Category: Chemistry, Biochemistry and Pharmacology

Designing Drugs That Kill Invasive Fungi Without Harming Humans

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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 “Designing Drugs That Kill Invasive Fungi Without Harming Humans”

Unusual DNA Form May Help Virus Withstand Extreme Conditions

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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 “Unusual DNA Form May Help Virus Withstand Extreme Conditions”

Preventing Sepsis in Half the Time

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Human digestive system
A new study suggests that an antibiotic regimen half as long as the standard course could be just as effective in treating intra-abdominal infections and preventing sepsis. Credit: Stock image.

When treating infections, the most critical actions are to quash the infection at its site of origin and prevent it from spreading. If allowed to spread to the bloodstream, an infection could result in body-wide inflammation known as sepsis that can cause organ failure and death.

Intra-abdominal infections, most often caused by gut bacteria, can lead to painful inflammation and present a high risk for sepsis. These infections, which include appendicitis, are some of the most common illnesses around the world.

A standard treatment regimen includes surgically removing the original infection and then prescribing antibiotics to keep the infection from coming back and to prevent sepsis. Currently, doctors administer antibiotics until 2 days after the symptoms disappear, for a total of up to 2 weeks.

Like many other researchers, University of Virginia’s Robert Sawyer Exit icon wondered if treating intra-abdominal infections with shorter antibiotic courses could be just as effective as the standard treatment. To find out, he and a team of researchers from around the country designed the Study to Optimize Peritoneal Infection Therapy (STOP-IT). Continue reading “Preventing Sepsis in Half the Time”

Mapping Our Skin’s Microbes and Molecules

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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 “Mapping Our Skin’s Microbes and Molecules”

Field Focus: Making Chemistry Greener

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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 “Field Focus: Making Chemistry Greener”

Scientists Shine Light on What Triggers REM Sleep

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Illustration of a brain.
While studying how the brain controls REM sleep, researchers focused on areas abbreviated LDT and PPT in the mouse brainstem. This illustration shows where these two areas are located in the human brain. Credit: Wikimedia Commons. View larger image

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.

Continue reading “Scientists Shine Light on What Triggers REM Sleep”

Zinc’s Role in Healthy Fertilization

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Screen shot of the video
Fluorescent sensors at the cell surface show zinc-rich packages being released from the egg during fertilization. Credit: Northwestern Visualization.

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 Exit icon 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.

Continue reading “Zinc’s Role in Healthy Fertilization”

Remotely and Noninvasively Controlling Genes and Cells in Living Animals

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Remote control car key.
Researchers are developing a system to remotely control genes or cells in living animals with radio wave technology similar to that used to operate remote control car keys. Credit: Stock image.

One of the items on biomedical researchers’ “to-do” list is devising noninvasive ways to control the activity of specific genes or cells in order to study what those genes or cells do and, ultimately, to treat a range of human diseases and disorders.

A team of scientists recently reported progress on a new, noninvasive system that could remotely and rapidly control biological targets in living animals. The system can be activated remotely using either low-frequency radio waves or a magnetic field. Similar radio wave technology operates automatic garage-door openers and remote control car keys and is used in medicine to control electronic pacemakers noninvasively. Magnetic fields are used to activate sensors in burglar alarm systems and to turn your laptop to hibernate mode when the cover is closed. Continue reading “Remotely and Noninvasively Controlling Genes and Cells in Living Animals”

Meet Maureen L. Mulvihill

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Maureen L. Mulvihill, Ph.D.
Credit: Actuated Medical, Inc.
Maureen L. Mulvihill, Ph.D.
Fields: Materials science, logistics
Works at: Actuated Medical, Inc., a small company that develops medical devices
Second job (volunteer): Bellefonte YMCA Swim Team Parent Boost Club Treasurer
Best skill: Listening to people
Last thing she does every night: Reads to her 7- and 10-year-old children until “one of us falls asleep”

If you’re a fan of the reality TV show Shark Tank, you tune in to watch aspiring entrepreneurs present their ideas and try to get one of the investors to help develop and market the products. Afterward, you might start to think about what you could invent.

Maureen L. Mulvihill has never watched the show, but she lives it every day. She is co-founder, president and CEO of Actuated Medical, Inc. (AMI), a Pennsylvania-based company that develops specialized medical devices. The devices include a system for unclogging feeding tubes, motors that assist MRI-related procedures and needles that gently draw blood.

AMI’s products rely on the same motion-control technologies that allow a quartz watch to keep time, a microphone to project sound and even a telescope to focus on a distant object in a sky. In general, the devices are portable, affordable and unobtrusive, making them appealing to doctors and patients.

Mulvihill, who’s trained in an area of engineering called materials science, says, “I’m really focused on how to translate technologies into ways that help people.” Continue reading “Meet Maureen L. Mulvihill”

A Bright New Method for Rapidly Screening Cancer Drugs

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Illustration of red, green and blue fluorescent proteins.
Chemists have devised a new approach to screening cancer drugs that uses gold nanoparticles with red, green and blue outputs provided by fluorescent proteins. Credit: University of Massachusetts Amherst.

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.

Continue reading “A Bright New Method for Rapidly Screening Cancer Drugs”