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.

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 process involves significant shape changes on the part of the nurse cells (blue), which are powered by wavelike activity of the protein myosin (red). This image was captured using a confocal laser scanning microscope. Related to video 6754.

A computer model of the cell membrane, where the plasma membrane is red, endoplasmic reticulum is yellow, and mitochondria are blue. This image relates to a July 27, 2009 article in Computing Life.

Multiple actin filaments (magenta) are organized around a dynamin helical polymer (rainbow colored) in this model derived from cryo-electron tomography. By bundling actin, dynamin increases the strength of a cell’s skeleton and plays a role in cell-cell fusion, a process involved in conception, development, and regeneration.

Cell division is an incredibly coordinated process. It not only ensures that the new cells formed during this event have a full set of chromosomes, but also that they are endowed with all the cellular materials, including proteins, lipids and small functional compartments called organelles, that are required for normal cell activity. This proper apportioning of essential cell ingredients helps each cell get off to a running start.

This image shows an electron microscopy (EM) thin section taken at 10,000x magnification of a dividing yeast cell over-expressing the protein ubiquitin, which is involved in protein degradation and recycling. The picture features mother and daughter endosome accumulations (small organelles with internal vesicles), a darkly stained vacuole and a dividing nucleus in close contact with a cadre of lipid droplets (unstained spherical bodies).  Other dynamic events are also visible,  such as spindle microtubules in the nucleus and endocytic pits at the plasma membrane.

These extensive details were revealed thanks to a preservation method involving high-pressure freezing, freeze-substitution and Lowicryl HM20 embedding.

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.

A macrophage—a type of immune cell that engulfs invaders—“eats” and is activated by a “two-faced” Janus particle. The particle is called “two-faced” because each of its two hemispheres is coated with a different type of molecule, shown here in red and cyan. During macrophage activation, a transcription factor tagged with a green fluorescence protein (NF-κB) gradually moves from the cell’s cytoplasm into its nucleus and causes DNA transcription. The distribution of molecules on “two-faced” Janus particles can be altered to control the activation of immune cells. Details on this “geometric manipulation” strategy can be found in the Proceedings of the National Academy of Sciences paper "Geometrical reorganization of Dectin-1 and TLR2 on single phagosomes alters their synergistic immune signaling" by Li et al. and the Scientific Reports paper "Spatial organization of FcγR and TLR2/1 on phagosome membranes differentially regulates their synergistic and inhibitory receptor crosstalk" by Li et al. This video was captured using epi-fluorescence microscopy.

Related to video 6800.

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.

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

Learn about basic science, sometimes called “pure” or “fundamental” science, and how it contributes to the development of medical treatments. Discover more resources from NIGMS’ Pathways collaboration with Scholastic. View the video on YouTube for closed captioning.

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

In the absence of the engulfment receptor Draper, salivary gland cells (light blue) persist in the thorax of a developing Drosophila melanogaster pupa. See image 2758 for a cross section of a normal pupa that does express Draper.

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.

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.

La sepsis o septicemia es la respuesta fulminante y extrema del cuerpo a una infección. En los Estados Unidos, más de 1.7 millones de personas contraen sepsis cada año. Sin un tratamiento rápido, la sepsis puede provocar daño de los tejidos, insuficiencia orgánica y muerte. El NIGMS apoya a muchos investigadores en su trabajo para mejorar el diagnóstico y el tratamiento de la sepsis.

Vea 6536 para la versión en inglés de esta infografía.

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

A 3D model of the human endoplasmic reticulum membrane protein complex (EMC) that identifies its nine essential subunits. The EMC plays an important role in making membrane proteins, which are essential for all cellular processes. This is the first atomic-level depiction of the EMC. Its structure was obtained using single-particle cryo-electron microscopy.

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.

An image of the area of the mouse brain that serves as the 'master clock,' which houses the brain's time-keeping neurons. The nuclei of the clock cells are shown in blue. A small molecule called VIP, shown in green, enables neurons in the central clock in the mammalian brain to synchronize.

This image captures the spiral-shaped ovary of an anglerfish in cross-section. Once matured, these eggs will be released in a gelatinous, floating mass. For some species of anglerfish, this egg mass can be up to 3 feet long and include nearly 200,000 eggs.

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

Mitochondria are the powerhouses of the cells, generating the energy the cells need to do their tasks and to stay alive. Researchers have studied mitochondria for some time because when these cell organelles don't work as well as they should, several diseases develop. In this photograph of cow cells taken with a microscope, the mitochondria were stained in bright yellow to visualize them in the cell. The large blue dots are the cell nuclei and the gray web is the cytoskeleton of the cells.

Microtubules in African green monkey cells. Microtubules are strong, hollow fibers that provide cells with structural support. Here, the microtubules have been color-coded based on their distance from the microscope lens: purple is closest to the lens, and yellow is farthest away. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6889, 6890, and 6892.

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.

When we walk, muscles and nerves interact in intricate ways. This simulation, which is based on data from a six-foot-tall man, shows these interactions.

The proteasome is a critical multiprotein complex in the cell that breaks down and recycles proteins that have become damaged or are no longer needed. This movie shows how a protein substrate (red) is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region then gets engaged by the AAA+ motor of the proteasome (cyan), which initiates mechanical pulling, unfolding and movement of the protein into the proteasome's interior for cleavage into shorter protein pieces called peptides. During movement of the substrate, its ubiquitin modification gets cleaved off by the deubiquitinase Rpn11 (green), which sits directly above the entrance to the AAA+ motor pore and acts as a gatekeeper to ensure efficient ubiquitin removal, a prerequisite for fast protein breakdown by the 26S proteasome. Related to image 3763.

Planarians are freshwater flatworms that have powerful abilities to regenerate their bodies, which would seem to make them natural model organisms in which to study stem cells. But until recently, scientists had not been able to efficiently find the genes that regulate the planarian stem cell system. In this image, a single stem cell has given rise to a colony of stem cells in a planarian. Proliferating cells are red, and differentiating cells are blue. Quantitatively measuring the size and ratios of these two cell types provides a powerful framework for studying the roles of stem cell regulatory genes in planarians.

The enzyme CCP is found in the mitochondria of baker’s yeast. Scientists study the chemical reactions that CCP triggers, which involve a water molecule, iron, and oxygen. This structure was determined using an X-ray free electron laser.

This image shows the long, branched structures (axons) of nerve cells. Running horizontally across the middle of the photo is an axon wrapped in rings made of actin protein (green), which plays important roles in nerve cells. The image was captured with a powerful microscopy technique that allows scientists to see single molecules in living cells in real time. The technique is called stochastic optical reconstruction microscopy (STORM). It is based on technology so revolutionary that its developers earned the 2014 Nobel Prize in Chemistry. More information about this image can be found in: K. Xu, G. Zhong, X. Zhuang. Actin, spectrin and associated proteins form a periodic cytoskeleton structure in axons. Science 339, 452-456 (2013).

C. elegans, a tiny roundworm, 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 group of roundworms here 6582.
View closeup of roundworms here 6583.

Salk researchers captured the structure of a protein complex called an intasome (center) that lets viruses similar to HIV establish permanent infection in their hosts. The intasome hijacks host genomic material, DNA (white) and histones (beige), and irreversibly inserts viral DNA (blue). The image was created by Jamie Simon and Dmitry Lyumkis. Work that led to the 3D map was published in: Ballandras-Colas A, Brown M, Cook NJ, Dewdney TG, Demeler B, Cherepanov P, Lyumkis D, & Engelman AN. (2016). Cryo-EM reveals a novel octameric integrase structure for ?-retroviral intasome function. Nature, 530(7590), 358—361

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 6930 and video 6931.

The glial cells (black dots) and nerve cells (brown bands) in this developing fruit fly nerve cord formed normally despite the absence of the SPITZ protein, which blocks their impending suicide. The HID protein, which triggers suicide, is also lacking in this embryo.

Like a world of its own, this sphere represents all the known chemical reactions in the E. coli bacterium. The colorful circles on the surface symbolize sets of densely interconnected reactions. The lines between the circles show additional connecting reactions. The shapes inside the circles are landmark molecules, like capital cities on a map, that either act as hubs for many groups of reactions, are highly conserved among species, or both. Molecules that connect far-flung reactions on the sphere are much more conserved during evolution than molecules that connect reactions within a single circle. This statistical cartography could reveal insights about other complex systems, such as protein interactions and gene regulation networks.

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.

Cell-like compartments spontaneously emerge from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible. Regions without nuclei formed smaller compartments. 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: 6587, 6589, and 6590.

This image integrates the thousands of known molecular and genetic interactions happening inside our bodies using a computer program called Cytoscape. Images like this are known as network wiring diagrams, but Cytoscape creator Trey Ideker somewhat jokingly calls them "hairballs" because they can be so complicated, intricate and hard to tease apart. Cytoscape comes with tools to help scientists study specific interactions, such as differences between species or between sick and diseased cells. Related to 2737.

Many disease-causing microbes manipulate their host’s metabolism and cells for their own ends. Microsporidia—which are parasites closely related to fungi—infect and multiply inside animal cells, and take the rearranging of cells’ interiors to a new level. They reprogram animal cells such that the cells start to fuse, causing them to form long, continuous tubes. As shown in this image of the roundworm Caenorhabditis elegans, microsporidia (shown in magenta) have invaded the worm’s gut cells (shown in yellow; the cells’ nuclei are shown in blue) and have instructed the cells to merge. The cell fusion enables the microsporidia to thrive and propagate in the expanded space. Scientists study microsporidia in worms to gain more insight into how these parasites manipulate their host cells. This knowledge might help researchers devise strategies to prevent or treat infections with microsporidia. For more on the research into microsporidia, see this news release from the University of California San Diego. Related to images 5778 and 5779.

Cells walk along body surfaces via tiny "feet," called focal adhesions, that connect with the extracellular matrix. See image 2503 for a labeled version of this illustration.

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.

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 1052.

Cell-like compartments spontaneously emerge from scrambled frog eggs. Endoplasmic reticulum (red) and microtubules (green) are 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: 6587, 6588, and 6590.

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

In 2007, the FDA modified warfarin's label to indicate that genetic makeup may affect patient response to the drug. The widely used blood thinner is sold under the brand name Coumadin®. Scientists involved in the NIH Pharmacogenetics Research Network are investigating whether genetic information can be used to improve optimal dosage prediction for patients.

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

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.

Blood vessels at the back of the eye (retina) are used to diagnose glaucoma and diabetic eye disease. They also display characteristic changes in people with high blood pressure. In the image, the vessels appear green. It's not actually the vessels that are stained green, but rather filaments of a protein called actin that wraps around the vessels. Most of the red blood cells were replaced by fluid as the tissue was prepared for the microscope. The tiny red dots are red blood cells that remain in the vessels. The image was captured using confocal and 2-photon excitation microscopy for a project related to neurofibromatosis.

A 3-D model of the alkaloid serratezomine A shows the molecule's complex ring structure.

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.

The nucleolus is 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 video of nucleoli in the eggs of a commonly used lab animal, the frog Xenopus laevis, shows how each of the compartments (the granular component is shown in red, the fibrillarin in yellow-green, and the fibrillar center in blue) 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, image 3792 and image 3793.

Model of an enzyme, PanB, from Mycobacterium tuberculosis, the bacterium that causes most cases of tuberculosis. This enzyme is an attractive drug target.