Category: Tools and Techniques

Viral Views: New Insights on Infection Strategies

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The following images show a few ways in which cutting-edge research tools are giving us clearer views of viruses—and possible ways to disarm them. The examples, which highlight work involving HIV and the coronavirus, were funded in part by our Biomedical Technology Research Resources program.

Uncloaking HIV’s Camouflage

HIV capsid with (right, red) and without (left) a camouflaging human protein.
HIV capsid with (right, red) and without (left) a camouflaging human protein. Credit: Juan R. Perilla, Klaus Schulten and the Theoretical and Computational Biophysics Group, University of Illinois at Urbana-Champaign.

To sneak past our immune defenses and infect human cells, HIV uses a time-honored strategy—disguise. The virus’ genome is enclosed in a protein shell called a capsid (on left) that’s easily recognized and destroyed by the human immune system. To evade this fate, the chrysalis-shaped capsid cloaks itself with a human protein known as cyclophilin A (in red, on right). Camouflaged as human, the virus gains safe passage into and through a human cell to deposit its genetic material in the nucleus and start taking control of cellular machinery.

Biomedical and technical experts teamed up to generate these HIV models at near-atomic resolution. First, structural biologists at the Pittsburgh Center for HIV Protein Interactions Exit icon used a technique called cryo-electron microscopy (cryo-EM) to get information on the shape of an HIV capsid as well as the capsid-forming proteins’ connections to each other and to cyclophilin A. Then experts at the Resource for Macromolecular Modeling and Bioinformatics Exit icon fed the cryo-EM data into their visualization and simulation programs to computationally model the physical interactions among every single atom of the capsid and the cyclophilin A protein. The work revealed a previously unknown site where cyclophilin A binds to the capsid, offering new insights on the biology of HIV infection. Continue reading “Viral Views: New Insights on Infection Strategies”

Ticks, Mice and Microbes—Studying Disease Spread

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Maria Diuk-Wasser
Credit: Oscar Gonzalez (Diuk-Wasser’s husband)
Maria Diuk-Wasser
Hometown: Buenos Aires, Argentina
Childhood dream job: Veterinarian
Hobbies: Hiking and gardening with her son (age 10) and daughter (age 7)
Favorite music: Salsa
Worksite: Lab at Columbia University and forests in coastal New England

Maria Diuk-Wasser grew up on the 10th floor of an apartment building in the middle of a bustling city. With no forests or meadows nearby, she read book after book about the natural world and surrounded herself with houseplants.

“I yearned for nature,” Diuk-Wasser says. “But my parents couldn’t provide it. They’re city people. They didn’t know anything about hiking or camping.”

These days, Diuk-Wasser still spends a lot of time in a city—she’s a professor at Columbia University in New York, the most populous city in the U.S.—but she also gets plenty of time in the woods. She hikes for hours through coastal New England forests, some of the loveliest in the country, searching for what many consider less-than-lovely inhabitants: mice and ticks. Continue reading “Ticks, Mice and Microbes—Studying Disease Spread”

El Niño Season Temperatures Linked to Dengue Epidemics

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Screen shot from the video showing dengue incidence in Southeast Asia.
Incidence of dengue fever across Southeast Asia, 1993-2010. Note increasing incidence (red) starting about June 1997, which corresponds to a period of higher temperatures driven by a strong El Niño season. At the end of the El Niño event, in January 1999, dengue incidence is much lower (green). Credit: Wilbert van Panhuis, University of Pittsburgh.

Weather forecasters are already warning about an intense El Niño season that’s expected to alter precipitation levels and temperatures worldwide. El Niño seasons, characterized by warmer Pacific Ocean water along the equator, may impact the spread of some infectious diseases transmitted by mosquitoes.

In a study published last month in the Proceedings of the National Academy of Sciences, researchers reported a link between intense dengue fever epidemics in Southeast Asia and the high temperatures that a previous El Niño weather event brought to that region.

Dengue fever, a viral infection transmitted by the Aedes mosquito, can cause life-threatening high fever, severe joint pain and bleeding. Infection rates soar every two to five years. Interested in understanding why, an international team of researchers collected and analyzed incidence reports including 3.5 million dengue fever cases across eight Southeast Asian countries spanning an 18-year period. The study is part of Project Tycho, an effort to study disease transmission dynamics by mining historical data and making that data freely available to others. Continue reading “El Niño Season Temperatures Linked to Dengue Epidemics”

Cool Image: DNA Origami

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Computer-generated sketch of a DNA origami folded into a flower-and-bird structure.

A computer-generated sketch of a DNA origami folded into a flower-and-bird structure. Credit: Hao Yan, Arizona State University.

This image of flowers visited by a bird is made of DNA, the molecule that provides the genetic instructions for making living organisms. It shows the latest capability of a technique called DNA origami to precisely twist and fold DNA into complex arrangements, which might find future use in biomedical applications. Continue reading “Cool Image: DNA Origami”

How Cells Manage Chance

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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 “How Cells Manage Chance”

The Simple Rules Bacteria Follow to Survive

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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 “The Simple Rules Bacteria Follow to Survive”

Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs

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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 “Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs”

Digging Deeply Into Data for the Causes of Disease

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Hunting for the cause of a disease can be like tracing a river back to its many sources. Myriad factors, large and small, may contribute to a condition. One approach to the search focuses on the massive amounts of genomic and other biological data that scientists are gathering in the course of their studies. To examine this data and look for meaningful patterns and other clues, scientists turn to bioinformatics, a field focused on the development of analytical methods and software tools.

Here are a few examples of how National Institutes of Health-funded scientists are using bioinformatics to dig deeply into data and learn more about the development of diseases, including Huntington’s, preeclampsia and asthma.

Huntington’s Disease

Network of proteins that interact with huntingtin

Researchers have mapped a network of 2,141 proteins that all interact either directly or through one other protein with huntingtin (red), the protein associated with Huntington’s disease. Credit: Cendrine Tourette, Buck Institute for Research on Aging, J Biol Chem 2014 Mar 7;289(10):6709-26 Exit icon.

The cause of Huntington’s disease, a degenerative neurological disorder with no known cure, may appear simple. It begins with a change in a single gene that alters the shape and functioning of the huntingtin protein. But this protein, whether in its normal or altered form, does not act alone. It interacts with other proteins, which in turn interact with others.

A research team led by Robert Hughes of the Buck Institute for Research on Aging set out to understand how this ripple effect contributes to the breakdown in normal cellular function associated with Huntington’s disease. The scientists used experimental and computational approaches to map a network of 2,141 proteins that interact with the huntingtin protein either directly or through one other protein. They found that many of these proteins were involved in cell movement and intercellular communication. Understanding how the huntingtin protein leads to mistakes in these cellular processes could help scientists pursue new approaches to developing treatments. Continue reading “Digging Deeply Into Data for the Causes of Disease”

Meet Karen Carlson

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Karen Carlson
Credit: Karen Carlson
Karen Carlson
Fields: Systems biology, bacterial biofilms
Born and raised in: Alaska
Undergraduate student at: The University of Alaska, Anchorage
When not in the lab, she’s: Out and about with her 3-year-old son, friends and family
Secret talent: “I make some really good cookies.”

Karen Carlson got a surprise in her 10th grade biology class. Not only did she find out that she enjoyed science (thanks to an inspiring teacher), but, as she puts it, “I realized that I was really good at it.”

In particular, she says, “I was good at putting all the pieces [of a scientific question] together. And that’s what I had the most fun with—looking at systems: how things fit together and the flow between them.”

These are perfect interests for a budding systems biologist, which is what Carlson is on her way to becoming. She’s a senior in college on track to graduate this year with a bachelor’s degree in biology from the University of Alaska, Anchorage (UAA). Next, she plans to enroll in a master’s degree program at UAA, and eventually to pursue a Ph.D. in a biomedical field. Continue reading “Meet Karen Carlson”

Simulating the Potential Spread of Measles

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Try out FRED Measles:

  1. Go to http://fred.publichealth.
    pitt.edu/measles
    Exit icon
  2. Select “Get Started”
  3. Pick a state and city
  4. Play both simulations

To help the public better understand how measles can spread, a team of infectious disease computer modelers at the University of Pittsburgh has launched a free, mobile-friendly tool that lets users simulate measles outbreaks in cities across the country.

The tool is part of the Pitt team’s Framework for Reconstructing Epidemiological Dynamics, or FRED, that it previously developed to simulate flu epidemics. FRED is based on anonymized U.S. census data that captures demographic and geographic distributions of different communities. It also incorporates details about the simulated disease, such as how contagious it is.

Screenshot of the FRED simulation.

A free, mobile-friendly tool lets users simulate potential measles outbreaks in cities across the country. Credit: University of Pittsburgh Graduate School of Public Health.

Continue reading “Simulating the Potential Spread of Measles”