The receptor is shown bound to an antagonist, compound-24

What looks a little like distant planets with some mysterious surface features are actually assemblies of proteins normally found in the cell's nucleolus, a small but very important protein complex located in the cell's nucleus. It forms on the chromosomes at the location where the genes for the RNAs are that make up the structure of the ribosome, the indispensable cellular machine that makes proteins from messenger RNAs.

However, how the nucleolus grows and maintains its structure has puzzled scientists for some time. It turns out that even though it looks like a simple liquid blob, it's rather well-organized, consisting of three distinct layers: the fibrillar center, where the RNA polymerase is active; the dense fibrillar component, which is enriched in the protein fibrillarin; and the granular component, which contains a protein called nucleophosmin. Researchers have now discovered that this multilayer structure of the nucleolus arises from differences in how the proteins in each compartment mix with water and with each other. These differences let the proteins readily separate from each other into the three nucleolus compartments.

This photo of nucleolus proteins in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows each of the nucleolus compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue). The researchers have found that these compartments spontaneously fuse with each other on encounter without mixing with the other compartments.

For more details on this research, see this press release from Princeton. Related to video 3789, video 3791 and image 3793.

Superresolution microscopy work on endoplasmic reticulum (ER) in the peripheral areas of the cell showing details of the structure and arrangement in a complex web of tubes.
The 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. The ER has a flexible structure to allow it to accomplish these tasks by changing shape as conditions in the cell change. Shown here an image created by super-resolution microscopy of the ER in the peripheral areas of the cell showing details of the structure and the arrangements in a complex web of tubes. Related to images 5856 and 5857.

Crystal structure of a protein with unknown function from Xanthomonas campestris, a plant pathogen. Eight copies of the protein crystallized to form a ring. Chosen as the December 2007 Protein Structure Initiative Structure of the Month.

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.

Actin (purple), microtubules (yellow), and nuclei (green) are labeled in these cells by immunofluorescence. This image won first place in the Nikon 2003 Small World photo competition.

These neural precursor cells were derived from human embryonic stem cells. The neural cell bodies are stained red, and the nuclei are blue. Image and caption information courtesy of the California Institute for Regenerative Medicine.

Of the three muscle fibers shown here, the one on the right and the one on the left are normal. The middle fiber is deficient a large protein called nebulin (blue). Nebulin plays a number of roles in the structure and function of muscles, and its absence is associated with certain neuromuscular disorders.

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

This animation shows atoms of the HIV capsid, the shell that encloses the virus's genetic material. Scientists determined the exact structure of the capsid using a variety of imaging techniques and analyses. They then entered this data into a supercomputer to produce this image. Related to image 3477.

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.

Nodes of Ranvier are short gaps in the myelin sheath surrounding myelinated nerve cells (axons). Myelin insulates axons, and the node of Ranvier is where the axon is exposed to the extracellular environment, allowing for the transmission of action potentials at these nodes via ion flows between the inside and outside of the axon. The image shows a cross-section through the node, with the surrounding extracellular matrix encasing and supporting the axon shown in cyan.

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

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. See more information in the article in Science.

Related to images 3498 and 3500.

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.

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

Jellyfish are especially good models for studying the evolution of embryonic tissue layers. Despite being primitive, jellyfish have a nervous system (stained green here) and musculature (red). Cell nuclei are stained blue. By studying how tissues are distributed in this simple organism, scientists can learn about the evolution of the shapes and features of diverse animals.

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

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.

Cells progress through a cycle that consists of phases for growth (G1, S, and G2) and division (M). Cells become quiescent when they exit this cycle (G0). See image 2498 for an unlabeled version of this illustration.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to images 3413, 3414, 3415, 3416, 3417, and 3419.

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 2542 for a labeled version of this illustration. Featured in The New Genetics.

The receptor is shown bound to an inverse agonist, doxepin.

Image showing rhabdomeres (red), the light-sensitive structures in the fruit fly retina, and rhodopsin-4 (blue), a light-sensing molecule.

This image is featured on the poster for Dr. Rommie Amaro's 2017 Stetten Lecture. It depicts a detailed physical model of an influenza virus, incorporating information from several structural data sources. The small molecules around the virus are sialic acid molecules. The virus binds to and cleaves sialic acid as it enters and exits host cells. Researchers are building these highly detailed molecular scale models of different biomedical systems and then “bringing them to life” with physics-based methods, either molecular or Brownian dynamics simulations, to understand the structural dynamics of the systems and their complex interactions with drug or substrate molecules.

The chemical structure of the morphine molecule

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

If a picture is worth a thousand words, what's a movie worth? For researchers studying cell migration, a "documentary" of fruit fly cells (bright green) traversing an egg chamber could answer longstanding questions about cell movement. Historically, researchers have been unable to watch this cell migration unfold in living ovarian tissue in real time. But by developing a culture medium that allows fly eggs to survive outside their ovarian homes, scientists can observe the nuances of cell migration as it happens. Such details may shed light on how immune cells move to a wound and why cancer cells spread to other sites. See 3594 for still image.

Collecting and transporting cellular waste and sorting it into recylable and nonrecylable pieces is a complex business in the cell. One key player in that process is the endosome, which helps collect, sort and transport worn-out or leftover proteins with the help of a protein assembly called the endosomal sorting complexes for transport (or ESCRT for short). These complexes help package proteins marked for breakdown into intralumenal vesicles, which, in turn, are enclosed in multivesicular bodies for transport to the places where the proteins are recycled or dumped. In this image, two multivesicular bodies (with yellow membranes) contain tiny intralumenal vesicles (with a diameter of only 25 nanometers; shown in red) adjacent to the cell's vacuole (in orange).

Scientists working with baker's yeast (Saccharomyces cerevisiae) study the budding inward of the limiting membrane (green lines on top of the yellow lines) into the intralumenal vesicles. This tomogram was shot with a Tecnai F-20 high-energy electron microscope, at 29,000x magnification, with a 0.7-nm pixel, ~4-nm resolution.

To learn more about endosomes, see the Biomedical Beat blog post The Cell’s Mailroom. Related to a microscopy photograph 5768 that was used to generate this illustration and a zoomed-in version 5767 of this illustration.

This image shows an abnormal, tetrapolar mitosis. Chromosomes are highlighted pink. The cells shown are S3 tissue cultured cells from Xenopus laevis, African clawed frog.

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.

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.

Cell mopping up.

Gene transcription is a process by which the genetic 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, called TFIID, 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. In this illustration, TFIID (blue) contacts the DNA and recruits the RNA polymerase (gray) for gene transcription. The start of the transcribed gene is shown with a flash of light. To learn more about the research that has shed new light on gene transcription, see this news release from Berkeley Lab. Related to video 5730.

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.

Details about the basic biology and chemistry of the ingredients that produce bioluminescence are allowing scientists to harness it as an imaging tool. Credit: Nathan Shaner, Scintillon Institute.

From Biomedical Beat article July 2017: Chasing Fireflies—and Better Cellular Imaging Techniques

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

A mouse brain that was genetically modified so that subpopulations of its neurons glow. Researchers often study mice because they share many genes with people and can shed light on biological processes, development, and diseases in humans.

This image was captured using a light sheet microscope.

Related to image 6929 and video 6931.

Flower development is a carefully orchestrated, genetically programmed process that ensures that the male (stamen) and female (pistil) organs form in the right place and at the right time in the flower. In this image of young Arabidopsis flower buds, the gene SUPERMAN (red) is activated at the boundary between the cells destined to form the male and female parts. SUPERMAN activity prevents the central cells, which will ultimately become the female pistil, from activating the gene APETALA3 (green), which induces formation of male flower organs. The goal of this research is to find out how plants maintain cells (called stem cells) that have the potential to develop into any type of cell and how genetic and environmental factors cause stem cells to develop and specialize into different cell types. This work informs future studies in agriculture, medicine and other fields.

Genome editing using CRISPR/Cas9 is a rapidly expanding field of scientific research with emerging applications in disease treatment, medical therapeutics and bioenergy, just to name a few. This technology is now being used in laboratories all over the world to enhance our understanding of how living biological systems work, how to improve treatments for genetic diseases and how to develop energy solutions for a better future.

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.

This image of human red blood cells was obtained with the help of a scanning electron microscope, an instrument that uses a finely focused electron beam to yield detailed images of the surface of a sample.

This 1 1/2-minute video animation was produced for chemical biologist Stuart Schreiber's lab page. The animation shows how diverse chemical structures can be produced in the lab.

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

The photo shows a confocal microscopy image of perineuronal nets (PNNs), which are specialized extracellular matrix (ECM) structures in the brain. The PNN surrounds some nerve cells in brain regions including the cortex, hippocampus and thalamus. Researchers study the PNN to investigate their involvement stabilizing the extracellular environment and forming nets around nerve cells and synapses in the brain. Abnormalities in the PNNs have been linked to a variety of disorders, including epilepsy and schizophrenia, and they limit a process called neural plasticity in which new nerve connections are formed. To visualize the PNNs, researchers labeled them with Wisteria floribunda agglutinin (WFA)-fluorescein. Related to image 3741.

The structure of the endothelium, the thin layer of cells that line our arteries and veins, is visible here. The endothelium is like a gatekeeper, controlling the movement of materials into and out of the bloodstream. Endothelial cells are held tightly together by specialized proteins that function like strong ropes (red) and others that act like cement (blue).

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

Proteins in the neural tissues of this zebrafish embryo direct cells to line up and form the neural tube, which will become the spinal cord and brain. Studies of zebrafish embryonic development may help pinpoint the underlying cause of common neural tube defects--such as spina bifida--which occur in about 1 in 1,000 newborn children.

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.

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 absent in the filopodi-like structures based leading edge of ARPC3-/- fibroblasts cells. Related to images 3328, 3330, 3331, 3332, and 3333.

Phenylalanine tRNA showing the anticodon (yellow) and the amino acid, phenylalanine (blue and red spheres).