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.

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 video 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. This video was created for the NIH Director’s Blog post The Amazing Brain: Tracking Molecular Events with Calling Cards.

Related to image 6780.

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.

A model of the molecule himastatin overlaid on an image of Bacillus subtilis bacteria. Scientists first isolated himastatin from the bacterium Streptomyces himastatinicus, and the molecule shows antibiotic activity. The researchers who created this image developed a new, more concise way to synthesize himastatin so it can be studied more easily. They also tested the effects of himastatin and derivatives of the molecule on B. subtilis.

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

Related to image 6848 and video 6851.

Using a supercomputer to simulate the movement of atoms in a ribosome, researchers looked into the core of this protein-making nanomachine and took snapshots. The picture shows an amino acid (green) being delivered by transfer RNA (yellow) into a corridor (purple) in the ribosome. In the corridor, a series of chemical reactions will string together amino acids to make a protein. The research project, which tracked the movement of more than 2.6 million atoms, was the largest computer simulation of a biological structure to date. The results shed light on the manufacturing of proteins and could aid the search for new antibiotics, which typically work by disabling the ribosomes of bacteria.

T cells are white blood cells that are important in defending the body against bacteria, viruses and other pathogens. Each T cell carries proteins, called T-cell receptors, on its surface that are activated when they come in contact with an invader. This activation sets in motion a cascade of biochemical changes inside the T cell to mount a defense against the invasion. Scientists have been interested for some time what happens after a T-cell receptor is activated. One obstacle has been to study how this signaling cascade, or pathway, proceeds inside T cells.

In this video, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The video shows three key steps during the signaling process: phosphorylation of the T-cell receptor (green), clustering of a protein called linker for activation of T cells (LAT) (blue) and polymerization of the cytoskeleton protein actin (red). The findings show that the T-cell receptor signaling proteins self-organize into separate physical and biochemical compartments. This new system of studying molecular pathways outside the cells will enable scientists to better understand how the immune system combats microbes or other agents that cause infection.

To learn more how researchers assembled this T-cell receptor pathway, see this press release from HHMI's Marine Biological Laboratory Whitman Center. Related to image 3787.

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.

Yeast make bread, beer, and wine. And like us, yeast can reproduce sexually. A mother and father cell fuse and create one large cell that contains four offspring. When environmental conditions are favorable, the offspring are released, as shown here. Yeast are also a popular study subject for scientists. Research on yeast has yielded vast knowledge about basic cellular and molecular biology as well as about myriad human diseases, including colon cancer and various metabolic disorders.

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

Nucleotides in DNA are copied into RNA, where they are read three at a time to encode the amino acids in a protein. Many parts of a protein fold as the amino acids are strung together.

See image 2510 for a labeled version of this illustration.

Featured in The Structures of Life.

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.

The receptor is shown bound to an antagonist, eticlopride

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.

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.

Coronaviruses are enveloped viruses responsible for 30 percent of mild respiratory infections and atypical deadly pneumonia in humans worldwide. These deadly pneumonia include those caused by infections with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). The coronavirus spike glycoprotein mediates virus entry into cells and represents an important therapeutic target. The illustration shows a viral membrane decorated with spike glycoproteins; highlighted in red is a potential neutralization site, which is a protein sequence that might be used as a target for vaccines to combat viruses such as MERS-CoV and other coronaviruses.

Fruit flies are a common model organism for basic medical research.

Antibodies are among the most promising therapies for certain forms of cancer, but patients must take them intravenously, exposing healthy tissues to the drug and increasing the risk of side effects. A team of biochemists packed the anticancer antibodies into porous silica particles to deliver a heavy dose directly to tumors in mice.

Model based on X-ray crystallography of the structure of a small heat shock protein complex from the bacteria, Methanococcus jannaschii. Methanococcus jannaschii is an organism that lives at near boiling temperature, and this protein complex helps it cope with the stress of high temperature. Similar complexes are produced in human cells when they are "stressed" by events such as burns, heart attacks, or strokes. The complexes help cells recover from the stressful event.

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 graphic that resembles a firework was created from a picture of a fruit fly spermatid. This fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.

Featured in the March 15, 2012 issue of Biomedical Beat. Related to Hsp33 Figure 2, image 3355.

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 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.

The nucleus of a human fibroblast cell with chromatin—a substance made up of DNA and proteins—shown in various colors. Fibroblasts are one of the most common types of cells in mammalian connective tissue, and they play a key role in wound healing and tissue repair. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6887 and 6893.

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 and causes serious disease.

In this image, 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 video 5752.

This fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.

This network map shows molecular interactions (yellow) associated with a congenital condition that causes heart arrhythmias and the targets for drugs that alter these interactions (red and blue).

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.

This image shows a layer of retinal pigment epithelium cells derived from human embryonic stem cells, highlighting the nuclei (red) and cell surfaces (green). This kind of retinal cell is responsible for macular degeneration, the most common cause of blindness. Image and caption information courtesy of the California Institute for Regenerative Medicine. Related to image 3286

The receptor is shown bound to a small molecule peptide called CVX15.

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.

As an egg cell develops, a process called polarization controls what parts ultimately become the embryo's head and tail. This picture shows an egg of the fruit fly Drosophila. Red and green mark two types of signaling proteins involved in polarization. Disrupting these signals can scramble the body plan of the embryo, leading to severe developmental disorders.

The genetic code in DNA is transcribed into RNA, which is translated into proteins with specific sequences. During transcription, nucleotides in DNA are copied into RNA, where they are read three at a time to encode the amino acids in a protein. Many parts of a protein fold as the amino acids are strung together.

See image 2509 for an unlabeled version of this illustration.

Featured in The Structures of Life.

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

The membrane that surrounds a cell is made up of proteins and lipids. Depending on the membrane's location and role in the body, lipids can make up anywhere from 20 to 80 percent of the membrane, with the remainder being proteins. Cholesterol (green), which is not found in plant cells, is a type of lipid that helps stiffen the membrane.

The "epigenetic code" controls gene activity with chemical tags that mark DNA (purple diamonds) and the "tails" of histone proteins (purple triangles). These markings help determine whether genes will be transcribed by RNA polymerase. Genes hidden from access to RNA polymerase are not expressed. See image 2563 for a labeled version of this illustration. Featured in The New Genetics.

The activator cancer cell culture, right, contains a chemical that causes the cells to emit light when in the presence of immune cells.

During cell division, spindle pole bodies (glowing dots) move toward the ends of yeast cells to separate copied genetic information. Contractile rings (glowing bands) form in cells’ middles and constrict to help them split. This time-lapse video was captured using wide-field microscopy with deconvolution.

Related to images 6791, 6792, 6793, 6794, 6797, 6798, and video 6795.

A two-dimensional NMR spectrum of a protein, in this case a 2D 1H-15N HSQC NMR spectrum of a 228 amino acid DNA/RNA-binding protein.

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.

Hippocampal neuron from rodent brain with dendrites shown in blue. The hundreds of tiny magenta, green and white dots are the dendritic spines of excitatory synapses.

Map of microtubule growth rates. Rates are color coded. This is an example of NIH-supported research on single-cell analysis. Related to 2798 , 2799, 2801, 2802 and 2803.

The goal of the Protein Structure Initiative (PSI) is to determine the three-dimensional shapes of a wide range of proteins by solving the structures of representative members of each protein family found in nature. The collection of structures should serve as a valuable resource for biomedical research scientists.

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.

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.

Just as our bodies rely on bones for structural support, our cells rely on a cellular skeleton. In addition to helping cells keep their shape, this cytoskeleton transports material within cells and coordinates cell division. One component of the cytoskeleton is a protein called tubulin, shown here as thin strands.

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

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, 2453, and 2454.

RNA interference or RNAi is a gene-silencing process in which double-stranded RNAs trigger the destruction of specific RNAs. See 2558 for an unlabeled version of this illustration. Featured in The New Genetics.

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, 1049, 1050, 1051 and 1052.

The arrangement of identical molecular components can make a dramatic difference. For example, carbon atoms can be arranged into dull graphite (left) or sparkly diamonds (right). See image 2506 for an illustration without examples.