Over the past 12 months, we’ve explored a variety of topics in genetics, cell biology, chemistry, and careers in the biomedical sciences. As we ring in the new year, we bring you our top three posts of 2019. If your favorite is missing, let us know what it is in the comments section below!
Hawaiian bobtail squid. Credit: Dr. Satoshi Shibata.
Studying research organisms, such as those featured in this post, teaches us about ourselves. These amazing creatures, which have some traits similar to our own, may hold the key to preventing and treating an array of complex diseases.
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 , 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.
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.
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.
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 , assistant professor of genomics, evolution, and bioinformatics at Arizona State University.
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.
Women have two X chromosomes (XX) and men have one X and one Y (XY), right? Not always, as you’ll learn from the quiz below. Men can be XX and women can be XY. And many other combinations of X and Y are possible.
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.
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 Lucks, 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.
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.
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
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 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).