The red spray pictured here may look like fireworks erupting across the night sky on July 4th, but it’s actually a rare glimpse of tiny protein strands called microtubules sprouting and growing from one another in a lab. Microtubules are the largest of the molecules that form a cell’s skeleton. When a cell divides, microtubules help ensure that each daughter cell has a complete set of genetic information from the parent. They also help organize the cell’s interior and even act as miniature highways for certain proteins to travel along.
As their name suggests, microtubules are hollow tubes made of building blocks called tubulins. Scientists know that a protein called XMAP215 adds tubulin proteins to the ends of microtubules to make them grow, but until recently, the way that a new microtubule starts forming remained a mystery.
Sabine Petry and her colleagues at Princeton University developed a new imaging method for watching microtubules as they develop and found an important clue to the mystery. They adapted a technique called total internal reflection fluorescence (TIRF) microscopy, which lit up only a tiny sliver of a sample from frog egg (Xenopus) tissue. This allowed the scientists to focus clearly on a few of the thousands of microtubules in a normal cell. They could then see what happened when they added certain proteins to the sample.
Cells are the basis of the living world. Our cells make up the tissues and organs of our bodies. Bacteria are also cells, living sometimes alone and sometimes in groups called biofilms. We think of cells mostly as staying in one spot, quietly doing their work. But in many situations, cells move, often very quickly. For example, when you get a cut, infection-fighting cells rally to the site, ready to gobble up bacterial intruders. Then, platelet cells along with proteins from blood gather and form a clot to stop any bleeding. And finally, skin cells surrounding the wound lay down scaffolding before gliding across the cut to close the wound.
This remarkable organization and timing is evident right from the start. Cells migrate within the embryo as it develops so that body tissues and organs end up in the right places. Harmful cells use movement as well, as when cells move and spread (metastasize) from an original cancer tumor to other parts of the body. Learning how and why cells move could give scientists new ways to guide those cells or turn off or slow down the movement when needed.
Scientists studying how humans and animals form, from a single cell at conception to a complex body at birth, are particularly interested in how and when cells move. They use research organisms like the fruit fly, Drosophila, to watch movements by small populations of cells. Still, watching cells migrate inside a living fly is challenging because the tissue is too dense to see individual cell movement. But moving those cells to a dish in the lab might cause them to behave differently than they do inside the fly. To solve this problem, NIGMS-funded researcher David Bilder and colleagues at the University of California, Berkeley, came up with a way to alter fly cells so they could track how the cells behave without removing them from the fly. They engineered the cells to lay down a glowing track of proteins behind them as they moved, leaving a traceable path through the fly’s tissue. The technique, called M-TRAIL (matrix-labeling technique for real-time and inferred location), allows the researchers to see where a cell travels and how long it takes to get there.
Bilder and his team first used M-TRAIL in flies to confirm the results of past studies of Drosophila ovaries in the lab using other imaging techniques. In addition, they found that M-TRAIL could be used to study a variety of cell types. The new technique also could allow a cell’s movement to be tracked over a longer period than other imaging techniques, which become toxic to cells in just a few hours. This is important, because cells often migrate for days to reach their final destinations.
The yellow-green glow from this summer’s fireflies teased my kids across the yard. Max and Stella zigzagged the grass, occasionally jumping into the air to cup a firefly in their hands and then proudly shouting, “I got one!”
Chasing fireflies on a summer night is a childhood rite of passage for many, including Nathan Shaner who grew up in New Jersey. “It was one of my favorite things about summer,” he recalls. “I’d catch them with my hands—I’d never jar them.”
Today, Shaner studies the science of bioluminescence, which gives fireflies and many other organisms the natural ability to emit light. His goal is to make bright bioluminescent tags that he and other scientists can use to study living cells in greater detail. “There’s this very beautiful thing that evolved in nature, and we can use it to enable new discoveries,” he says.
Thousands of organisms glow as a way to communicate, spook predators, lure prey or attract mates. There are a few terrestrial examples, such as fireflies, glowworm insect larvae and foxfire fungi, and many more aquatic ones, including types of marine plankton, fish, jellyfish, shrimp, squid and sea urchins. One research team estimated nearly three quarters of sea life have bioluminescent capabilities.
Every studied case of bioluminescence involves oxygen, a light-emitting pigment called luciferin and a protein called luciferase. Luciferase encourages the pigment’s reaction with oxygen, releasing energy in the form of light. Although many bioluminescent creatures have their own form of luciferase, they share just a handful of luciferins. For example, the luciferin called coelenterazine is found in many aquatic organisms.Continue reading “Chasing Fireflies—and Better Cellular Imaging Techniques”
Our eyes are the gateway to countless brilliant sights. However, as evidenced by the images on this page, the eye itself can be breathtakingly exquisite as well. This May, as we celebrate Healthy Vision Month with the National Eye Institute, we hope sharing the beauty hidden in your eyes will inspire you to take the necessary steps to protect your vision, prevent vision loss and make the most of the vision you have remaining.
Visit NEI to learn more about caring for your eyes.
Happy Healthy Vision Month!
This heart-shaped image shows two mouse skin cancer cells connected to each other with actin, a protein that is part of the cellular skeleton. Researchers use mouse cells like these to tease out the molecular methods that cancer uses to invade new tissues in the body. It turns out that actin plays an essential role.
Cells can move as a collective, or independently. Movement of an individual cell requires a series of carefully controlled steps. Among them, a cell must break contacts with its neighbor cells and change its connections to the proteins and fibers around it. In addition, it must sense and follow a chemical path through the tissue it lies in. To do this, a cell changes shape, molding its membrane into flaps or feet called protrusions reaching in the direction it is traveling. Actin, among a variety of other molecules, is involved in all of these steps, but especially the shape change, when it gathers inside the cell membrane to help form the protrusions. Continue reading “Actin’s Many Roles”
An exhibit called “Minerals in Medicine” opened at the NIH Clinical Center last month (see slideshow). The display features a fascinating overview of how dozens of minerals are used to create drugs and medical instruments useful in treating disease and maintaining health. The minerals ranged from commonplace ones like quartz, which is used to make medical instruments, to more exotic ones like hubnerite, a source of the metal tungsten, which is used in radiation shielding.
Inspired by this collection, which is co-sponsored by NIH and the Smithsonian Institution, we highlight here examples of “Metals in Medicine.”
Copper and Fat Metabolism
What does a metal like copper have to do with our ability to breakdown fat? Researchers explored this question by observing mice with Wilson’s disease—a rare, inherited condition that causes copper to accumulate in the liver, brain and other vital organs. The mice with the condition usually have larger deposits of fat compared to healthy mice. To confirm that fat metabolism is somehow compromised in these mice, the researchers treated them with a drug that induces the breakdown of fat. And indeed they found that less fat was metabolized in mice with the disease.
In an effort to investigate what role copper may be playing in fat metabolism, the researchers examined adipose tissue, or fat, cells under a microscope to track the metal’s interactions with various proteins in the cell. They discovered that copper inhibits an enzyme called PDE3. This enzyme usually prevents another enzyme called cAMP from helping to break down fat. The researchers concluded that copper actually promotes fat metabolism. This work shows that transition metal nutrients can play signaling roles, which has been previously thought to be restricted to alkali and alkaline earth metals like sodium, potassium and calcium.Continue reading “Metals in Medicine”
Science is beautiful.
For several years, we’ve used this blog to highlight pictures we think are cool, scientifically relevant and visually striking. The images were created by NIGMS-funded researchers in the process of doing their research. Many come from our Life: Magnified collection, which features dozens of stunning photos of life, close-up. We’ll continue to bring you interesting images and information here on Biomedical Beat, but if you can’t get enough of them, we have a new way to share our visual content with you: Instagram.
We’re pleased to announce the launch of our NIGMS Instagram account. We’ll highlight gorgeous images, and bring you the science behind them—straight from our mobile device to yours. Instagram lets us label our images with subject-specific hashtags. You can find our pictures by going on Instagram and searching for #NIGMS. If you’re already an Instagram user, you can follow us @NIGMS_NIH. You can even see our page using a web browser at https://www.instagram.com/nigms_nih/ . Let us know what you think!
Also, if you have any stunning images or videos that relate to scientific areas supported by NIGMS, please send them to us. They might end up on our Instagram feed!
What looks like the gossamer wings of a butterfly is actually the retina of a mouse, delicately snipped to lay flat and sparkling with fluorescent molecules. Researchers captured this image while investigating the promise of gene therapy for glaucoma, a progressive eye disease. It all happened at the National Center for Microscopy and Imaging Research (NCMIR) at the University of California, San Diego.
Glaucoma is the leading cause of irreversible blindness. It is characterized by the slow, steady death of certain nerve cells in the retina. If scientists can prevent the death of these cells, which are called retinal ganglion cells, it might be possible to slow the progression of glaucoma. Some researchers are examining the possibility of using gene therapy to do just that.
A major challenge of gene therapy is finding a way to get therapeutic genes into the right cells without damaging the cells in any way. Scientists have had success using a non-disease-causing virus (adeno-associated serotype 2) for this task. Continue reading “Lighting Up the Promise of Gene Therapy for Glaucoma”
Scientists have identified a new family of proteins that, like the targets of penicillin, help bacteria build their cell walls. The finding might reveal a new strategy for treating a range of bacterial diseases.
The protein family is nicknamed SEDS, because its members help control the shape, elongation, division and spore formation of bacterial cells. Now researchers have proof that SEDS proteins also play a role in constructing cell walls. This image shows the movement of a molecular machine that contains a SEDS protein as it constructs hoops of bacterial cell wall material.
Any molecule involved in building or maintaining cell walls is of immediate interest as a possible target for antibiotic drugs. That’s because animals, including humans, don’t have cell walls—we have cell membranes instead. So disabling cell walls, which bacteria need to survive, is a good way to kill bacteria without harming patients.
This strategy has worked for the first antibiotic drug, penicillin (and its many derivatives), for some 75 years. Now, many strains of bacteria have evolved to resist penicillins—and other antibiotics—making the drugs less effective.
According to the Centers for Disease Control and Prevention, drug-resistant strains of bacteria infect at least 2 million people, killing more than 20,000 of them in the U.S. every year. Identifying potential new drug targets, like SEDS proteins, is part of a multi-faceted approach to combating drug-resistant bacteria.