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.

In this image of a stained fruit fly ovary, the ovary is packed with immature eggs (with DNA stained blue). The cytoskeleton (in pink) is a collection of fibers that gives a cell shape and support. The signal-transmitting molecules like STAT (in yellow) are common to reproductive processes in humans. Researchers used this image to show molecular staining and high-resolution imaging techniques to students.

Like a watch wrapped around a wrist, a special enzyme encircles the double helix to repair a broken strand of DNA. Without molecules that can mend such breaks, cells can malfunction, die, or become cancerous. Related to image 3493.

Cytoplasmic linker protein (CLIP)-170 is a microtubule plus-end-tracking protein that regulates microtubule dynamics and links microtubule ends to different intracellular structures. In this movie, the gene for CLIP-170 has been fused with green fluorescent protein (GFP). When the protein is expressed in cells, the activities can be monitored in real time. Here, you can see CLIP-170 streaming towards the edges of the cell.

In the top snapshots, the brain of a sleep-deprived fruit fly glows orange, marking high concentrations of a synaptic protein called Bruchpilot (BRP) involved in communication between neurons. The color particularly lights up brain areas associated with learning. By contrast, the bottom images from a well-rested fly show lower levels of the protein. These pictures illustrate the results of an April 2009 study showing that sleep reduces the protein's levels, suggesting that such "downscaling" resets the brain to normal levels of synaptic activity and makes it ready to learn after a restful night.

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

Bacillus anthracis (anthrax) cells being killed by a fluorescent trans-translation inhibitor, which disrupts bacterial protein synthesis. The inhibitor is naturally fluorescent and looks blue when it is excited by ultraviolet light in the microscope. This is a black-and-white version of Image 3525.

This image of the human brain uses colors and shapes to show neurological differences between two people. The blurred front portion of the brain, associated with complex thought, varies most between the individuals. The blue ovals mark areas of basic function that vary relatively little. Visualizations like this one are part of a project to map complex and dynamic information about the human brain, including genes, enzymes, disease states, and anatomy. The brain maps represent collaborations between neuroscientists and experts in math, statistics, computer science, bioinformatics, imaging, and nanotechnology.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. In this image, a cardiac muscle-restricted promoter drives firefly luciferase expression. This is the lateral and overhead (Bottom) view.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.
For more information about the illumated area go to 3559.

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. 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.

Model of the enzyme nicotinic acid phosphoribosyltransferase. This enzyme, from the archaebacterium, Pyrococcus furiosus, is expected to be structurally similar to a clinically important human protein called B-cell colony enhancing factor based on amino acid sequence similarities and structure prediction methods. The structure consists of identical protein subunits, each shown in a different color, arranged in a ring.

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.

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.

During DNA replication, each strand of the original molecule acts as a template for the synthesis of a new, complementary DNA strand. See image 2543 for an unlabeled version of this illustration. Featured in The New Genetics.

A colorized scanning electron micrograph of bacteria. Scanning electron microscopes allow scientists to see the three-dimensional surface of their samples.

Human embryonic stem cells were differentiated into cells like those found in the pancreas (blue), which give rise to insulin-producing cells (red). When implanted in mice, the stem cell-derived pancreatic cells can replace the insulin that isn't produced in type 1 diabetes. Image and caption information courtesy of the California Institute for Regenerative Medicine.

In plants, as in animals, stem cells can transform into a variety of different cell types. The stem cells at the growing tip of this Arabidopsis plant will soon become flowers. Arabidopsis is frequently studied by cellular and molecular biologists because it grows rapidly (its entire life cycle is only 6 weeks), produces lots of seeds, and has a genome that is easy to manipulate.

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

A mouse liver glows after being tagged with specially designed infrared-fluorescent protein (IFP). Since its discovery in 1962, green fluorescent protein (GFP) has become an invaluable resource in biomedical imaging. But because of its short wavelength, the light that makes GFP glow doesn't penetrate far in whole animals. So University of California, San Diego cell biologist Roger Tsien--who shared the 2008 Nobel Prize in chemistry for groundbreaking work with GFP--made infrared-fluorescent proteins (IFPs) that shine under longer-wavelength light, allowing whole-body imaging in small animals.

Multicellular yeast called snowflake yeast that researchers created through many generations of directed evolution from unicellular yeast. Cells are connected to one another by their cell walls, shown in blue. Stained cytoplasm (green) and membranes (magenta) show that the individual cells remain separate. This image was captured using spinning disk confocal microscopy.

Related to images 6969 and 6971.

Melanoma (skin cancer) cells undergoing programmed cell death, also called apoptosis. This process was triggered by raising the pH of the medium that the cells were growing in. Melanoma in people cannot be treated by raising pH because that would also kill healthy cells. This video was taken using a differential interference contrast (DIC) microscope.

Normal mice, like the B6 breed pictured on the left, develop scars when their ears are pierced. The Murphy Roths Large (MRL) mice pictured on the right can grow back lost ear tissue thanks to an inactive version of the p21 gene. When researchers knocked out that same gene in other mouse breeds, their ears also healed completely without scarring. Journal Article: Clark, L.D., Clark, R.K. and Heber-Katz, E. 1998. A new murine model for mammalian wound repair and regeneration. Clin Immunol Immunopathol 88: 35-45.

The small intestine is where most of our nutrients from the food we eat are absorbed into the bloodstream. The walls of the intestine contain small finger-like projections called villi which increase the organ's surface area, enhancing nutrient absorption. It consists of the duodenum, which connects to the stomach, the jejenum and the ileum, which connects with the large intestine. Related to image 3389.

Model of the mandelate racemase enzyme from Bacillus subtilis, a bacterium commonly found in soil.

Glucose (top) and sucrose (bottom) are sugars made of carbon, hydrogen, and oxygen atoms. Carbohydrates include simple sugars like these and are the main source of energy for the human body.

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.

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 lined up.

Related to images 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, and 1019.

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

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Researchers crystallized complexes where a CCD-1 molecule and a molecule of the antibiotic cefotaxime were bound together. Then, they shot X-rays at the complexes to determine their structure—a process known as X-ray crystallography. This image shows the X-ray diffraction pattern of a complex.

Related to images 6764, 6766, and 6767.

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

These images model the molecular structures of three enzymes with critical roles in the life cycle of the human immunodeficiency virus (HIV). At the top, reverse transcriptase (orange) creates a DNA copy (yellow) of the virus's RNA genome (blue). In the middle image, integrase (magenta) inserts this DNA copy in the DNA genome (green) of the infected cell. At the bottom, much later in the viral life cycle, protease (turquoise) chops up a chain of HIV structural protein (purple) to generate the building blocks for making new viruses. See these enzymes in action on PDB 101’s video A Molecular View of HIV Therapy.

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.

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.

Bacterial biofilms are tightly knit communities of bacterial cells growing on, for example, solid surfaces, such as in water pipes or on teeth. Here, cells of the bacterium Bacillus subtilis have formed a biofilm in a laboratory culture. Researchers have discovered that the bacterial cells in a biofilm communicate with each other through electrical signals via specialized potassium ion channels to share resources, such as nutrients, with each other. This insight may help scientists to improve sanitation systems to prevent biofilms, which often resist common treatments, from forming and to develop better medicines to combat bacterial infections. See the Biomedical Beat blog post Bacterial Biofilms: A Charged Environment for more information.

Fruit fly sperm cells glow bright green when they express the gene for green fluorescent protein (GFP).

The lubber grasshopper, found throughout the southern United States, is frequently used in biology classes to teach students about the respiratory system of insects. Unlike mammals, which have red blood cells that carry oxygen throughout the body, insects have breathing tubes that carry air through their exoskeleton directly to where it's needed. This image shows the breathing tubes embedded in the weblike sheath cells that cover developing egg chambers.

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

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.

Nerve cells have long, invisibly thin fibers that carry electrical impulses throughout the body. Some of these fibers extend about 3 feet from the spinal cord to the toes.

Serum albumin (SA) is the most abundant protein in the blood plasma of mammals. SA has a characteristic heart-shape structure and is a highly versatile protein. It helps maintain normal water levels in our tissues and carries almost half of all calcium ions in human blood. SA also transports some hormones, nutrients and metals throughout the bloodstream. Despite being very similar to our own SA, those from other animals can cause some mild allergies in people. Therefore, some scientists study SAs from humans and other mammals to learn more about what subtle structural or other differences cause immune responses in the body.

Related to entries 3725 and 3675.

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.

This tropical scene, reminiscent of a postcard from Key West, is actually a petri dish containing an artistic arrangement of genetically engineered bacteria. The image showcases eight of the fluorescent proteins created in the laboratory of the late Roger Y. Tsien, a cell biologist at the University of California, San Diego. Tsien, along with Osamu Shimomura of the Marine Biology Laboratory and Martin Chalfie of Columbia University, share the 2008 Nobel Prize in chemistry for their work on green fluorescent protein-a naturally glowing molecule from jellyfish that has become a powerful tool for studying molecules inside living cells.

This image shows how the CRISPR surveillance complex is disabled by two copies of anti-CRISPR protein AcrF1 (red) and one AcrF2 (light green). These anti-CRISPRs block access to the CRISPR RNA (green tube) preventing the surveillance complex from scanning and targeting invading viral DNA for destruction.

Stanford University scientist Vijay Pande decided to couple the power of computers with the help of the public. He initiated a project called Folding@Home, a so-called distributed computing project in which anyone who wants to can download a screensaver that performs protein-folding calculations when a computer is not in use. Folding@Home is modeled on a similar project called SETI@Home, which is used to search for extraterrestrial intelligence.

This structure from an amyloid-forming prion protein shows one way beta sheets can stack. Image originally appeared in a December 2012 PLOS Biology paper.

Jon Lorsch at his swearing in as NIGMS director in August 2013. Also shown are Francis Collins, NIH Director, and Judith Greenberg, former NIGMS Acting Director.

Ribosomes are complex machines made up of more than 50 proteins and three or four strands of genetic material called ribosomal RNA (rRNA). The busy cellular machines make proteins, which are critical to almost every structure and function in the cell. To do so, they read protein-building instructions, which come as strands of messenger RNA. Ribosomes are found in all forms of cellular life—people, plants, animals, even bacteria. This illustration of a bacterial ribosome was produced using detailed information about the position of every atom in the complex. Several antibiotic medicines work by disrupting bacterial ribosomes but leaving human ribosomes alone. Scientists are carefully comparing human and bacterial ribosomes to spot differences between the two. Structures that are present only in the bacterial version could serve as targets for new antibiotic medications.

When a molecule arrives at a cell's outer membrane, the membrane creates a pouch around the molecule that protrudes inward. Directed by a protein called dynamin, the pouch then gets pinched off to form a vesicle that carries the molecule to the right place inside the cell. To better understand how dynamin performs its vital pouch-pinching role, researchers determined its structure. Based on the structure, they proposed that a dynamin "collar" at the pouch's base twists ever tighter until the vesicle pops free. Because cells absorb many drugs through vesicles, the discovery could lead to new drug delivery methods.

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.

Fluorescent markers show the interconnected web of tubes and compartments in the endoplasmic reticulum. The protein atlastin helps build and maintain this critical part of cells. The image is from a July 2009 news release.

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

This computer algorithm plots all feasible small carbon-based molecules as though they were cities on a map and identifies huge, unexplored spaces that may help fuel research into new drug therapies. Featured in the May 16, 2013 issue of Biomedical Beat.