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 2534 for an unlabeled version of this illustration. Featured in Medicines By Design.

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.

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.

Fat tissue from the abdomen of a genetically mosaic adult fruit fly. Genetic mosaicism means that the fly has cells with different genotypes even though it formed from a single zygote. This specific mosaicism results in accumulation of a critical fly adipokine (blue-green) within the fat tissue cells that have reduced expression a key nutrient sensing gene (in left panel). The dotted line shows the cells lacking the gene that is present and functioning in the rest of the cells. Nuclei are labelled in magenta. This image was captured using a confocal microscope and shows a maximum intensity projection of many slices.

Related to images 6982, 6984, and 6985.

A drug's life in the body. Medicines taken by mouth pass through the liver before they are absorbed into the bloodstream. Other forms of drug administration bypass the liver, entering the blood directly. See 2528 for a labeled version of this illustration. Featured in Medicines By Design.

The signal is obtained by allowing proteins in human serum to interact with glycan (polysaccharide) arrays. The arrays are shown in replicate so the pattern is clear. Each spot contains a specific type of glycan. Proteins have bound to the spots highlighted in green.

Adult Drosophila abdominal fat tissue showing cell nuclei labelled in magenta. The upper panel is from well-fed flies, and the lower panel is from flies that have been deprived of food for 4 hours. Starvation results in the accumulation of a key adipokine—a fat hormone (blue-green dots).

Related to images 6982, 6983, and 6985.

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 (lateral view).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For more information about the illumated area go to 3559.

Enzymes speed up chemical reactions by reducing the amount of energy needed for the reactions. The substrate (lactose) binds to the active site of the enzyme (lactase) and is converted into products (sugars).

To simulate the consequences of disrupting bacterial cell-to-cell communication, called quorum sensing, in the crypts (small chambers within the colon), the researchers experimented with an inhibitor molecule (i.e., antagonist) to turn off quorum sensing in methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant strain of bacteria that often causes human infections. In this experiment, a medium promoting bacterial growth flows through experimental chambers mimicking the colon environment. The chambers on the right contained no antagonist. In the left chambers, after being added to the flowing medium, the quorum-sensing-inhibiting molecules quickly spread throughout the crevices, inactivating quorum sensing and reducing colonization. These results suggest a potential strategy for addressing MRSA virulence via inhibitors of bacterial communication. You can read more about this research here.

Ionic and covalent bonds hold molecules, like sodium chloride and chlorine gas, together. Hydrogen bonds among molecules, notably involving water, also play an important role in biology. See image 2520 for a labeled version of this illustration. Featured in The Chemistry of Health.

A drug's life in the body. Medicines taken by mouth (oral) pass through the liver before they are absorbed into the bloodstream. Other forms of drug administration bypass the liver, entering the blood directly. See 2527 for an unlabeled version of this illustration. Featured in Medicines By Design.

Los ritmos circadianos son cambios físicos, mentales y de comportamiento que siguen un ciclo de 24 horas. Los ritmos circadianos se ven influenciados por la luz y están regulados por el núcleo supraquiasmático del cerebro, a veces denominado el reloj principal.

Vea 6613 para la versión en inglés de esta infografía.

Zinc is required for the function of more than 300 enzymes, including those that help regulate gene expression, in various organisms including humans. Researchers study how plants acquire, sequester and distribute zinc to find ways to increase the zinc content of crops to improve human health. Using synchrotron X-ray fluorescence technology, they created this heat map of zinc levels in an Arabidopsis thaliana plant leaf. This image is a winner of the 2015 FASEB Bioart contest and was featured in the NIH Director's blog.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3416, 3417, 3418, and 3419.

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.

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.

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.

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 image, researchers have created a T-cell receptor pathway consisting of 12 proteins outside the cell on an artificial membrane. The image shows two key steps during the signaling process: 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 video 3786.

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

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

Fourteen neurons (magenta) in the adult Drosophila brain produce insulin, and fat tissue sends packets of lipids to the brain via the lipoprotein carriers (green). This image was captured using a confocal microscope and shows a maximum intensity projection of many slices.

Related to images 6983, 6984, and 6985.

Drugs enter different layers of skin via intramuscular, subcutaneous, or transdermal delivery methods. See image 2531 for an unlabeled version of this illustration. Featured in Medicines By Design.

A representation of a patient’s brain waves after receiving the anesthetic propofol. All anesthetics create brain wave changes that vary depending on the patient’s age and the type and dose of anesthetic used. These changes are visible in raw electroencephalogram (EEG) readings, but they’re easier to interpret using a spectrogram where the signals are broken down by time (x-axis), frequency (y-axis), and power (color scale). This spectrogram shows the changes in brain waves before, during, and after propofol-induced anesthesia. The patient is unconscious from minute 5, upon propofol administration, through minute 69 (change in power and frequency). But, between minutes 35 and 48, the patient fell into a profound state of unconsciousness (disappearance of dark red oscillations between 8 to 12 Hz), which required the anesthesiologist to adjust the rate of propofol administration. The propofol was stopped at minute 62 and the patient woke up around minute 69.

Colonies of bacteria growing despite high concentrations of antibiotics. These colonies are visible both by eye, as seen on the left, and by bioluminescence imaging, as seen on the right. The bioluminescent color indicates the metabolic activity of these bacteria, with their red centers indicating high metabolism.

More information about the research that produced this image can be found in the Antimicrobial Agents and Chemotherapy paper “Novel aminoglycoside-tolerant phoenix colony variants of Pseudomonas aeruginosa” by Sindeldecker et al.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Using X-ray crystallography, researchers determined the structure of a CCD-1 molecule and a molecule of the antibiotic cefotaxime bound together. The structure revealed that CCD-1 provides extensive hydrogen bonding and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6767.

Moving protein or other molecules to specific cells to treat or examine them has been a major biological challenge. Scientists have now developed a technique for delivering chemicals to individual cells. The approach involves gold nanowires that, for example, can carry tumor-killing proteins. The advance was possible after researchers developed electric tweezers that could manipulate gold nanowires to help deliver drugs to single cells.

This movie shows the manipulation of the nanowires for drug delivery to a single cell. To learn more about this technique, see this post in the Computing Life series.

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.

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.

Active site of E. coli response regulator PhoB.

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.

Drugs enter different layers of skin via intramuscular, subcutaneous, or transdermal delivery methods. See image 2532 for a labeled version of this illustration. Featured in Medicines By Design.

This image shows the structure of the CYP17A1 enzyme (ribbons colored from blue N-terminus to red C-terminus), with the associated heme colored black. The prostate cancer drug abiraterone is colored gray. Cytochrome P450 enzymes bind to and metabolize a variety of chemicals, including drugs. Cytochrome P450 17A1 also helps create steroid hormones. Emily Scott's lab is studying how CYP17A1 could be selectively inhibited to treat prostate cancer. She and graduate student Natasha DeVore elucidated the structure shown using X-ray crystallography. Dr. Scott created the image (both white bg and transparent bg) for the NIGMS image gallery. See the "Medium-Resolution Image" for a PNG version of the image that is transparent.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3414, 3415, 3416, 3417, 3418, and 3419.

This wreath represents the molecular structure of a protein, Cas4, which is part of a system, known as CRISPR, that bacteria use to protect themselves against viral invaders. The green ribbons show the protein's structure, and the red balls show the location of iron and sulfur molecules important for the protein's function. Scientists harnessed Cas9, a different protein in the bacterial CRISPR system, to create a gene-editing tool known as CRISPR-Cas9. Using this tool, researchers are able to study a range of cellular processes and human diseases more easily, cheaply and precisely. In December, 2015, Science magazine recognized the CRISPR-Cas9 gene-editing tool as the "breakthrough of the year." Read more about Cas4 in the December 2015 Biomedical Beat post A Holiday-Themed Image Collection.

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 difference in how the proteins in each compartment mix with water and with each other. These differences let them 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 3791, image 3792 and image 3793.

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.

Luciferase-based imaging enables visualization and quantification of internal organs and transplanted cells in live adult zebrafish. This image shows how luciferase-based imaging could be used to visualize the heart for regeneration studies (left), or label all tissues for stem cell transplantation (right).
For imagery of both the lateral and overhead view go to 3556.
For imagery of the overhead view go to 3557.
For imagery of the lateral view go to 3558.

Los ritmos circadianos son cambios físicos, mentales y conductuales que siguen un ciclo de 24 horas. Los ritmos circadianos típicos conducen a un nivel alto de energía durante la mitad del día (de 10 a.m. a 1 p.m.) y un bajón por la tarde. De noche, los ritmos circadianos hacen que la hormona melatonina aumente, lo que hace que la persona se sienta somnolienta.

Vea 6611 para la versión en inglés de esta infografía.

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

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.

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.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Using X-ray crystallography, researchers determined the structure of a complex between CCD-1 and the antibiotic cefotaxime (purple, yellow, and blue molecule). The structure revealed that CCD-1 provides extensive hydrogen bonding (shown as dotted lines) and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6766.

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.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. Typical circadian rhythms lead to high energy during the middle of the day (10 a.m. to 1 p.m.) and an afternoon slump. At night, circadian rhythms cause the hormone melatonin to rise, making a person sleepy.

Learn more in NIGMS’ circadian rhythms featured topics page.

See 6612 for the Spanish version of this infographic.

To become products, reactants must overcome an energy hill. See image 2526 for a labeled version of this illustration. Featured in The Chemistry of Health.

A protein called kinesin (blue) is in charge of moving cargo around inside cells and helping them divide. It's powered by biological fuel called ATP (bright yellow) as it scoots along tube-like cellular tracks called microtubules (gray).

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.

The molecule on the left is an electrostatic potential map of the van der Waals surface of the transition state for human purine nucleoside phosphorylase. The colors indicate the electron density at any position of the molecule. Red indicates electron-rich regions with negative charge and blue indicates electron-poor regions with positive charge. The molecule on the right is called DADMe-ImmH. It is a chemically stable analogue of the transition state on the left. It binds to the enzyme millions of times tighter than the substrate. This inhibitor is in human clinical trials for treating patients with gout. This image appears in Figure 4, Schramm, V.L. (2011) Annu. Rev. Biochem. 80:703-732.

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.