Inside our bodies is a surprising amount of metal. Not enough to set off the scanners at the airport or make us rich, but enough to fill each of our cells with billions of metal ions, including calcium, iron, copper and zinc. These ions facilitate critical biological functions. However, too much of any metal can be toxic, while too little can cause disease. Our cells carefully monitor and control their metal content using a whole series of proteins that bind, sense and transport metal ions. Keeping tabs on why and how metals flow into and out of our cells is a passion of Thomas O’Halloran , professor of chemistry and molecular biosciences at Northwestern University in Illinois. For the past three decades, O’Halloran has investigated how fluctuations in the amount of metal ions inside cells influence gene expression, cell growth and other vital functions. Using a variety of approaches, he has uncovered new types of proteins that bind metal ions and investigated the role that imbalances in these ions play in a number of disease-related physiological processes. One recent focus of his studies has been how zinc regulates oocyte (egg cell) maturation and fertilization. Ultimately, his work could help us better understand infertility, cancer and certain bacterial infections.

Have you ever collected coins, cards, toy trains, stuffed animals? Did you feel the need to complete the set? If so, then you may be a completist. A completist will go to great lengths to acquire a complete set of something. Scientists can also be completists who are inspired to identify and catalog every object in a particular field to further our understanding of it. For example, a comprehensive parts list of the human body—and of other organisms that are important in biomedical research—could aid in the development of novel treatments for diseases in the same way that a parts list for a car enables auto mechanics to build or repair a vehicle. More than 15 years ago, scientists figured out how to catalog every gene in the human body. In the years since, rapid advances in technology and computational tools have allowed researchers to begin to categorize numerous aspects of the biological world. There’s actually a special way to name these collections: Add “ome” to the end of the class of objects being compiled. So, the complete set of genes in the body is called the “genome,” and the complete set of proteins is called the “proteome.” Below are three -omes that NIH-funded scientists work with to understand human health. Genome The genome is the original -ome. In 1976, Belgium scientists identified all 3,569 DNA bases—the As, Cs, Gs and Ts that make up DNA’s code—in the genes of bacteriophage MS2, immortalizing this bacteria-infecting virus as possessing the first fully sequenced genome. Over the next two decades, a small handful of additional genomes from other microorganisms followed. The first animal genome was completed in 1998. Just 5 years later, scientists identified all 3.2 billion DNA bases in the human genome, representing the work of more than 1,000 researchers from six countries over a period of 13 years.

An exhibit called “Minerals in Medicine” opened at the NIH Clinical Center last month (see slideshow). The display features a fascinating overview of how dozens of minerals are used to create drugs and medical instruments useful in treating disease and maintaining health. The minerals ranged from commonplace ones like quartz, which is used to make medical instruments, to more exotic ones like hubnerite, a source of the metal tungsten, which is used in radiation shielding.

Inspired by this collection, which is co-sponsored by NIH and the Smithsonian Institution, we highlight here examples of “Metals in Medicine.”

Copper and Fat Metabolism

What does a metal like copper have to do with our ability to breakdown fat? Researchers explored this question by observing mice with Wilson’s disease—a rare, inherited condition that causes copper to accumulate in the liver, brain and other vital organs. The mice with the condition usually have larger deposits of fat compared to healthy mice. To confirm that fat metabolism is somehow compromised in these mice, the researchers treated them with a drug that induces the breakdown of fat. And indeed they found that less fat was metabolized in mice with the disease.

In an effort to investigate what role copper may be playing in fat metabolism, the researchers examined adipose tissue, or fat, cells under a microscope to track the metal’s interactions with various proteins in the cell. They discovered that copper inhibits an enzyme called PDE3. This enzyme usually prevents another enzyme called cAMP from helping to break down fat. The researchers concluded that copper actually promotes fat metabolism. This work shows that transition metal nutrients can play signaling roles, which has been previously thought to be restricted to alkali and alkaline earth metals like sodium, potassium and calcium.

This Halloween, you’re not likely to see many trick-or-treaters dressed as spiders. Google Trends pegs “Spider” as the 87th most searched-for Halloween costume, right between “Hippie” and “The Renaissance.” But don’t let your guard down. Spiders are everywhere.

More than 46,000 species of spiders creepy crawl across the globe, on every continent except Antarctica. Each species produces a venom composed of an average of 500 distinct toxins, putting the conservative estimate of unique venom compounds at more than 22 million. This staggering diversity of venoms, collectively referred to as the venome, has only begun to be explored.

The outside of every cell on Earth—from the cells in your body to single-celled microorganisms—is blanketed with a coat of carbohydrates, or sugar molecules, that extend from the cell surface, branching off and bending as they interface with the extra-cellular space. The specific patterns in which these carbohydrates are arranged serve as an ID code that help cells recognize each other. For example, human liver cells have one pattern, while human red blood cells another. Certain diseases can even alter the pattern of surface carbohydrates, which is one way the body can recognize damaged cells. On foreign cells, including invading bacteria such as Streptococcus pneumoniae, the carbohydrate coat is even more distinct. Laura Kiessling, a professor of chemistry at the University of Wisconsin, Madison, studies how carbohydrate coats are assembled and how cells use these coats to tell friend from foe. The implications of her research suggest strategies for targeting tumors, fighting diseases of inflammation and, as she discusses in this video, developing new classes of antibiotics.

When Margaret Sedensky, now of Seattle Children’s Research Institute, started as an anesthesiology resident, she wasn’t entirely clear on how anesthetics worked. “I didn’t know, but I figured someone did,” she says. “I asked the senior resident. I asked the attending. I asked the chair. Nobody knew.” For many years, doctors called general anesthetics a “modern mystery.” Even though they safely administered anesthetics to millions of Americans, they didn’t know exactly how the drugs produced the different states of general anesthesia. These states include unconsciousness, immobility, analgesia (lack of pain) and amnesia (lack of memory). Understanding anesthetics has been challenging for a number of reasons. Unlike many drugs that act on a limited number of proteins in the body, anesthetics interact with seemingly countless proteins and other molecules. Additionally, some anesthesiologists believe that anesthetics may work through a number of different molecular pathways. This means no single molecular target may be required for an anesthetic to work, or no single molecular target can do the job without the help of others. “It’s like a symphony,” says Roderic Eckenhoff of the University of Pennsylvania Perelman School of Medicine, who has studied anesthesia for decades. “Each molecular target is an instrument, and you need all of them to produce Beethoven’s 5th.”

If you’ve ever felt a slimy coating on your teeth, scrubbed grime from around a sink drain or noticed something growing between the tiles of a shower, you’ve encountered a biofilm. Made up of communities of bacteria and other microorganisms, biofilms thrive where they can remain moist and relatively undisturbed. As they enlarge, biofilms can block narrow passages like medical stents, airways, pipes or intestines.

In a way, Janarthanan Jayawickramarajah is like an architect. But rather than sketching plans for homes or buildings, he creates molecules designed to detect and destroy cancer cells.

Simple sugars such as sucrose (found in the sugar bowl) and fructose (in fruits and honey) provide the sweet finishing touches on many holiday treats. But did you know that versions of these molecules also serve important functions in our cells? Cells assemble sugar molecules into chains known as glycans. These glycans, which can be linear or branching, play an astounding number of biological roles. When bound to proteins called lectins, they enable a fertilized egg to attach properly onto a woman’s uterine wall and help immune cells move out of a blood vessel to the site of an infection. When decorated with specific patterns of molecules called sulfates, glycans can help direct the growth of nerves. And it’s the glycans found on our blood cells that define blood type (A, B, AB or O).

Last summer, we shared findings from Gürol Süel and colleagues at the University of California, San Diego, that bacterial cells in tight-knit microbial communities called biofilms expand in a stop-and-go pattern. The researchers concluded that this pattern helps make food at the nutrient-rich margin available to the cells in the starved center, but they didn’t know how. They’ve now shown that the cells use electrochemical signaling to communicate and cooperate with each other. Because nutrients and other signals cells use to sense each other and their environment move rather slowly, the researchers looked for a faster, more active communication system in biofilms of the bacterium B. subtilis. They focused on electrical signaling via potassium, a positively charged ion that, for example, our nerve and muscle cells use to send or receive signals.