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.

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.

Peripheral nerve cells made from human embryonic stem cell-derived neural crest stem cells. The nuclei are shown in blue, and nerve cell proteins peripherin and beta-tubulin (Tuj1) are shown in green and red, respectively. Related to image 3264. Image is featured in October 2015 Biomedical Beat blog post Cool Images: A Halloween-Inspired Cell Collection.

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.

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

Influenza A infects a host cell when hemagglutinin grips onto glycans on its surface. Neuraminidase, an enzyme that chews sugars, helps newly made virus particles detach so they can infect other cells. Related to 213.

Multiphoton fluorescence image of HeLa cells with cytoskeletal microtubules (magenta) and DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. See related images 3518, 3519, 3521, 3522.

The proteasome is a critical multiprotein complex in the cell that breaks down and recycles proteins that have become damaged or are no longer needed. This movie shows how a protein substrate (red) is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region then gets engaged by the AAA+ motor of the proteasome (cyan), which initiates mechanical pulling, unfolding and movement of the protein into the proteasome's interior for cleavage into shorter protein pieces called peptides. During movement of the substrate, its ubiquitin modification gets cleaved off by the deubiquitinase Rpn11 (green), which sits directly above the entrance to the AAA+ motor pore and acts as a gatekeeper to ensure efficient ubiquitin removal, a prerequisite for fast protein breakdown by the 26S proteasome. Related to image 3763.

This slide shows the technologies that the Joint Center for Structural Genomics developed for going from gene to structure and how the technologies have been integrated into a high-throughput pipeline, including all of the steps from target selection, parallel expression, protein purification, automated crystallization trials, automated crystal screening, structure determination, validation, and publication.

A light microscope image shows the chromosomes, stained dark blue, in a dividing cell 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.

Embryonic stem cells store pre-activated Bax (red) in the Golgi, near the nucleus (blue). Featured in the June 21, 2012, issue of Biomedical Beat.

A cell in metaphase during mitosis: The copied chromosomes align in the middle of the spindle. Mitosis is responsible for growth and development, as well as for replacing injured or worn out cells throughout the body. For simplicity, mitosis is illustrated here with only six chromosomes.

The research organism Arabidopsis thaliana forms a large molecular machine called a resistosome to fight off infections. This illustration shows the top and side views of the fully-formed resistosome assembly (PDB entry 6J5T), composed of different proteins including one the plant uses as a decoy, PBL2 (dark blue), that gets uridylylated to begin the process of building the resistosome (uridylyl groups in magenta). Other proteins include RSK1 (turquoise) and ZAR1 (green) subunits. The ends of the ZAR1 subunits (yellow) form a funnel-like protrusion on one side of the assembly (seen in the side view). The funnel can carry out the critical protective function of the resistosome by inserting itself into the cell membrane to form a pore, which leads to a localized programmed cell death. The death of the infected cell helps protect the rest of the plant.

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.

Influenza A infects a host cell when hemagglutinin grips onto glycans on its surface. Neuraminidase, an enzyme that chews sugars, helps newly made virus particles detach so they can infect other cells. Related to 213. Featured in the March 2006, issue of Findings in "Viral Voyages."

Xenopus laevis, the African clawed frog, has long been used as a model organism for studying embryonic development. In this image, RNA encoding the transcription factor Sox 7 (dark blue) is shown to predominate at the vegetal pole, the yolk-rich portion, of a Xenopus laevis frog egg. Sox 7 protein is important to the regulation of embryonic development.

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.

Anaphase is the critical step during mitosis when sister chromosomes are disjoined and directed to opposite spindle poles, ensuring equal distribution of the genome during cell division. In this image, one pair of sister chromosomes at the top was lost and failed to divide after chemical inhibition of polo-like kinase 1. This image depicts chromosomes (blue) separating away from the spindle mid-zone (red). Kinetochores (green) highlight impaired movement of some chromosomes away from the mid-zone or the failure of sister chromatid separation (top). Scientists are interested in detailing the signaling events that are disrupted to produce this effect. The image is a volume projection of multiple deconvolved z-planes acquired with a Nikon widefield fluorescence microscope.

This image was chosen as a winner of the 2016 NIH-funded research image call. The research that led to this image was funded by NIGMS.

Related to image 5765.

Lysosomes (yellow) and detyrosinated microtubules (light blue). Lysosomes are bubblelike organelles that take in molecules and use enzymes to break them down. Microtubules are strong, hollow fibers that provide structural support to cells. The researchers who took this image found that in epithelial cells, detyrosinated microtubules are a small subset of fibers, and they concentrate lysosomes around themselves. This image was captured using Stochastic Optical Reconstruction Microscopy (STORM).

Related to images 6890, 6891, and 6892.

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.

Actin (purple), microtubules (yellow), and nuclei (green) are labeled in these cells by immunofluorescence. This image won first place in the Nikon 2003 Small World photo competition.

It has been said that gastrulation is the most important event in a person's life. This part of early embryonic development transforms a simple ball of cells and begins to define cell fate and the body axis. In a study published in Science magazine in March 2012, NIGMS grantee Bob Goldstein and his research group studied how contractions of actomyosin filaments in C. elegans and Drosophila embryos lead to dramatic rearrangements of cell and embryonic structure. This research is described in detail in the following article: "Triggering a Cell Shape Change by Exploiting Preexisting Actomyosin Contractions." In these images, myosin (green) and plasma membrane (red) are highlighted at four timepoints in gastrulation in the roundworm C. elegans. The blue highlights in the top three frames show how cells are internalized, and the site of closure around the involuting cells is marked with an arrow in the last frame. See related video 3334.

Learn how curiosity about the world and our cells is key to scientific discoveries. Discover more resources from NIGMS’ Pathways collaboration with Scholastic. View the video on YouTube for closed captioning.

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.

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.

Electron density maps such as this one are generated from the diffraction patterns of X-rays passing through protein crystals. These maps are then used to generate a model of the protein's structure by fitting the protein's amino acid sequence (yellow) into the observed electron density (blue).

This painting shows a cross section of a small respiratory droplet, like the ones that are thought to transmit SARS-CoV-2, the virus that causes COVID-19. The virus is shown in pink, and the droplet is also filled with molecules that are present in the respiratory tract, including mucins (green), pulmonary surfactant proteins and lipids (blue), and antibodies (tan).

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

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

This illustration shows vesicle traffic inside a cell. The double membrane that bounds the nucleus flows into the ribosome-studded rough endoplasmic reticulum (purple), where membrane-embedded proteins are manufactured. Proteins are processed and lipids are manufactured in the smooth endoplasmic reticulum (blue) and Golgi apparatus (green). Vesicles that fuse with the cell membrane release their contents outside the cell. The cell can also take in material from outside by having vesicles pinch off from the cell membrane.

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.

Although they are tiny, microbes that are growing in confined spaces can generate a lot of pressure. In this video, yeast cells grow in a small chamber called a microfluidic bioreactor. As the cells multiply, they begin to bump into and squeeze each other, resulting in periodic bursts of cells moving into different parts of the chamber. The continually growing cells also generate a lot of pressure--the researchers conducting these experiments found that the pressure generated by the cells can be almost five times higher than that in a car tire--about 150 psi, or 10 times the atmospheric pressure. Occasionally, this pressure even caused the small reactor to burst. By tracking the growth of the yeast or other cells and measuring the mechanical forces generated, scientists can simulate microbial growth in various places such as water pumps, sewage lines or catheters to learn how damage to these devices can be prevented. To learn more how researchers used small bioreactors to gauge the pressure generated by growing microbes, see this press release from UC Berkeley.

A three-dimensional representation of the structure of E2, a key antigen protein involved with hepatitis C virus infection.

The illustration shows the capsid of human immunodeficiency virus (HIV) whose molecular features were resolved with cryo-electron microscopy (cryo-EM). On the left, the HIV capsid is "naked," a state in which it would be easily detected by and removed from cells. However, as shown on the right, when the viral capsid binds to and is covered with a host protein, called cyclophilin A (shown in red), it evades detection and enters and invades the human cell to use it to establish an infection. To learn more about how cyclophilin A helps HIV infect cells and how scientists used cryo-EM to find out the mechanism by which the HIV capsid attaches to cyclophilin A, see this news release by the University of Illinois. A study reporting these findings was published in the journal Nature Communications.

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

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.

Model of the enzyme aminopeptidase N from the human pathogen Neisseria meningitidis, which can cause meningitis epidemics. The structure provides insight on the active site of this important molecule.

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.

In vivo vascular development in kdr:GFP frogs. Related to images 3403 and 3405.

The human genome contains much of the information needed for every cell in the body to function. However, different types of cells often need different types of information. Access to DNA is controlled, in part, by how tightly it’s wrapped around proteins called histones to form nucleosomes. The complex shown here, from yeast cells (PDB entry 6Z6P), includes several histone deacetylase (HDAC) enzymes (green and blue) bound to a nucleosome (histone proteins in red; DNA in yellow). The yeast HDAC enzymes are similar to the human enzymes. Two enzymes form a V-shaped clamp (green) that holds the other others, a dimer of the Hda1 enzymes (blue). In this assembly, Hda1 is activated and positioned to remove acetyl groups from histone tails.

This illustration shows, in simplified terms, how the CRISPR-Cas9 system can be used as a gene-editing tool.

Frame 1 shows the two components of the CRISPR system: a strong cutting device (an enzyme called Cas9 that can cut through a double strand of DNA), and a finely tuned targeting device (a small strand of RNA programmed to look for a specific DNA sequence).

In frame 2, the CRISPR machine locates the target DNA sequence once inserted into a cell.

In frame 3, the Cas9 enzyme cuts both strands of the DNA.

Frame 4 shows a repaired DNA strand with new genetic material that researchers can introduce, which the cell automatically incorporates into the gap when it repairs the broken DNA.

For an explanation and overview of the CRISPR-Cas9 system, see the iBiology video.

Download the individual frames: Frame 1, Frame 2, Frame 3, and Frame 4.

Sepsis is the body’s overactive and extreme response to an infection. More than 1.7 million people get sepsis each year in the United States. Without prompt treatment, sepsis can lead to tissue damage, organ failure, and death. Many NIGMS-supported researchers are working to improve sepsis diagnosis and treatment. Learn more with our sepsis featured topic page.

See 6551 for the Spanish version of this infographic.

These microscopic roundworms, called Caenorhabditis elegans, lack eyes and the opsin proteins used by visual systems to detect colors. However, researchers found that the worms can still sense the color of light in a way that enables them to avoid pigmented toxins made by bacteria. This image was captured using a stereo microscope.

Meiosis is used to make sperm and egg cells. During meiosis, a cell's chromosomes are copied once, but the cell divides twice. During mitosis, the chromosomes are copied once, and the cell divides once. For simplicity, cells are illustrated with only three pairs of chromosomes.

See image 1333 for an unlabeled version of this illustration.

Recombinant proteins such as the prion protein shown here are often used to model how proteins misfold and sometimes polymerize in neurodegenerative disorders. This prion protein was expressed in E. coli, purified and fibrillized at pH 7. Image taken in 2004 for a research project by Roger Moore, Ph.D., at Rocky Mountain Laboratories that was published in 2007 in Biochemistry. This image was not used in the publication.

HIV is a retrovirus, a type of virus that carries its genetic material not as DNA but as RNA. Long before anyone had heard of HIV, researchers in labs all over the world studied retroviruses, tracing out their life cycle and identifying the key proteins the viruses use to infect cells. When HIV was identified as a retrovirus, these studies gave AIDS researchers an immediate jump-start. The previously identified viral proteins became initial drug targets. See images 2513 and 2514 for other versions of this illustration. Featured in The Structures of Life.

The extracellular matrix (ECM) is most prevalent in connective tissues but also is present between the stems (axons) of nerve cells. The axons of nerve cells are surrounded by the ECM encasing myelin-supplying Schwann cells, which insulate the axons to help speed the transmission of electric nerve impulses along the axons.

Hydra magnipapillata is an invertebrate animal used as a model organism to study developmental questions, for example the formation of the body axis.

Gram-negative bacteria perform molecular acrobatics just to eat. Because they're encased by two membranes, they must haul nutrients across both. To test one theory of how the bacteria manage this feat, researchers used computer simulations of two proteins involved in importing vitamin B12. Here, the protein (red) anchored in the inner membrane of bacteria tugs on a much larger protein (green and blue) in the outer membrane. Part of the larger protein unwinds, creating a pore through which the vitamin can pass.

Cells use bubble-like structures called vesicles (yellow) to import, transport, and export cargo and in cellular communication. A single cell may be filled with thousands of moving vesicles.

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