Meet Nels Elde and His Team’s Amazing, Expandable Viruses

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Nels Elde, Ph.D.
Credit: Kristan Jacobsen
Nels Elde, Ph.D.
Fields: Evolutionary genetics, virology, microbiology, cell biology
Works at: University of Utah, Salt Lake City
When not in the lab, he’s: Gardening, supervising pets, procuring firewood
Hobbies: Canoeing, skiing, participating in facial hair competitions

“I really look at my job as an adventure,” says Nels Elde. “The ability to follow your nose through different fields is what motivates me.”

Elde has used that approach to weave evolutionary genetics, bacteriology, virology, genomics and cell biology into his work. While a graduate student at the University of Chicago and postdoctoral researcher at the Fred Hutchinson Cancer Research Center in Seattle, he became interested in how interactions between pathogens (like viruses and bacteria) and their hosts (like humans) drive the evolution of both parties. He now works in Salt Lake City, where, as an avid outdoorsman, he draws inspiration from the wild landscape.

Outside the lab, Elde keeps diverse interests and colorful company. His best friend wrote a song about his choice of career as a cell biologist. (You can hear this song at the end of the 5-minute video Exit icon in which Elde explains his work.) Continue reading “Meet Nels Elde and His Team’s Amazing, Expandable Viruses”

Structural Studies Demystify Membrane Protein

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Animated structural model of TSPO.
Animated structural model of TSPO. Credit: Michigan State University.

Mitochondria have proteins that span their membranes to control the flow of messages and materials moving into and out of the organelle. One way scientists can learn more about how membrane proteins function—and how medicines might interact with them—is to determine their structures. But for a variety of reasons, obtaining the structures has been notoriously difficult.

Two structural studies have now shed light on the mysterious mitochondrial membrane protein TSPO. This protein plays a key role in transporting cholesterol and drugs into the cell’s mitochondria. While here, the cholesterol is converted to steroid hormones that are essential for numerous bodily functions. Although many researchers have been studying TSPO since the 1990s, they’ve remained uncertain about its mechanisms and how it truly functions. Continue reading “Structural Studies Demystify Membrane Protein”

Field Focus: Our Microbial Menagerie

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Trillions of microorganisms inhabit us—inside and out. Scientists are surveying these microbial metropolises to learn more about their role in health. Microbiologists Darren Sledjeski of NIGMS and Andrew Goodman Exit icon of Yale University share a few details of what researchers have learned so far.

Vitruvian man filled with bacteria.
Researchers are surveying the microbes that inhabit us to learn more about their role in health. Credit: Andrew Goodman, Yale University.
  1. The majority of the microbes that inhabit us are bacteria. The rest of the microbial menagerie is fungi and viruses, including ones that infect the bacteria! Collectively, our resident microorganisms are referred to as the human microbiota, and their genomes are called the human microbiome.
  2. Our bodies harbor more bacterial cells than human ones. Even so, the microbiota accounts for less than 3 percent of a person’s body mass. That’s because our cells are up to 10,000 times bigger in volume than bacterial cells.
  3. Your collection of bacteria has more genes than you do. Scientists estimate that the genomes of gut bacteria contain 100-fold or more genes than our own genomes. For this reason, the human microbiome is sometimes called our second genome.
  4. Most of our microbes are harmless, and some are helpful. For example, harmless microbes on the skin keep infectious microbes from occupying that space. Microbes in the colon break down lactose and other complex carbohydrates that our bodies can’t naturally digest.
  5. Different microbes occupy different parts of the body. Some skin bacteria prefer the oily nooks near the nose, while others like the dry terrain of the forearm. Bacteria don’t all fare well in the same environment and have adapted to live in certain niches. The NIGMS Findings Magazine article Body Bacteria: Exploring the Skin’s Microbial Metropolis shows what types of bacteria colonize where.
Screenshot from the iBiology video.
Are we more microbial than human? Richard Losick, a microbiologist at Harvard University, explores that question in this video lecture produced by iBiology Exit icon.
  1. Each person’s microbiota is unique. The demographics of microbiota differ among individuals. Diet is one reason. Also, while a type of microbe might be part of one person’s normal microbial flora, it might not be part of another’s, and could potentially make that person sick.
  2. Host-microbial interactions are universal. Microbial communities may vary from person to person, but everyone’s got them, including other creatures. For this reason, researchers can use model organisms to tease apart the complexities of host-microbial interactions and develop broad principles for understanding them. The mouse is the most widely used animal model for microbiome studies.
  3. The role of microbiota in our health isn’t entirely clear. While it’s now well accepted that the microbial communities that inhabit us are actively involved in a range of conditions—from asthma to obesity—research studies have not yet pinpointed why or how. In other words, the results may suggest that the presence of a bacterial community is associated with a disease, but they don’t show cause and effect.
  4. Most of our microbes have not been grown in the lab. Microbes require a certain mix of nutrients and other microbes to survive, making it challenging to replicate their natural environments in a petri dish. New culturing techniques are enabling scientists to study previously uncultivated microbes.
  5. The impact of probiotic and prebiotic products isn’t clear. Fundamental knowledge gaps remain regarding how these products may work and what effects they might have on host-microbial interactions. A new NIH effort to stimulate research in this area is under way.
  6. There’s even more we don’t know! Additional areas of research include studying the functions of microbial genes and the effects of gut microbes on medicines. The more we learn from these and other studies, the more we’ll understand how our normal microbiota interacts with us and how to apply that knowledge to promote our health.

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”

Cellular ‘Cruise Control’ Systems Let Cells Sense and Adapt to Changing Demands

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Cells are the ultimate smart material. They can sense the demands being placed on them during critical life processes and then respond by strengthening, remodeling or self-repairing, for instance. To do this, cells use “mechanosensory” systems similar to the cruise control that lets a car’s engine adjust its power output when going up or down hills.

Researchers are uncovering new details on cells’ molecular cruise control systems. By learning more about the inner workings of these systems, scientists hope ultimately to devise ways to tinker with them for therapeutic purposes.

Cell Fusion

To examine how cells fine-tune their architecture and force output during the merging or fusion of cells, Elizabeth Chen and Douglas Robinson of Johns Hopkins University teamed up with Daniel Fletcher of the University of California, Berkeley. Cell fusion is critical to many developmental and physiological processes, including fertilization, placenta formation, immune response, and skeletal muscle development and regeneration.

Illustration of cell fusion

Fingerlike protrusions of one cell (pink) invade another cell prior to cell fusion. Credit: Shuo Li. Used with permission from Developmental Cell.

Using the fruit fly Drosophila melanogaster as a model system, Chen’s research group Exit icon previously found that when two muscle cells merge during muscle development, fingerlike protrusions of one cell invade the territory of the other cell to promote fusion. In the new study, led by Chen, the researchers showed that cell fusion depends on the ability of the “receiving” cell to put up resistance against the invading cell Exit icon.

In fusing fruit fly cells, the scientists saw that in areas where the invading cells drilled in, the receiving cells quickly stiffened their cell skeletons, effectively pushing back. This mechanosensory response allows the outer membranes of the two cells to be pushed together and later fuse, Chen explains.

The team then explored the mechanisms underlying the stiffening response. They found that a protein called myosin II, which is part of the cell skeleton, senses the pushing force from the invading cell. Myosin II swarms to the fusion site and binds with fibers just beneath the cell membrane to put up the necessary resistance. Continue reading “Cellular ‘Cruise Control’ Systems Let Cells Sense and Adapt to Changing Demands”

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”

Surprising Role for Protein Involved in Cell Death

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C. elegans
Many of the key players in regulating apoptosis were discovered in C. elegans. This tiny roundworm has more than 19,000 genes, and a vast number of them are very similar to genes in other organisms, including people. Credit: Ewa M. Davison.

Our cells come equipped with a self-destruct mechanism that’s activated during apoptosis, a carefully controlled process by which the body rids itself of unneeded or potentially harmful cells. Scientists have long known that a protein called PSR-1 helps clean up the cellular remains. Now they’ve found that PSR-1 also can repair broken nerve fibers.

Ding Xue of the University of Colorado, Boulder, and others made the finding in the tiny roundworm C. elegans, which scientists have used to study apoptosis and identify many of the genes that regulate the process. While apoptotic cells sent “eat me” signals to PSR-1, injured nerve cells sent “save me” signals to the protein. These SOS signals helped reconnect the broken nerve fibers, called axons, that would otherwise degenerate after an injury.

Continue reading “Surprising Role for Protein Involved in Cell Death”

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”

5 Reasons Biologists Love Math

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Biologists use math in a variety of ways, from designing experiments to mapping complex biological systems. Credit: Stock image.

On Saturday (at 9:26:53 to be exact), math lovers and others around the world will celebrate Pi—that really long number that represents the ratio of the circumference of a circle to its diameter. I asked our scientific experts why math is important to biomedical research. Here are a few reasons.

  1. Math allows biologists to describe how molecules move in and out of cells, how bacteria shuttle through blood vessels, how drugs get broken down in the body and many other physiological processes.
  2. Studying the geometry, topology and other physical characteristics of DNA, proteins and cellular structures has shed light on their functions and on approaches for enhancing or disrupting those functions.
  3. Math helps scientists design their experiments, including clinical trials, so they result in meaningful data, a.k.a statistical significance.
  4. Scientists use math to piece together all the different parts of a cell, an organ or an entire organism to better understand how the parts interact and how perturbations in these complex systems may contribute to disease.
  5. Sometimes it’s impossible or too difficult to answer a research question through traditional lab experiments, so biologists rely on math to develop models that represent the system they’re studying, whether it’s a metastasizing cancer cell or an emerging infectious disease. These approaches allow scientists to indicate the likelihood of certain outcomes as well as refine the research questions.

Want more? Here’s a video with 10 reasons biologists should know some math.

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”