Image Collection.

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.

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

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

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3414, 3415, 3416, 3417, 3418, and 3419.

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.

Shiga toxin (green) is sorted from the endosome into membrane tubules (red), which then pinch off and move to the Golgi apparatus.

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.

In the worm C. elegans, double-stranded RNA made in neurons can silence matching genes in a variety of cell types through the transport of RNA between cells. The head region of three worms that were genetically modified to express a fluorescent protein were imaged and the images were color-coded based on depth. The worm on the left lacks neuronal double-stranded RNA and thus every cell is fluorescent. In the middle worm, the expression of the fluorescent protein is silenced by neuronal double-stranded RNA and thus most cells are not fluorescent. The worm on the right lacks an enzyme that amplifies RNA for silencing. Surprisingly, the identities of the cells that depend on this enzyme for gene silencing are unpredictable. As a result, worms of identical genotype are nevertheless random mosaics for how the function of gene silencing is carried out. For more, see journal article and press release. Related to image 6532.