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

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

Sugar Rush in Research

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

Bacterial Biofilms: A Charged Environment

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 ‘Fight Clubs’ and the Search for New Medicines

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

Nature’s Medicine Cabinet

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

Elements That Keep Us Alive Also Give Color to Fireworks

Looking up at the night sky this Fourth of July, you might wonder what gives fireworks their vivid colors. The bright hues result from chemical elements that are also essential for life. Chemists and other researchers have been uncovering their roles in a range of important biological processes.

By mass, about 96 percent of our bodies are made of four key elements: oxygen (65 percent), carbon (18.5 percent), hydrogen (9.5 percent) and nitrogen (3.3 percent). These elements do not give color to fireworks, but they are found in our body’s most abundant and important molecules, including water, proteins and DNA.

A dozen or so other elements—mostly metals—make up the remaining 4 percent. Present in minuscule amounts, these elements are involved in everything from transporting oxygen and releasing hormones to regulating blood pressure and maintaining bone strength. They also add a burst of color when put in to a fireworks recipe. Here are several examples. Continue reading

Designing Drugs That Kill Invasive Fungi Without Harming Humans

Top to bottom: Cryptococcus, Candida, Aspergillus, Pneumocystis
Invasive fungal infections kill more than 1 million people worldwide every year. Almost all of these deaths are due to fungi in one of these four groups. Credit: Centers for Disease Control and Prevention.

Invasive fungal infections—the kind that infect the bloodstream, lung and brain—are inordinately deadly. A big part of the problem is the lack of drugs that are both effective against the fungi and nontoxic to humans.

The situation might change in the future though, thanks to the work of a multidisciplinary research team led by chemist Martin Burke at the University of Illinois. For years, the team has focused on an antifungal agent called amphotericin B (AmB for short). Although impressively lethal to fungi, AmB is also notoriously toxic to human cells.

Most recently, the research team chemically modified the drug to create compounds that kill fungi, but don’t disrupt human cells. The scientists explain it all in the latest issue of Nature Chemical Biology.

Invasive fungal infections are so intractable because most antifungal drugs aren’t completely effective. Plus, fungi have a tendency to develop resistance to them. AmB is a notable exception. Isolated 50 years ago from Venezuelan dirt, AmB has evaded resistance and remains highly effective. Unfortunately, it causes side effects so debilitating that some doctors call it “ampho-terrible.” At high doses, it is fatal.

For decades, scientists believed that AmB molecules kill fungal cells by forming membrane-piercing pores, or ion channels, through which the cells’ innards leak out. Last year, Burke’s group overturned this well-established concept using evidence from nuclear magnetic resonance, chemistry and cell-based experiments. The researchers showed that AmB molecules assemble outside cells into lattice-like structures. These structures act as powerful sponges, sucking vital lipid molecules, called ergosterol, right out of the fungal cell membrane, destroying the cell. Continue reading

Unusual DNA Form May Help Virus Withstand Extreme Conditions

A, B and Z DNA.
DNA comes in three forms: A, B and Z. Credit: A-DNA, B-DNA and Z-DNA by Zephyris (Richard Wheeler) under CC BY-SA 3.0.

DNA researcher Rosalind Franklin Exit icon first described an unusual form of DNA called the A-form in the early 1950s (Franklin, who died in 1958, would have turned 95 next month). New research on a heat- and acid-loving virus has revealed surprising information about this DNA form, which is one of three known forms of DNA: A, B and Z.

“Many people have felt that this A-form of DNA is only found in the laboratory under very non-biological conditions, when DNA is dehydrated or dry,” says Edward Egelman Exit icon in a University of Virginia news release Exit icon about the recent study. But considered with earlier studies on bacteria by other researchers, the new findings suggest that the A-form “appears to be a general mechanism in biology for protecting DNA.” Continue reading

Mapping Our Skin’s Microbes and Molecules

Last month, we shared some facts about the microbes that inhabit us. Here’s another: From head to toe, our skin bacteria coexist with chemicals in hygiene products, fibers from clothes and proteins shed by dead or dying skin cells.

These images highlight the complex composition of our body’s largest organ. They show the association between microbial diversity (top images) and skin chemistry (middle images). The different colors note the abundance of a certain bacterium or molecule—red is high, and blue is low. The skin maps remind NIH Director Francis Collins of a 60’s rock album cover. Continue reading

Field Focus: Making Chemistry Greener

Bob Lees
NIGMS’ Bob Lees answers questions about green chemistry. Credit: National Institute of General Medical Sciences.

Chemists funded by NIGMS are working to develop “greener” processes for discovering, developing and manufacturing medicines and other molecules with therapeutic potential, as well as compounds used in biomedical research. One of our scientific experts, organic chemist Bob Lees, recently spoke to me about some of these efforts.

What is green chemistry?

Green chemistry is the design of chemical processes and products that are more environmentally friendly. Among the 12 guiding principles of green chemistry Exit icon are producing less waste, including fewer toxic byproducts; using more sustainable (renewable) or biodegradable materials; and saving energy. Continue reading