Over the years, scientists have discovered many compounds in nature that have led to the development of medications. For instance, the molecular structure for aspirin came from willow tree bark, and penicillin was found in a type of mold. And uses of natural products aren’t limited to medicine cabinet staples and antibiotics. A cancer drug was originally found in the bark of the Pacific yew tree, and a medication for chronic pain relief was first isolated from cone snail venom. Today, NIGMS supports scientists in the earliest stages of investigating natural products made by plants, fungi, bacteria, and animals. The results could inform future research and bring advances to the field of medicine.Continue reading “Exploring Nature’s Treasure Trove of Helpful Compounds”
Tag: Cool Tools/Techniques
Most of us know helium as the gas that makes balloons float, but the second element on the periodic table does much more than that. Helium pressurizes the fuel tanks in rockets, helps test space suits for leaks, and is important in producing components of electronic devices. Magnetic resonance imaging (MRI) machines that take images of our internal organs can’t function without helium. And neither can nuclear magnetic resonance (NMR) spectrometers that researchers use to determine the structures of proteins—information that’s important in the development of medications and other uses.
Whether animals are looking for food or mates, or avoiding pathogens and predators, they rely on biosensors—molecules that allow them to sense and respond to their environments. Christina Dawn Smolke, Ph.D. , a professor of bioengineering at Stanford University in California, focuses her research on creating new kinds of biosensors to receive, process, and transmit molecular information. Her lab has built RNA molecules, or switches, that can alter gene expression based on biochemical changes they detect.Continue reading “Scientist Interview: Exploring the Promise of RNA Switches with Christina Dawn Smolke”
What Is Computer Modeling and How Does It Work?
Recent news headlines are awash in references to “modeling the spread” and “flattening the curve.” You may have wondered what exactly this means and how it applies to the COVID-19 pandemic. Infectious disease modeling is part of the larger field of computer modeling. This type of research uses computers to simulate and study the behavior of complex systems using mathematics, physics, and computer science. Each model contains many variables that characterize the system being studied. Simulation is done by adjusting each of the variables, alone or in combination, to see how the changes affect the outcomes. Computer modeling is used in a wide array of applications, from weather forecasting, airplane flight simulation, and drug development to infectious disease spread and containment.Continue reading “The Science of Infectious Disease Modeling”
A team of bioengineers, funded in part by NIGMS, has devised a way to use 3D bioprinting technology to construct the small air sacs in the lungs and intricate blood vessels. Continue reading “Advances in 3D Printing of Replacement Tissue”
You’ve probably heard news stories and other talk about CRISPR. If you’re not a scientist—well, even if you are—it can seem a bit complex. Here’s a brief recap of what it’s all about.
In 1987, scientists noticed weird, repeating sequences of DNA in bacteria. In 2002, the abbreviation CRISPR was coined to describe the genetic oddity. By 2006, it was clear that bacteria use CRISPR to defend themselves against viruses. By 2012, scientists realized that they could modify the bacterial strategy to create a gene-editing tool. Since then, CRISPR has been used in countless laboratory studies to understand basic biology and to study whether it’s possible to correct faulty genes that cause disease. Here’s an illustration of how the technique works.
Suppose you were a police detective investigating a robbery. You’d appreciate having a stack of photographs of the crime in progress, but you’d be even happier if you had a detailed movie of the robbery. Then, you could see what happened and when. Research on cells is somewhat like this. Until recently, scientists could take snapshots of cells in action, but they had trouble recording what cells were doing over time. They were getting an incomplete picture of the events occurring in cells.
Researchers have started solving this problem by combining some old knowledge—that DNA is spectacularly good at storing information—with a popular new research tool called CRISPR. CRISPR (clustered regularly interspaced short palindromic repeats) is an immune system feature in bacteria that helps them to remember and destroy viruses that infect them. CRISPR can change DNA sequences in precise ways; and it’s programmable, meaning that researchers can tell CRISPR where to make a change on a DNA strand, and even what kind of change to make. By linking cellular events to CRISPR, researchers can make something like a movie that captures many pieces of information in the form of DNA changes that researchers can read back later. These pieces of information include timing, duration, and intensity of events, such as the turning on of a specific protein pathway or the exposure of the cell to pathogens (i.e. germs). Here, we look at some of the ways NIGMS-funded research teams and others are using CRISPR to capture these kinds of data within DNA sequences.
Round and Round: mSCRIBE Creates a Continuous Recording Loop
CRISPR uses an enzyme called Cas9 like a surgical knife, to slice both strands of a cell’s DNA at precise points. A cut like this sends the cell scrambling to repair the damage. Often, the repair effort results in changes, or errors, in the repaired strand that pile up at a known rate. Timothy Lu and his colleagues at the Massachusetts Institute of Technology (MIT) decided to turn this cut-repair-error system into a way to record certain events inside a cell. They call their method mSCRIBE (mammalian synthetic cellular recorder integrating biological events).
Imagine if scientists could zap a single cell (or group of cells) with a pulse of light that makes the cell move, or even turns on or off the cell’s vital functions.
Scientists are working toward this goal using a technology called optogenetics. This tool draws on the power of light-sensitive molecules, called opsins and cryptochromes, which are naturally occurring molecules found in the cell membranes of a wide variety of species, from microscopic bacteria and algae to plants and humans. These light-reacting molecules change their shape or activity when they sense light, so they can be used to trigger cellular activity, such as turning on or off ion flow into the cell and other regulatory pathways. The ability to induce changes in cells has a broad range of practical applications, from enabling scientists to see how cells function to providing the basis for potential therapeutic applications for blindness, cancer, and epilepsy.
Opsins first gained a foothold in research about a decade ago when scientists began using them to study specific electrical networks in the brain. This research relied on channelrhodopsins, opsins that could be used to control the flow of charged ions into and out of the cell. Normally, when a neuron reaches a certain ion concentration, it is triggered to fire, but neuron firing can be changed by inserting opsins in the membrane. Neuroscientists figured out how to incorporate light-sensitive opsin proteins by inserting the opsin gene into the host’s DNA. The genetically encoded opsin proteins in the neuronal membranes could be turned on or off by shining light into the brain itself, using optical fibers or micro-LEDs, to switch on or off the flow of ions and neuron firing.
Since those early studies in the brain, the optogenetics field has come a long way. But the leap from brain cells to other cells has been challenging. Scientists first needed to find a way to deliver light into tissues deep in the body. And, unlike stationary brain cells, they needed a way to target cells that are on the move (such as immune cells). They also needed to develop a way to study not only cell networks but also individual cells and cell parts. The NIGMS-funded researchers highlighted below are among the scientists working to overcome these obstacles and are using optogenetics in new and inventive ways.
Yubin Zhou of Texas A&M is using optogenetics to control the way cells communicate and to study immune cell function. In one line of research, Zhou is using light to make it easier for calcium ions to enter cells. The ions carry instructions for the cell and also help tether small cellular structures (called organelles). Those inter-membrane tethers allow for the movement of proteins and lipids back and forth across the cell, and are critical for sending chemical messengers to communicate information (see illustration). When this process is disrupted, it can lead to extreme changes in cell function and even cell death. Using this technology to “switch on” normal pathways enables the scientists to better understand how such processes can be disrupted.
According to a recent estimate, implant infections following hip and knee replacement surgeries in the U.S. may number 65,000 by 2020, with the associated healthcare costs exceeding $1 billion. A new small, high-tech device could have a significant impact on improving health outcomes and reducing cost for these types of surgeries. The device, Air Barrier System (ABS), attaches on top of the surgical drape and gently emits HEPA-filtered air over the incision site. By creating a “cocoon” of clean air, the device prevents airborne particles—including the bacteria that can cause healthcare-associated infections—from entering the wound.
Scientists recently analyzed the effectiveness of the ABS device in a clinical study —funded by NIGMS—involving nearly 300 patients. Each patient needed an implant, such as an artificial hip, a blood vessel graft in the leg or a titanium plate in the spine. Because implant operations involve inserting foreign materials permanently into the body, they present an even higher risk of infection than many other surgeries, and implant infections can cause life-long problems.
The researchers focused on one of the most common causes of implant infections—the air in the operating room. Although operating rooms are much cleaner than almost any other non-hospital setting, it’s nearly impossible to sterilize the entire room. Instead, the scientists focused on reducing contaminants directly over the surgical site. They theorized that if the air around the wound was cleaner, the number of implant infections might go down. Continue reading “New Technology May Help Reduce Serious and Costly Post-Surgical Infections—Using Nothing but Air”
Cell biologists would love to shrink themselves down and actually see, touch and hear the inner workings of cells. Because that’s impossible, they have developed an ever-growing collection of microscopes to study cellular innards from the outside. Using these powerful tools, researchers can exhaustively inventory the molecular bits and pieces that make up cells, eavesdrop on cellular communication and spy on cells as they adapt to changing environments.
In recent years, scientists have developed new cellular imaging techniques that allow them to visualize samples in ways and at levels of detail never before possible. Many of these techniques build upon the power of electron microscopy (EM) to see ever smaller details.
Unlike traditional light microscopy, EM uses electrons, not light, to create an image. To do so, EM accelerates electrons in a vacuum, shoots them out of an electron gun and focuses them with doughnut-shaped magnets onto a sample. When electrons bombard the sample, some pass though without being absorbed while others are scattered. The transmitted electrons land on a detector and produce an image, just as light strikes a detector (or film) in a camera to create a photograph.
Transmission electron microscopes can magnify objects more than 10 million times, enabling scientists to see the outline and some details of cells, viruses and even some large molecules. A relatively new form of transmission electron microscopy called cryo-EM enables scientists to view specimens in their natural or near-natural state without the need for dyes or stains.
In cryo-EM—the prefix cry- means “cold” or “freezing”—scientists freeze a biological sample so rapidly that water molecules do not have time to form ice crystals, which could shove cellular materials out of their normal place. Cold samples are more stable and can be imaged many times over, allowing researchers to iteratively refine the image, remove artifacts and produce even sharper images than ever before. Continue reading “Cool Tools: Pushing the Limits of High-Resolution Microscopy”