The green spots in this mouse brain are cells labeled with Calling Cards, a technology that records molecular events in brain cells as they mature. Understanding these processes during healthy development can guide further research into what goes wrong in cases of neuropsychiatric disorders. Also fluorescently labeled in this image are neurons (red) and nuclei (blue). Calling Cards and its application are described in the Cell paper “Self-Reporting Transposons Enable Simultaneous Readout of Gene Expression and Transcription Factor Binding in Single Cells” by Moudgil et al.; and the Proceedings of the National Academy of Sciences paper “A viral toolkit for recording transcription factor–DNA interactions in live mouse tissues” by Cammack et al. The technology was also featured in the NIH Director’s Blog post The Amazing Brain: Tracking Molecular Events with Calling Cards.

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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.

Kinases are enzymes that add phosphate groups (red-yellow structures) to proteins (green), assigning the proteins a code. In this reaction, an intermediate molecule called ATP (adenosine triphosphate) donates a phosphate group from itself, becoming ADP (adenosine diphosphate). See image 2535 for a labeled version of this illustration. Featured in Medicines By Design.

Sketch of an egg cell.

These induced pluripotent stem cells (iPS cells) were derived from a woman's skin. Green and red indicate proteins found in reprogrammed cells but not in skin cells (TRA1-62 and NANOG). These cells can then develop into different cell types. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to image 3279.

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 separating to form the cores of two new cells.

Related to images 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019, and 1021.

The microtubule severing protein, katanin, localizes to chromosomes and regulates anaphase A in mitosis. The movement of chromosomes on the mitotic spindle requires the depolymerization of microtubule ends. The figure shows the mitotic localization of the microtubule severing protein katanin (green) relative to spindle microtubules (red) and kinetochores/chromosomes (blue). Katanin targets to chromosomes during both metaphase (top) and anaphase (bottom) and is responsible for inducing the depolymerization of attached microtubule plus-ends. This image was a finalist in the 2008 Drosophila Image Award.

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 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.

The G switch allows our bodies to respond rapidly to hormones. G proteins act like relay batons to pass messages from circulating hormones into cells. A hormone (red) encounters a receptor (blue) in the membrane of a cell. Next, a G protein (green) becomes activated and makes contact with the receptor to which the hormone is attached. Finally, the G protein passes the hormone's message to the cell by switching on a cell enzyme (purple) that triggers a response. See image 2536 and 2537 for other versions of this image. Featured in Medicines By Design.

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.

How far and fast an infectious disease spreads across a community depends on many factors, including transportation. These U.S. maps, developed as part of an international study to simulate and analyze disease spread, chart daily commuting patterns. They show where commuters live (top) and where they travel for work (bottom). Green represents the fewest number of people whereas orange, brown, and white depict the most. Such information enables researchers and policymakers to visualize how an outbreak in one area can spread quickly across a geographic region.

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

Motor neuron progenitors (green) were derived from human embryonic stem cells. Image and caption information courtesy of the California Institute for Regenerative Medicine.

This pig cell is in the process of dividing. The chromosomes (purple) have already replicated and the duplicates are being pulled apart by fibers of the cell skeleton known as microtubules (green). Studies of cell division yield knowledge that is critical to advancing understanding of many human diseases, including cancer and birth defects.

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.

Various views of a zebrafish head with blood vessels shown in purple. Researchers often study zebrafish because they share many genes with humans, grow and reproduce quickly, and have see-through eggs and embryos, which make it easy to study early stages of development.

This video was captured using a light sheet microscope.

Related to image 6934.

A global "map of the protein structure universe." The Berkeley Structural Genomics Center has developed a method to visualize the vast universe of protein structures in which proteins of similar structure are located close together and those of different structures far away in the space. This map, constructed using about 500 of the most common protein folds, reveals a highly non-uniform distribution, and shows segregation between four elongated regions corresponding to four different protein classes (shown in four different colors). Such a representation reveals a high-level of organization of the protein structure universe.

Composite image of beta-galactosidase showing how cryo-EM’s resolution has improved dramatically in recent years. Older images to the left, more recent to the right. Related to image 5882. NIH Director Francis Collins featured this on his blog on January 14, 2016.

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

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.

A study published in March 2012 used cryo-electron microscopy to determine the structure of the DNA replication origin recognition complex (ORC), a semi-circular, protein complex (yellow) that recognizes and binds DNA to start the replication process. The ORC appears to wrap around and bend approximately 70 base pairs of double stranded DNA (red and blue). Also shown is the protein Cdc6 (green), which is also involved in the initiation of DNA replication. The video shows the structure from different angles. See related image 3597.

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.

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.

Model of an enzyme, PanC, that is involved in the last step of vitamin B5 biosynthesis in Mycobacterium tuberculosis. PanC is essential for the growth of M. tuberculosis, which causes most cases of tuberculosis, and is therefore a potential drug target.

Cilia (cilium in singular) are complex molecular machines found on many of our cells. One component of cilia is the doublet microtubule, a major part of cilia’s skeletons that give them support and shape. This animated video illustrates the structure of doublet microtubules, which contain 451 protein chains that were mapped using cryo-electron microscopy. Image can be found here 6548.

Glide across an icy canyon, where you see smiling snowmen and waddling penguins. Toss a snowball, hear it smash against an igloo, and then watch it explode in bright colors. Psychologists David Patterson and Hunter Hoffman of the University of Washington in Seattle developed this virtual "Snow World" to test whether immersing someone in a pretend reality could ease pain during burn treatment and other medical procedures. They found that people fully engaged in the virtual reality experience reported 60 percent less pain. The technology offers a promising way to manage pain.

This network map shows the overlap (green) between the long QT syndrome (yellow) and epilepsy (blue) protein-interaction neighborhoods located within the human interactome. Researchers have learned to integrate genetic, cellular and clinical information to find out why certain medicines can trigger fatal heart arrhythmias. Featured in Computing Life magazine.

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.

This fiery image doesn’t come from inside a bubbling volcano. Instead, it shows animal cells caught in the act of making bubbles, or blebbing. Some cells regularly pinch off parts of their membranes to produce bubbles filled with a mix of proteins and fats. The bubbles (red) are called plasma-derived membrane vesicles, or PMVs, and can travel to other parts of the body where they may aid in cell-cell communication. The University of Texas, Austin, researchers responsible for this photo are exploring ways to use PMVs to deliver medicines to precise locations in the body.

This image, entered in the Biophysical Society’s 2017 Art of Science Image contest, used two-channel spinning disk confocal fluorescence microscopy. It was also featured in the NIH Director’s Blog in May 2017.

Actin is an essential protein in a cell's skeleton (cytoskeleton). It forms a dense network of thin filaments in the cell. Here, researchers have used a technique called stochastic optical reconstruction microscopy (STORM) to visualize the actin network in a cell in three dimensions. The actin strands were labeled with a dye called Alexa Fluor 647-phalloidin.  This image appears in a study published by Nature Methods, which reports how researchers use STORM to visualize the cytoskeleton.

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.

This image of a mammalian epithelial cell, captured in metaphase, was the winning image in the high- and super-resolution microscopy category of the 2012 GE Healthcare Life Sciences Cell Imaging Competition. The image shows microtubules (red), kinetochores (green) and DNA (blue). The DNA is fixed in the process of being moved along the microtubules that form the structure of the spindle.

The image was taken using the DeltaVision OMX imaging system, affectionately known as the "OMG" microscope, and was displayed on the NBC screen in New York's Times Square during the weekend of April 20-21, 2013. It was also part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

A fruit fly ovary, shown here, contains as many as 20 eggs. Fruit flies are not merely tiny insects that buzz around overripe fruit--they are a venerable scientific tool. Research on the flies has shed light on many aspects of human biology, including biological rhythms, learning, memory and neurodegenerative diseases. Another reason fruit flies are so useful in a lab (and so successful in fruit bowls) is that they reproduce rapidly. About three generations can be studied in a single month. Related to image 3607.

A 360-degree view of the molecule himastatin, which was first isolated from the bacterium Streptomyces himastatinicus. Himastatin shows antibiotic activity. The researchers who created this video developed a new, more concise way to synthesize himastatin so it can be studied more easily.

More information about the research that produced this video can be found in the Science paper “Total synthesis of himastatin” by D’Angelo et al.

Related to images 6848 and 6850.

The worm Caenorhabditis elegans is a popular laboratory animal because its small size and fairly simple body make it easy to study. Scientists use this small worm to answer many research questions in developmental biology, neurobiology, and genetics. This image, which was taken with transmission electron microscopy (TEM), shows a cross-section through C. elegans, revealing various internal structures labeled in the image. You can find a high-resolution image without the annotations at image 5759.

The image is from a figure in an article published in the journal eLife.

Time lapse series shows short dynamin assemblies (not visible) constricting a lipid tube to make a "beads on a string" appearance, then cutting off one of the beads i.e., catalyzing membrane fission). The lipids are fluorescent (artificially colored). Ramachandran R, Pucadyil T.J., Liu Y.W., Acharya S., Leonard M., Lukiyanchuk V., Schmid S.L. 2009. Membrane insertion of the pleckstrin homology domain variable loop 1 is critical for dynamin-catalyzed vesicle scission. Mol Biol Cell. 2009 20:4630-9.

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.

These cells are induced stem cells made from human adult skin cells that were genetically reprogrammed to mimic embryonic stem cells. The induced stem cells were made potentially safer by removing the introduced genes and the viral vector used to ferry genes into the cells, a loop of DNA called a plasmid. The work was accomplished by geneticist Junying Yu in the laboratory of James Thomson, a University of Wisconsin-Madison School of Medicine and Public Health professor and the director of regenerative biology for the Morgridge Institute for Research.

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 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.

The plasma membrane is a cell's protective barrier. See image 2523 for an unlabeled version of this illustration. Featured in The Chemistry of Health.

Microtubules (magenta) in neurons of the hippocampus, a part of the brain involved in learning and memory. Microtubules are strong, hollow fibers that provide structural support to cells. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6889, 6891, and 6892.

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.

Floral pattern emerging as two bacterial species, motile Acinetobacter baylyi and non-motile Escherichia coli (green), are grown together for 72 hours on 0.5% agar surface from a small inoculum in the center of a Petri dish.

See 6557 for a photo of this process at 24 hours on 0.75% agar surface.
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 6550 for a video of this process.

Model of a protein, antigen 85B, that is the most abundant protein exported by Mycobacterium tuberculosis, which causes most cases of tuberculosis. Antigen 85B is involved in building the bacterial cell wall and is an attractive drug target. Based on its structure, scientists have suggested a new class of antituberculous drugs.

Blood clots stop bleeding, but they also can cause heart attacks and strokes. A team led by computational biophysicist Klaus Schulten of the University of Illinois at Urbana-Champaign has revealed how a blood protein can give clots their lifesaving and life-threatening abilities. The researchers combined experimental and computational methods to animate fibrinogen, a protein that forms the elastic fibers that enable clots to withstand the force of blood pressure. This simulation shows that the protein, through a series of events, stretches up to three times its length. Adjusting this elasticity could improve how we manage healthful and harmful clots. NIH's National Center for Research Resources also supported this work. Featured in the March 19, 2008, issue of Biomedical Beat.

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

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 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.