Field Focus: Making Chemistry Greener

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

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

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

Digging Deeply Into Data for the Causes of Disease

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

Surprising Role for Protein Involved in Cell Death

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 Exit icon 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

Meet Karen Carlson

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

5 Reasons Biologists Love Math

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

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 Exit icon, Matthew Wilson Exit icon and Emery Brown Exit icon 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

Simulating the Potential Spread of Measles

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

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

Zinc’s Role in Healthy Fertilization

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. View video Exit icon

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 Exit icon, plus other researchers at Northwestern University, evaluated the role that zinc plays in healthy fertilization Exit icon. 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