Here are some images from our gallery that remind us of the winter holidays—and showcase important findings and innovations in biomedical research. Ribbons and Wreaths This wreath represents the molecular structure of a protein, Cas4, which is part of a system, known as CRISPR, that bacteria use to protect themselves against viral invaders. The green ribbons show the protein’s structure, and the red balls show the location of iron and sulfur molecules important for the protein’s function. Scientists have harnessed Cas9, a different protein in the bacterial CRISPR system, to create a gene-editing tool known as CRISPR-Cas9. Using this tool, researchers can study a range of cellular processes and human diseases more easily, cheaply and precisely. Last week, Science magazine recognized the CRISPR-Cas9 gene-editing tool as the “breakthrough of the year.”

We asked the heads of our scientific divisions to tell us about some of the big questions in fundamental biomedical science that researchers are investigating with NIGMS support. This article is the third in an occasional series that explores these questions and explains how pursuing the answers could advance understanding of important biological processes.

Researchers are on a quest to crack a code made by ubiquitin, a small protein that plays a big role in coordinating cellular function. By attaching to other proteins, ubiquitin determines what those proteins should do next.

Just as zip codes direct letters to specific towns, the ubiquitin code might direct one protein to help with DNA repair, another to assist in cell division, and a third to transport molecules into and out of cells.

Looking like necklaces stacked on a dresser, these bright, amorphous loops show the outlines of yeast proteins that make up the spindle pole, a cellular component found in organisms as diverse as yeast and humans. Each cell starts with a single spindle pole, which must somehow duplicate to form the pair that works together to pull matching chromosomes apart during cell division. Scientists don’t completely understand how this duplication occurs, but they do know that errors in spindle pole copying can lead to a number of health conditions, including cancer.

Has the “spring forward” time change left you feeling drowsy? While researchers can’t give you back your lost ZZZs, they are unraveling a long-standing mystery about sleep. Their work will advance the scientific understanding of the process and could improve ways to foster natural sleep patterns in people with sleep disorders.

Working at Massachusetts General Hospital and MIT, Christa Van Dort, Matthew Wilson, and Emery Brown focused on the stage of sleep known as REM. Our most vivid dreams occur during this period, as do rapid eye movements, for which the state is named. Many scientists also believe REM is crucial for learning and memory.

REM occurs several times throughout the night, interspersed with other sleep states collectively called non-REM sleep. Although REM is clearly necessary—it occurs in all land mammals and birds—researchers don’t really know why. They also don’t understand how the brain turns REM on and off.

Visualizations can give scientists unprecedented views of complex biological processes. Here’s a look at two new ones that shed light on how HIV enters host cells.

Animation of HIV’s Entry Into Host Cells

We previously introduced you to Janet Iwasa, a molecular animator who’s visualized complex biological processes such as cells ingesting materials and proteins being transported across a cell membrane. She has now released several animations from her current project of visualizing HIV’s life cycle . The one featured here shows the virus’ entry into a human immune cell.

"Janet's animations add great value by helping us consider how complex interactions between viruses and their host cells actually occur in time and space,” says Wes Sundquist, who directs the Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV at the University of Utah. "By showing us how different steps in viral replication must be linked together, the animations suggest hypotheses that hadn’t yet occurred to us.”

Whether aiding in early growth and development, ensuring a healthy nervous system or guarding the body from illness, zinc plays an important role in the human body.

Husband-and-wife team, Thomas O’Halloran and Teresa Woodruff, plus other researchers at Northwestern University, evaluated the role that zinc plays in healthy fertilization. The study revealed how mouse eggs gather and release billions of zinc atoms at once in events called zinc sparks. These fluxes in zinc concentration are essential in regulating the biochemical processes that facilitate the egg-to-embryo transition.

The scientists developed a series of techniques to determine the amount and location of zinc atoms during an egg cell’s maturation and fertilization as well as in the following two hours. Special imaging methods allowed the researchers to also visualize the movement of zinc sparks in three dimensions.

Scientists may screen billions of chemical compounds before uncovering the few that effectively treat a disease. But identifying compounds that work is just the first step toward developing a new therapy. Scientists then have to determine exactly how those compounds function.

Different cancer therapies attack cancer cells in distinct ways. For example, some drugs kill cancer cells by causing their outer membranes to rapidly rupture in a process known as necrosis. Others cause more subtle changes to cell membranes, which result in a type of programmed cell death known as apoptosis.

If researchers could distinguish the membrane alterations of chemically treated cancer cells, they could quickly determine how that chemical compound brings about the cells’ death. A new sensor developed by a research team led by Vincent Rotello of the University of Massachusetts Amherst can make these distinctions in minutes.

This time of year, lights brighten our homes and add sparkle to our holidays. Year-round, scientists funded by the National Institutes of Health use light to illuminate important biological processes, from the inner workings of cells to the complex activity of the brain. Here’s a look at just a few of the ways new light-based tools have deepened our understanding of living systems and set the stage for future medical advances. Visualizing Viral Activity What looks like a colorful pattern produced as light enters a kaleidoscope is an image of a cell infected with respiratory syncytial virus (RSV) lit up by a new fluorescent probe called MTRIPS (multiply labeled tetravalent RNA imaging probes). Although relatively harmless in most children, RSV can lead to bronchitis and pneumonia in others. Philip Santangelo of the Georgia Institute of Technology and Emory University, along with colleagues nationwide, used MTRIPS to gain a closer look at the life cycle of this virus. Once introduced into RSV-infected cells, MTRIPS latched onto the genetic material of individual viral particles (in the image, red), making them glow. This enabled the researchers to follow the entry, assembly and replication of RSV inside the living cells.

Much as a photographer brings distant objects into focus with a telephoto lens, scientists can now see previously indistinct cellular components as small as a few billionths of a meter (nanometers). By overcoming some of the limitations of conventional optical microscopy, a set of techniques known as super-resolution fluorescence microscopy has changed once-blurry images of the nanoworld into well-resolved portraits of cellular architecture, with details never seen before in biology. Reflecting its importance, super-resolution microscopy was recognized with the 2014 Nobel Prize in chemistry. Using the new techniques, scientists can observe processes in living cells across space and time and study the movements, interactions and roles of individual molecules. For instance, they can identify and track the proteins that allow a virus to invade a cell or those that enable tumor cells to migrate to distant parts of the body in metastatic cancer. The ability to analyze individual molecules, rather than collections of molecules, allows scientists to answer longstanding questions about cellular mechanisms and behavior, such as how cells move along a surface or how certain proteins interact with DNA to regulate gene activity.

Each fluorescent point of light making up the multicolored rings in this image is an individual human embryonic cell in the early stages of development. Scientists seeking to understand the molecular cues responsible for early embryonic patterning found that human embryonic cells confined to areas of precisely controlled size and shape begin to specialize, migrate and organize into distinct layers just as they would under natural conditions. Read the Inside Life Science article to learn more about this research, which has opened a new window for studying early development and could advance efforts aimed at using human stem cells to replace diseased cells and regenerate lost or injured body parts.