A white poppy. View cropped image of a poppy here 3423.

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

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.

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).

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.

Acetylsalicylate (bottom) is the aspirin of today. Adding a chemical tag called an acetyl group (shaded box, bottom) to a molecule derived from willow bark (salicylate, top) makes the molecule less acidic (and easier on the lining of the digestive tract), but still effective at relieving pain. See image 2529 for an unlabeled version of this illustration. Featured in Medicines By Design.

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. Here, researchers crystallized bound pairs of CCD-1 molecules and molecules of the antibiotic cefotaxime. This enabled their structure to be studied using X-ray crystallography.

Related to images 6765, 6766, and 6767.

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

A red poppy.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. Circadian rhythms are influenced by light and regulated by the brain’s suprachiasmatic nucleus (SCN), sometimes referred to as a master clock. Learn more in NIGMS’ circadian rhythms fact sheet. See 6614 for the Spanish version of this infographic.

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.

A cropped image of a white poppy. View poppy uncropped here 3424.

These yeast cells were exposed to a glucose (sugar) shortage. This caused the cells to compartmentalize HMGCR (green)—an enzyme involved in making cholesterol—to a patch on the nuclear envelope next to the vacuole/lysosome (purple). This process enhanced HMGCR activity and helped the yeast adapt to the glucose shortage. Researchers hope that understanding how yeast regulate cholesterol could ultimately lead to new ways to treat high cholesterol in people. This image was captured using a fluorescence microscope.

Drosophila adult brain showing that an adipokine (fat hormone) generates a response from neurons (aqua) and regulates insulin-producing neurons (red).

Related to images 6982, 6983, and 6984.

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.

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.

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.

The world's smallest motor, ATP synthase, generates energy for the cell. See image 2518 for a labeled version of this illustration. Featured in The Chemistry of Health.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3415, 3417, 3418, and 3419.

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.

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 color version of Image 3481.

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

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).

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3415, 3416, 3417, 3418, and 3419.

This animation shows atoms of the HIV capsid, the shell that encloses the virus's genetic material. Scientists determined the exact structure of the capsid using a variety of imaging techniques and analyses. They then entered this data into a supercomputer to produce this image. Related to image 3477.

Dynein (green) is a motor protein that “walks” along microtubules (red, part of the cytoskeleton) and carries its cargo along with it. This video was captured through fluorescence microscopy.

The TRPA1 protein is responsible for the burn you feel when you taste a bite of sushi topped with wasabi. Known therefore informally as the "wasabi receptor," this protein forms pores in the membranes of nerve cells that sense tastes or odors. Pungent chemicals like wasabi or mustard oil cause the pores to open, which then triggers a tingling or burn on our tongue. This receptor also produces feelings of pain in response to chemicals produced within our own bodies when our tissues are damaged or inflamed. Researchers used cryo-EM to reveal the structure of the wasabi receptor at a resolution of about 4 angstroms (a credit card is about 8 million angstroms thick). This detailed structure can help scientists understand both how we feel pain and how we can limit it by developing therapies to block the receptor. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail.

This image is a computer-generated model of the approximately 4.2 million atoms of the HIV capsid, the shell that contains the virus' genetic material. Scientists determined the exact structure of the capsid and the proteins that it's made of using a variety of imaging techniques and analyses. They then entered these data into a supercomputer that produced the atomic-level image of the capsid. This structural information could be used for developing drugs that target the capsid, possibly leading to more effective therapies. Related to image 6601.

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 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 atomic structure of the morphine biosynthetic enzyme salutaridine reductase bound to the cofactor NADPH. The substrate salutaridine is shown entering the active site.

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.

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

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.

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.

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

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.

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