Interview With a Scientist: Unlocking the Secrets of Animal Regeneration With Alejandro Sánchez Alvarado

Most of what we know comes from intensive study of research organisms—mice, fruit flies, worms, zebrafish, and a few others. But according to Alejandro Sánchez Alvarado Link to external web site, a researcher at the Stowers Institute for Medical Research in Kansas City and a Howard Hughes Medical Institute Investigator, these research organisms represent only a tiny fraction of all animal species on the planet. Under-studied organisms could reveal important biological phenomena that simply don’t occur in the handful of models typically studied, he says.

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RNA Polymerase: A Target for New Antibiotic Drugs?

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.

RNAP illustrated as a crab claw, clamping on a DNA double helix. Artist interpretation of RNAP grasping and unwinding a DNA double helix. Credit: Wei Lin and Richard H. Ebright.

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.

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Computational Biologist Melissa Wilson on Sex Chromosomes, Gila Monsters, and Career Advice

Melissa Wilson wearing a floral dress and speaking beside a podium during her lecture. Dr. Melissa Wilson.
Credit: Chia-Chi Charlie Chang.

The X and Y chromosomes, also known as sex chromosomes, differ greatly from each other. But in two regions, they are practically identical, said Melissa Wilson Link to external web site, assistant professor of genomics, evolution, and bioinformatics at Arizona State University.

“We’re interested in studying how the process of evolution shaped the X and the Y chromosome in gene content and expression and how that subsequently affects literally everything else that comes with being a human,” she said at the April 10 NIGMS Director’s Early-Career Investigator (ECI) Lecture at NIH.

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Amazing Organisms and the Lessons They Can Teach Us

What do you have in common with rodents, birds, and reptiles? A lot more than you might think. These creatures have organs and body systems very similar to our own: a skeleton, digestive tract, brain, nervous system, heart, network of blood vessels, and more. Even so-called “simple” organisms such as insects and worms use essentially the same genetic and molecular pathways we do. Studying these organisms provides a deeper understanding of human biology in health and disease, and makes possible new ways to prevent, diagnose, and treat a wide range of conditions.

Historically, scientists have relied on a few key organisms, including bacteria, fruit flies, rats, and mice, to study the basic life processes that run bodily functions. In recent years, scientists have begun to add other organisms to their toolkits. Many of these newer research organisms are particularly well suited for a specific type of investigation. For example, the small, freshwater zebrafish grows quickly and has transparent embryos and see-through eggs, making it ideal for examining how organs develop. Organisms such as flatworms, salamanders, and sea urchins can regrow whole limbs, suggesting they hold clues about how to improve wound healing and tissue regeneration in humans.

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CRISPR Illustrated

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.

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Interview With a Scientist—Julius Lucks: Shape Seeker

While DNA acts as the hard drive of the cell, storing the instructions to make all of the proteins the cell needs to carry out its various duties, another type of genetic material, RNA, takes on a wide variety of tasks, including gene regulation, protein synthesis, and sensing of metals and metabolites. Each of these jobs is handled by a slightly different molecule of RNA. But what determines which job a certain RNA molecule is tasked with? Primarily its shape. Julius LucksLink to external web site, a biological and chemical engineer at Northwestern University, and his team study the many ways in which RNA can bend itself into new shapes and how those shapes dictate the jobs the RNA molecule can take on.

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Best Documentary: Cells Record Their Own Lives Using CRISPR

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.

Left: Rectangle containing magnetic tape illustrated as a black strip wound on two spools. Closeup of the magnetic tape beneath as a blue strip with orange lines to indicate stored audio signals. Text reads: data in magnetic tape. Center: Four, white capsule-shaped bacteria, with three rows of connected shapes (black diamonds, blue and orange rectangles) beneath to illustrate stored biological signals in bacteria. Text reads: data in CRISPR tape in cells. Right: Numerous capsule-shaped bacteria in different colors, each containing a black strip wound on two spools

An audio recorder stores audio signals into a magnetic tape medium (left). Similarly, a microscopic data recorder stores biological signals into a CRISPR tape in bacteria (middle). An enormous amount of information can be stored across multiple bacterial cells (right). Credit: Wang Lab/Columbia University Medical Center.

Round and Round: mSCRIBE Creates a Continuous Recording Loop

A dark blue-green cell with textured surface containing a round, blue meter with a white dial. The dial reads a magenta ribbon of DNA and records over time the number of cellular events that occur. The cellular events are depicted by purple, green, and smaller magenta clusters moving through the cell.
MIT bioengineers, led by Timothy Lu, have devised a memory storage system illustrated here as a DNA-embedded meter that records the activity of a signaling pathway in a human cell. Credit: Timothy Lu lab, MIT.

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 Link to external web site 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).

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Interview with a Scientist: Jeramiah Smith on the Genomic Antics of an Ancient Vertebrate

The first known descriptions of cancer come from ancient Egypt more than 3,500 years ago. Early physicians attributed the disease to several factors, including an imbalance in the body’s humoral fluids, trauma, and parasites. Only in the past 50 years or so have we figured out that mutations in critical genes are often the trigger. The sea lamprey, a slimy, snake-like blood sucker, is proving to be an ideal tool for understanding these mutations.

The sea lamprey, often called the jawless fish, is an ancient vertebrate whose ancestor diverged from the other vertebrate lineages (fish, reptiles, birds and mammals) more than 500 million years ago. Jeramiah Smith,Link to external web site associate professor of biology at the University of Kentucky, has discovered that lamprey have two separate genomes: a complete genome specific to their reproductive cells, consisting of 99 chromosomes (humans have 23 pairs) and another genome in which about 20 percent of genes have been deleted after development. Using the lamprey model, Smith and his colleagues have learned that many of these deleted genes—such as those that initiate growth pathways—are similar to human oncogenes (i.e., cancer-causing genes).

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