Unprecedented Views of HIV

Visualizations can give scientists unprecedented views of complex biological processes. Here’s a look at two new ones that shed light on how HIV enters host cells.

Animation of HIV’s Entry Into Host Cells

Screen shot of the video
This video animation of HIV’s entry into a human immune cell is the first one released in Janet Iwasa’s current project to visualize the virus’ life cycle. As they’re completed, the animations will be posted at http://scienceofhiv.org Exit icon.

We previously introduced you to Janet Iwasa, a molecular animator who’s visualized complex biological processes such as cells ingesting materials and proteins being transported across a cell membrane. She has now released several animations from her current project of visualizing HIV’s life cycle Exit icon. The one featured here shows the virus’ entry into a human immune cell.

“Janet’s animations add great value by helping us consider how complex interactions between viruses and their host cells actually occur in time and space,” says Wes Sundquist, who directs the Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV Exit icon at the University of Utah. “By showing us how different steps in viral replication must be linked together, the animations suggest hypotheses that hadn’t yet occurred to us.” Continue reading “Unprecedented Views of HIV”

Illuminating Biology

This time of year, lights brighten our homes and add sparkle to our holidays. Year-round, scientists funded by the National Institutes of Health use light to illuminate important biological processes, from the inner workings of cells to the complex activity of the brain. Here’s a look at just a few of the ways new light-based tools have deepened our understanding of living systems and set the stage for future medical advances.

RSV infected cell
A new fluorescent probe shows viral RNA (red) in an RSV-infected cell. Credit: Eric Alonas and Philip Santangelo, Georgia Institute of Technology and Emory University.

Visualizing Viral Activity

What looks like a colorful pattern produced as light enters a kaleidoscope is an image of a cell infected with respiratory syncytial virus (RSV) lit up by a new fluorescent probe called MTRIPS (multiply labeled tetravalent RNA imaging probes).

Although relatively harmless in most children, RSV can lead to bronchitis and pneumonia in others. Philip Santangelo of the Georgia Institute of Technology and Emory University, along with colleagues nationwide, used MTRIPS to gain a closer look at the life cycle of this virus.

Once introduced into RSV-infected cells, MTRIPS latched onto the genetic material of individual viral particles (in the image, red), making them glow. This enabled the researchers to follow the entry, assembly and replication of RSV inside the living cells. Continue reading “Illuminating Biology”

Forecasting Infectious Disease Spread with Web Data

Just as you might turn to Twitter or Facebook for a pulse on what’s happening around you, researchers involved in an infectious disease computational modeling project are turning to anonymized social media and other publicly available Web data to improve their ability to forecast emerging outbreaks and develop tools that can help health officials as they respond.

Mining Wikipedia Data

Screen shot of the Wikipedia site
Incorporating real-time, anonymized data from Wikipedia and other novel sources of information is aiding efforts to forecast and respond to emerging outbreaks. Credit: Stock image.

“When it comes to infectious disease forecasting, getting ahead of the curve is problematic because data from official public health sources is retrospective,” says Irene Eckstrand of the National Institutes of Health, which funds the project, called Models of Infectious Disease Agent Study (MIDAS). “Incorporating real-time, anonymized data from social media and other Web sources into disease modeling tools may be helpful, but it also presents challenges.”

To help evaluate the Web’s potential for improving infectious disease forecasting efforts, MIDAS researcher Sara Del Valle of Los Alamos National Laboratory conducted proof-of-concept experiments involving data that Wikipedia releases hourly to any interested party. Del Valle’s research group built models based on the page view histories of disease-related Wikipedia pages in seven languages. The scientists tested the new models against their other models, which rely on official health data reported from countries using those languages. By comparing the outcomes of the different modeling approaches, the Los Alamos team concluded that the Wikipedia-based modeling results for flu and dengue fever performed better than those for other diseases. Continue reading “Forecasting Infectious Disease Spread with Web Data”

Field Focus: Bringing Biology Into Sharper View with New Microscopy Techniques

Composite image of mitochondria in a cell
In this composite image of mitochondria in a cell, the left panel shows a conventional optical microscopy image, the middle panel shows a three-dimensional (3-D) STORM image with color indicating depth, and the right panel shows a cross-section of the 3-D STORM image. Credit: Xiaowei Zhuang laboratory, Howard Hughes Medical Institute, Harvard University. View larger image.

Much as a photographer brings distant objects into focus with a telephoto lens, scientists can now see previously indistinct cellular components as small as a few billionths of a meter (nanometers). By overcoming some of the limitations of conventional optical microscopy, a set of techniques known as super-resolution fluorescence microscopy has changed once-blurry images of the nanoworld into well-resolved portraits of cellular architecture, with details never seen before in biology. Reflecting its importance, super-resolution microscopy was recognized with the 2014 Nobel Prize in chemistry.

Using the new techniques, scientists can observe processes in living cells across space and time and study the movements, interactions and roles of individual molecules. For instance, they can identify and track the proteins that allow a virus to invade a cell or those that enable tumor cells to migrate to distant parts of the body in metastatic cancer. The ability to analyze individual molecules, rather than collections of molecules, allows scientists to answer longstanding questions about cellular mechanisms and behavior, such as how cells move along a surface or how certain proteins interact with DNA to regulate gene activity. Continue reading “Field Focus: Bringing Biology Into Sharper View with New Microscopy Techniques”

Outwitting Antibiotic Resistance

Marine scene with fish and corals
The ocean is a rich source of microbes that could yield infection-fighting natural molecules. Credit: National Oceanic and Atmospheric Administration Exit icon.

Antibiotics save countless lives and are among the most commonly prescribed drugs. But the bacteria and other microbes they’re designed to eradicate can evolve ways to evade the drugs. This antibiotic resistance, which is on the rise due to an array of factors, can make certain infections difficult—and sometimes impossible—to treat.

Read the Inside Life Science article to learn how scientists are working to combat antibiotic resistance, from efforts to discover potential new antibiotics to studies seeking more effective ways of using existing ones.

 

Field Focus: Precision Gene Editing with CRISPR

Bacterial cells infected by viruses.
Bacterial cells can be infected by viruses (shown in red and purple) and have evolved ways to defend themselves. Credit: Stock image.

Like humans, bacteria can be infected by viruses and have evolved ways to defend themselves. Researchers are now adapting this bacterial “immune system” to precisely and efficiently edit genes in cells from humans and a wide range of other organisms. Scientists are excited about the tremendous potential of this powerful tool for advancing biomedical research and treating diseases.

The bacterial defense system is called CRISPR, for clustered regularly interspaced short palindromic repeats. A breakthrough in understanding CRISPR came from examining bacteria used by the dairy industry for the production of yogurt and cheese. In a study published in 2007, researchers showed that these bacteria insert viral DNA sequences into their own genomes and use that information to disarm the virus when it attacks again. Subsequent research has shown that the CRISPR system consists of small RNA molecules that target specific viral DNA sequences and proteins that cut the DNA, thus destroying the virus.

Researchers have already adapted CRISPR into a gene-editing tool that’s quicker, cheaper and more precise than existing methods. Researchers can use CRISPR to add, delete, rev up or tone down certain genes as well as create animal models for studying human diseases. The ability to precisely target genes in human cells is expected to speed progress in the development of gene-based therapies.

Although much is known about CRISPR, we still have a lot to learn. For example, how do bacterial cells obtain and insert the viral DNA into their genome? What triggers production of the CRISPR RNA molecules? How are invading viral DNAs targeted for destruction? This last question is answered in part by a pair of findings described in an earlier post, A Crisper View of the CRISPR Gene-Editing Mechanism. We also want to figure out how we can make the CRISPR gene-editing tool even more versatile and precise.

The CRISPR story offers a good example of how studying basic biological processes leads to new—and sometimes unexpected—insights and applications.

Emily Carlson also contributed to this blog post.

Related advances:
CRISPR/Cas9 Protein Complex Can Be Programmed to Recognize and Cleave RNA Exit icon
CRISPR System Adapted to Reversibly Regulate Gene Expression Exit icon

Improving the Odds of Surviving Sepsis

Acupuncture
A form of acupuncture—or a drug that mimics its effect—may one day lead to an anti-inflammatory therapy for people with sepsis. Credit: Stock image.

A leading cause of death in U.S. intensive care units is sepsis, an overwhelming immune response to infection that triggers body-wide inflammation and can cause organ failure.

Sepsis is challenging to diagnose and treat. Many of its early signs, such as fever and difficulty breathing, are similar to those of other conditions. When doctors do not detect sepsis until a more advanced stage, they are often unable to stop its progression or prevent its complications.

“Sepsis is a complex problem,” says Sarah Dunsmore of the National Institutes of Health (NIH). “We need more research at all levels—from the molecular to the patient—to improve sepsis diagnosis and treatment and to enhance the quality of life for sepsis survivors.”

NIH-funded scientists use a variety of tools, including blood tests and acupuncture, in their quest to detect sepsis early, treat it quickly and reduce its later effects.

Read more about sepsis research in this Inside Life Science article.

On the Trail of Drug-Defying Superbugs

Antibiotic-resistant strains of Staphlyococcus aureus bacteria (purple) have become the most common cause of skin infections seen in hospital emergency departments. Credit: NIH’s National Institute of Allergy and Infectious Diseases.
Antibiotic-resistant strains of Staphlyococcus aureus bacteria (purple) have become the most common cause of skin infections seen in hospital emergency departments. Credit: NIH’s National Institute of Allergy and Infectious Diseases.

In the United States alone, at least 2 million people each year develop serious infections with bacteria that have become resistant to the antibiotics we use to combat them, and about 23,000 die, according to the Centers for Disease Control and Prevention. Antibiotic resistance can turn once-manageable infections into “superbug” diseases that are difficult—and sometimes impossible—to treat.

Scientists funded by the National Institutes of Health are studying many aspects of antibiotic resistance, including how it spreads. Read this Inside Life Science article for just a few research examples and how the work could aid efforts to curb the emergence of resistance.

How Cells Take Out the Trash

Proteins entering the proteasome. Credit: Office of Biological and Environmental Research of the U.S. Department of Energy Office of Science.
When proteins enter the proteasome, they’re chopped into bits for re-use. Credit: Office of Biological and Environmental Research of the U.S. Department of Energy Office of Science.

As people around the world mark Earth Day (April 22) with activities that protect the planet, our cells are busy safeguarding their own environment.

To keep themselves neat, tidy and above all healthy, cells rely on a variety of recycling and trash removal systems. If it weren’t for these systems, cells could look like microscopic junkyards—and worse, they might not function properly. Scientists funded by the National Institutes of Health are therefore working to understand the cell’s janitorial services to find ways to combat malfunctions.

Read more about how cells take out the trash and handle recycling in this Inside Life Science article.

Capitalizing on Cellular Conversations

Fat cells
Fat cells such as these listen for incoming signals like FGF21, which tells them to burn more fat. Credit: David Gregory and Debbie Marshall. All rights reserved by Wellcome Images.

Living things are chatty creatures. Even when they’re not making actual sounds, organisms constantly communicate using chemical signals that course through their systems. In multicellular organisms like people, brain cells might call, “I’m in trouble!” signaling others to help mount a protective response. Single-celled organisms like bacteria may broadcast, “We have to stick together to survive!” so they can coordinate certain activities that they can’t carry out solo. In addition to sending out signals, cells have to receive information. To help them do this, they use molecular “ears” called receptors on their surfaces. When a chemical messenger attaches to a receptor, it tells the cell what’s going on and causes a response.

Scientists are following the dialogue, learning how cell signals affect health and disease. They’re also starting to take part in the cellular conversations, inserting their own comments with the goal of developing therapies that set a diseased system right.

Continue reading this new Inside Life Science article