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”
Sepsis is a serious medical condition caused by an overwhelming response to infection that damages tissues and organs. It’s unpredictable, progresses quickly, can strike anyone, and is a leading cause of hospital-related deaths. In the U.S. alone, nearly 270,000 people die each year from sepsis. Those who survive sepsis often end up in the hospital again, and some have long-term health complications. Early treatment is key for many patients to survive sepsis, yet doctors can’t easily diagnose it because it’s so complex and each patient is different.
Despite decades of research, sepsis remains a poorly understood condition with limited diagnostic tools and treatment. To tackle these obstacles, scientists Vincent Liu, Christopher Seymour, and Hallie Prescott have started using a “big data” approach, which relies on complex computer programs to sift through huge amounts of information. In this case, the computers analyze data such as demographic information, vital signs, and routine blood tests in the electronic health records of sepsis patients. The goal is to find patterns in the data that might help doctors understand, predict, and treat sepsis more effectively.Continue reading “Sepsis: Using Big Data to Cut a Killer Down to Size”
Research on how diet impacts the gut microbiota has rapidly expanded in the last several years. Studies show that diets rich in red meat are linked to diseases such as colon cancer and heart disease. In both mice and humans, researchers have recently discovered differences in the gut microbiota of those who eat diets rich in red meat compared with those who don’t. This is likely because of a sugar molecule in the red meat, called N-glycolylneuraminic acid (Neu5Gc), that our bodies can’t break down. Researchers believe the human immune system sees Neu5Gc as foreign. This triggers the immune system, causing inflammation in the body, and possibly leads to disease over time.Continue reading “The Meat of the Matter: Learning How Gut Microbiota Might Reduce Harm from Red Meat”
DNA, with its double-helix shape, is the stuff of genes. But genes themselves are only “recipes” for protein molecules, which are molecules that do the real heavy lifting (or do much of the work) inside cells.
Here’s how it works. A molecular machine called RNA polymerase (RNAP) travels along DNA to find a place where a gene begins. RNAP uses a crab-claw-like structure to grasp and unwind the DNA double helix at that spot. RNAP then copies (“transcribes”) the gene into messenger RNA (mRNA), a molecule similar to DNA.
The mRNA molecule travels to one of the cell’s many protein-making factories (ribosomes), which use the mRNA message as instructions for making a specific protein.Continue reading “RNA Polymerase: A Target for New Antibiotic Drugs?”
A. The Postbaccalaureate Research Education Program (PREP) at the Sackler School of Graduate Biomedical Sciences at Tufts University in Boston.Continue reading “PREP Scholar’s Passion for Understanding Body’s Defenses”
Cataloging the human microbiome—the complete collection of bacteria, fungi, archaea, protists, and viruses that live in and on our bodies—is an enormous task. Most estimates put the number of organisms who call us home on par with the number of our own cells. Imagine trying to figure out how the billions of critters influence each other and, ultimately, impact our health. Elhanan Borenstein, a computer scientist-cum-genomicist at the University of Washington, and his team are not only tackling this difficult challenge, they are also trying to obtain a systems-level understanding of the collective effect of all of the genes, proteins, and metabolites produced by the numerous species within the microbiome.
You’ve likely heard some variation of the statistic that there are at least as many microbial cells in our body as human cells. You may have also heard that the microscopic bugs that live in our guts, on our skins, and every crevice they can find, collectively referred to as the human microbiome, are implicated in human health. But do these bacteria, fungi, archaea, protists, and viruses cause disease, or are the specific populations of microbes inside us a result of our state of health? That’s the question that drives the research in the lab of Andrew Goodman , associate professor of microbial pathogenesis at Yale University.
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).
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.
Every one of our thoughts, emotions, sensations, and movements arise from changes in the flow of electricity in the brain. Disruptions to the normal flow of electricity within and between cells is a hallmark of many diseases, especially neurological and cardiac diseases.
The source of electricity within nerve cells (i.e., neurons) is the separation of charge, referred to as voltage, across neuronal membranes. In the past, scientists weren’t able to identify all the molecules that control neuronal voltage. They simply lacked the tools. Now, University of Colorado biologist Joel Kralj has developed a way to overcome this hurdle. His new technique—combining automated imaging tools and genetic manipulation of cells—is designed to measure the electrical contribution of every protein coded by every gene in the human genome. Kralj believes this technology will usher in a new field of “electromics” that will be of enormous benefit to both scientists studying biological processes and clinicians attempting to treat disease.
In 2017, Kralj won a New Innovator Award from the National Institutes of Health for his work on studying voltage in neurons. He is using the grant money to develop a new type of microscope that will be capable of measuring neuronal voltage from hundreds of cells simultaneously. He and his research team will then attempt to identify the genes that encode any of the 20,000 proteins in the human body that are involved in electrical signaling. This laborious process will involve collecting hundreds of nerve cells, genetically removing a single protein from each cell, and using the new microscope to see what happens. If the voltage within a cell is changed in any way when a specific protein is removed, the researchers can conclude that the protein is essential to electrical signaling.
In this video, Kralj discusses how he plans to use his electromics platform to study electricity-generating cells throughout the body, as well as in bacterial cells (see our companion blog post “Feeling Out Bacteria’s Sense of Touch” featuring Kralj’s research for more details).
Dr. Kralj’s work is funded in part by the NIH under grant 1DP2GM123458-01.