“Award Season” for Science

Science award
The biggest prizes each science “award season”: powerful glimpses into fundamental life processes that can yield deeper understanding of health and disease. Credit: Stock image.

Roll out the red carpet and shine up your shoes—it’s “award season” for science. The biggest prizes: powerful glimpses into fundamental life processes that can yield deeper understanding of health and disease.

For instance, the 2015 Albert Lasker Basic Medical Research Award Exit iconthat’s being presented today highlights the seminal work of two scientists on the DNA-damage response, a mechanism that protects the genomes of all living organisms. Chemicals, radiation and duplication errors during cell division are constantly harming our genetic material. Healthy cells respond with a complex network of proteins that work together to mend the damage and halt cell division until repairs are complete. If injury is beyond repair, the proteins trigger cell death. Errors in the DNA-damage response can lead to cancer, neurodegenerative disorders and immune deficiencies.

The scientists recognized today took important steps toward elucidating the mechanics of the DNA-damage response. Evelyn Witkin of Rutgers University established its existence and its basic features in bacteria. Continue reading

How Cells Manage Chance

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 second in an occasional series that explores these questions and explains how pursuing the answers could advance understanding of important biological processes.

Sample slide, variability of mRNA in yeast cells
The number of copies of mRNA molecules (bright green) observed here in yeast cells (dark blue) fluctuates randomly. Credit: David Ball, Virginia Tech.

For some health conditions, the cause is clear: A single altered gene is responsible. But for many others, the path to disease is more complex. Scientists are working to understand how factors like genetics, lifestyle and environmental exposures all contribute to disease. Another important, but less well-known, area of investigation is the role of chance at the molecular level.

One team working in this field is led by John Tyson Exit icon at Virginia Tech. The group focuses on how chance events affect the cell division cycle, in which a cell duplicates its contents and splits into two. This cycle is the basis for normal growth, reproduction and the replenishment of skin, blood and other cells throughout the body. Errors in the cycle are associated with a number of conditions, including birth defects and cancer. Continue reading

The Simple Rules Bacteria Follow to Survive

Left: Football stadium. Right: Colored contoured lines showing the periodic stops in the growth of a bacterial colony
Football image credit: Stock image. The colored contoured lines show the periodic stops in the growth of a bacterial colony. Credit: Süel Lab, UCSD.

What do these images of football fans and bacterial cells have in common? By following simple rules, each individual allows the group to accomplish tasks none of them could do alone—a stadium wave that ripples through the crowd or a cell colony that rebounds after antibiotic treatment.

These collective behaviors are just a few examples of what scientists call emergent phenomena. While the reasons for the emergence of such behavior in groups of birds, fish, ants and other creatures is well understood, they’ve been less clear in bacteria. Two independent research teams have now identified some of the rules bacterial cells follow to enable the colony to persist. Continue reading

Field Focus: Progress in RNA Interference Research

Scientists first noticed what would later prove to be RNA interference when puzzling over an unexpected loss of color in petunia petals. Subsequent studies in roundworms revealed that double-stranded RNA can inactivate specific genes. Credit: Alisa Z. Machalek.

In less than two decades, RNA interference (RNAi)—a natural process cells use to inactivate, or silence, specific genes—has progressed from a fundamental finding to a powerful research tool and a potential therapeutic approach. To check in on this fast-moving field, I spoke to geneticists Craig Mello Exit icon of the University of Massachusetts Medical School and Michael Bender of NIGMS. Mello shared the 2006 Nobel Prize in physiology or medicine with Andrew Fire Exit icon of Stanford University School of Medicine for the discovery of RNAi. Bender manages NIGMS grants in areas that include RNAi research.

How have researchers built on the initial discovery of RNAi?

A scientific floodgate opened after the 1998 discovery that it was possible to switch off specific genes by feeding microscopic worms called C. elegans double-stranded RNA that had the same sequence of genetic building blocks as a target gene. (Double-stranded RNA is a type of RNA molecule often found in, or produced by, viruses.) Scientists investigating gene function quickly began to test RNAi as a gene-silencing technique in other organisms and found that they could use it to manipulate gene activity in many different model systems. Additional studies led the way toward getting the technique to work in cells from mammals, which scientists first demonstrated in 2001. Soon, researchers were exploring the potential of RNAi to treat human disease. 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

Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs

Results of a data-mining study suggest a link between a common heartburn drug and heart attacks. Credit: Stock image.

Scouring through anonymized health records of millions of Americans, data-mining scientists found an association between a common heartburn drug and an elevated risk for heart attacks. Their preliminary results suggest that there may be a link between the two factors.

For 60 million Americans, heartburn is a painful and common occurrence caused by stomach acid rising through the esophagus. It’s treated by drugs such as proton-pump inhibitors (PPIs) that lower acid production in the stomach. Taken by about one in every 14 Americans, PPIs, which include Nexium and Prilosec, are the most popular class of heartburn drugs.

PPIs have long been thought to be completely safe for most users. But a preliminary laboratory study published in 2013 suggested that this may not be the case. The study, led by a team of researchers at Stanford University, showed that PPIs could affect biochemical reactions outside of their regular acid suppression action that would have harmful effects on the heart. Continue reading

Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy

Sarkis K. Mazmanian
Credit: New York Academy of Sciences
Sarkis K. Mazmanian, Ph.D.
Born in: The country of Lebanon, moved to Los Angeles when he was 1
Fields: Microbiology, immunology, neuroscience
Works at: California Institute of Technology
Awards won: Many, including the MacArthur Foundation “Genius” grant
Most proud of: The success of his trainees! “There’s nothing that comes close to the gratification and joy I feel when a student or research fellow goes on to be an independent scientist.”
When not in the lab or mentoring students, he’s: Spending time with his family, including his 1-year-old-son or going for an occasional run

As a child, Sarkis Mazmanian frequently took things apart to figure out how they worked. At the age of 12, he dismantled his family’s entire television set—to the dismay of his parents and the unsuccessful TV repairman.

“I wasn’t aware of this at the time, but maybe that was some sort of a foreshadowing that I would enjoy science,” Mazmanian says. “Scientists take biological systems apart to understand how they work.”

Mazmanian never thought he’d become a microbiologist, let alone a leading expert in the field. He began studying microbiology at the University of California, Los Angeles (UCLA), because it was the major that allowed him to do the most hands-on research. But as soon as he entered the field, he fell in love with the complexities of microbial organisms and the efficiency of their functions. Continue reading

Food for Thought: Nutrient-Detecting Brain Sensor in Flies

If you participated in a cupcake taste test, do you think you’d be able to distinguish a treat made with natural sugar from one made with artificial sweetener? Scientists have known for decades that animals can tell the difference, but what’s been less clear is how.

Fruit fly neurons in the brain (red) with nerve fibers (white) that extend to the gut.
For fruit flies, nutritive sugars activate a set of neurons in the brain (red) with nerve fibers (white) that extend to the gut. Credit: Jason Lai and Greg Suh, New York University School of Medicine.

Now, researchers at the New York University School of Medicine have identified a collection of specialized nerve cells in fruit flies that acts as a nutrient-detecting sensor, helping them select natural sugar over artificial sweetener to get the energy they need to survive.

“How specific sensory stimuli trigger specific behaviors is a big research question,” says NIGMS’ Mike Sesma. “Food preferences involve more than taste and hunger, and this study, which was done in an organism with many of the same cellular components as humans, gives us a glimpse of the complex interplay among the many factors.”

The study, described in the July 15 issue of Neuron, builds on the researchers’ earlier studies of feeding behavior that showed hungry fruit flies, even ones lacking the ability to taste, selected calorie-packed sugars over zero-calorie alternatives. The scientists, led by Greg Suh Exit icon and Monica Dus Exit icon, suspected that the flies had a molecular system for choosing energy-replenishing foods, especially during periods of starvation. Continue reading

From Basic Research to Bioelectronic Medicine

Kevin Tracey
Kevin J. Tracey of the Feinstein Institute for Medical Research, the research branch of the North Shore-LIJ Health System, helped launch a new discipline called bioelectronic medicine. Credit: North Shore-LIJ Studios.

By showing that our immune and nervous systems are connected, Kevin J. Tracey Exit icon of the North Shore-LIJ Health System’s Feinstein Institute for Medical Research helped launch a new discipline called bioelectronic medicine. In this field, scientists explore how to use electricity to stimulate the body to produce its own disease-fighting molecules.

I spoke with Tracey about his research, the scientific process and where bioelectronic medicine is headed next.

How did you uncover the connection between our immune and nervous systems?

My lab was testing whether a chemical we developed called CNI-1493 could stop immune cells from producing inflammation-inducing molecules called TNFs in the brain of rats during a stroke. It does. But we were surprised to find that this chemical also affects neurons, or brain cells. The neurons sense the chemical and respond by sending an electrical signal along the vagus nerve, which runs from the brain to the internal organs. The vagus nerve then releases molecules that tell immune cells throughout the body to make less TNF. I’ve named this neural circuit the inflammatory reflex. Today, scientists in bioelectronic medicine are exploring ways to use tiny electrical devices to stimulate this reflex to treat diseases ranging from rheumatoid arthritis to cancer. 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