Category: Chemistry, Biochemistry and Pharmacology

Metals in Medicine

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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

Fluorescent imaging of copper in white fat cells from mice.

Fluorescent imaging of copper in white fat cells from mice. The left panel shows fat cells with normal levels of copper, and the right panel shows fat cells deficient in copper. Credit: Lakshmi Krishnamoorthy and Joseph Cotruvo Jr., University of California, Berkeley.

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.

Continue reading “Metals in Medicine”

Exploring the Evolution of Spider Venom to Improve Human Health

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Brown recluse

Female brown recluse spider. Credit Matt Bertone, North Carolina State University.

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.

“I grew up on a farm in Indiana and had the luxury of exploring and turning over rocks and being curious. Any feelings of being grossed out by spiders were rapidly replaced by my feelings of awe for how amazing and diverse these creatures are.”– Greta Binford”

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. Continue reading “Exploring the Evolution of Spider Venom to Improve Human Health”

Interview With a Scientist: Laura Kiessling, Carbohydrate Scientist

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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.

Demystifying General Anesthetics

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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).

Stock image of a symphony.
Like the instruments that make up an orchestra, many molecular targets may contribute to an anesthetic producing the desired effect. Credit: Stock image.

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.” Continue reading “Demystifying General Anesthetics”

Cool Video: Watching Bacteria Turn Virulent

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Researchers created an apparatus to study quorum sensing, a communication system that allows some bacteria to cause dangerous infections. Their findings suggest that blocking bacterial communication might lead to a new way to combat such infections. Credit: Minyoung Kevin Kim and Bonnie Bassler, Princeton University.

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. Continue reading “Cool Video: Watching Bacteria Turn Virulent”

Meet a Globe-Trotting Chemist and Builder of “Smart Molecules”

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Janarthanan Jayawickramarajah
Jayawickramarajah taking a “selfie” with “The Bean,”
a large, highly reflective sculpture in Chicago
Credit: Janarthanan Jayawickramarajah
Janarthanan Jayawickramarajah
Born in: Kandy, Sri Lanka
Job site: Tulane University, New Orleans, Louisiana
Alternate career choice: Anthropologist
Favorite sports teams: Sri Lanka national cricket team, University of North Carolina at Chapel Hill Tar Heels basketball, New Orleans Saints football
Favorite weekend activity: Strolling through parks with his wife and two kids and stopping for coffee and beignets (a New Orleans treat, a lot like a doughnut covered in powdered sugar)

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. Continue reading “Meet a Globe-Trotting Chemist and Builder of “Smart Molecules””

Sugar Rush in Research

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Cookies
Sugar sprinkled on cookies and other treats is often an attractive—and sweet tasting—finishing touch. But the sugar-rich coating that surrounds most cells is far more—it’s a vital ingredient for many basic cellular processes. Credit: Stock image.

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). Continue reading “Sugar Rush in Research”

Bacterial Biofilms: A Charged Environment

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Bacillus subtilis biofilm
A Bacillus subtilis biofilm grown in a Petri dish. Credit: Süel Lab, UCSD.

Last summer, we shared findings from Gürol Süel Exit icon 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. Continue reading “Bacterial Biofilms: A Charged Environment”

Bacterial ‘Fight Clubs’ and the Search for New Medicines

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Competition encourages bacteria to produce secondary metabolites with therapeutic potential that they would otherwise hold in reserve. Credit: Michael Smeltzer, Vanderbilt University.

Bacteria hold a vast reservoir of compounds with therapeutic potential. They use these compounds, known as secondary metabolites, to protect themselves against their enemies. We use them in many antibiotics, anti-inflammatories and other treatments.

Scientists interested in developing new medicines have no shortage of places to look for secondary metabolites. There are an estimated 120,000 to 150,000 bacterial species on Earth. Each species is capable of producing hundreds of secondary metabolites, but often only under specific ecological conditions. The challenge for researchers is figuring out how to coax the bacteria to produce these compounds.

Now, Brian Bachmann Exit icon and John McLean Exit icon of Vanderbilt University and their teams have shown that by creating “fight clubs” where bacteria compete with one another, they can trigger the bacteria to make a wide diversity of molecules, including secondary metabolites. Continue reading “Bacterial ‘Fight Clubs’ and the Search for New Medicines”

Nature’s Medicine Cabinet

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More than 70 percent of new drugs approved within the past 30 years originated from trees, sea creatures and other organisms that produce substances they need to survive. Since ancient times, people have been searching the Earth for natural products to use—from poison dart frog venom for hunting to herbs for healing wounds. Today, scientists are modifying them in the laboratory for our medicinal use. Here’s a peek at some of the products in nature’s medicine cabinet.

Vampire bat

A protein called draculin found in the saliva of vampire bats is in the last phases of clinical testing as a clot-buster for stroke patients. Vampire bats are able to drink blood from their victims because draculin keeps blood from clotting. The first phases of clinical trials have shown that the protein’s anti-coagulative properties could give doctors more time to treat stroke patients and lower the risk of bleeding in the brain.

Continue reading “Nature’s Medicine Cabinet”