Tag: Cellular Processes

How a Cell Knows Friend From Foe

1 comment

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 first in an occasional series that will explore these questions and explain how pursuing the answers could advance understanding of important biological processes.

Video screen shot showing different strains of amoeba cells in red and green.
This video shows different strains of amoeba cells in red and green. As cells move toward one another, they use two sets of proteins to recognize others from the same strain. When close relatives meet, their proteins match and the cells join together to form a multicellular structure. When cells from different strains meet, their proteins don’t match, so they can’t aggregate. Credit: Shigenori Hirose, Baylor College of Medicine.

Cells are faced with many decisions: When’s the best time to produce a new protein? To grow and split into two? To treat another cell as an invader? Scientists are working to understand how cells make these and many other decisions, and how these decisions contribute to health and disease.

An active area of research on cell decisions focuses on allorecognition, the ability of an organism to distinguish its own cells from those of another. Immune cells use a system called the major histocompatibility complex (MHC) to identify which cells belong to the body and which are foreign. The particular set of MHC proteins on the outer surface of a cell helps immune cells decide whether it does not belong and should be attacked.

But the system isn’t perfect. Invading pathogens can go undetected, and the body can mistake its own cells for intruders. Continue reading “How a Cell Knows Friend From Foe”

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

0 comments

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”

Surprising Role for Protein Involved in Cell Death

0 comments
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 “Surprising Role for Protein Involved in Cell Death”

Scientists Shine Light on What Triggers REM Sleep

1 comment
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 “Scientists Shine Light on What Triggers REM Sleep”

Zinc’s Role in Healthy Fertilization

0 comments
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 “Zinc’s Role in Healthy Fertilization”

Cells by the Numbers

0 comments

Cells are the basic unit of life—and the focus of much scientific study and classroom learning. Here are just a few of their fascinating facets.

3.8 billion

Nerve Cells
Developing nerve cells, with the nuclei shown in yellow. Credit: Torsten Wittmann, University of California, San Francisco.

That’s how many years ago scientists believe the first known cells originated on Earth. These were prokaryotes, single-celled organisms that do not have a nucleus or other internal structures called organelles. Bacteria are prokaryotes, while human cells are eukaryotes.

0.001 to 0.003

This is the diameter in centimeters of most animal cells, making them invisible to the naked eye. There are some exceptions, such as nerve cells that can stretch from our hips to our toes, sending electrical signals throughout the body.

1665

Red blood Cells
Oxygen-transporting red blood cells. Credit: Dennis Kunkel, Dennis Kunkel Microscopy, Inc.

In that year, British scientist Robert Hooke coined the term cell to describe the porous, grid-like structure he saw when viewing a thin slice of cork under a microscope. Today, scientists study cells using a variety of high-tech imaging equipment as well as rainbow-colored dyes and a green fluorescent protein derived from jellyfish.

200

That’s how many different types of cells are in the human body, including those in our skin, muscles, nerves, intestines, blood and bones.

3 to 5

Believe it or not, that’s the approximate number of pounds of bacteria you’re carrying around, depending on your size. Even though bacterial cells greatly outnumber ours, they’re much smaller than our cells and therefore account for less than 3 percent of our body mass. Scientists are learning more about how our body bacteria contribute to our health.

24

Snapshot of a phase of the cell cycle.
A snapshot of a phase of the cell cycle. Credit: Jean Cook and Ted Salmon, UNC School of Medicine.

This is the typical length in hours of the animal cell cycle, the time from a cell’s formation to when it splits in two to make more cells.

120

That’s the approximate lifespan in days of a human red blood cell. Other cell types have different lifespans, from a few weeks for some skin cells to as long as the life of the organism for healthy neurons.

50 to 70 billion

Each day, approximately this many cells die in the human body as part of a normal process that serves a healthy and protective role. Those that die in the largest numbers are skin cells, blood cells and some cells that line structures like organs and glands.

Get stats on what scientists have learned so far about genetics.

Learn more:

Inside the Cell Booklet
Studying Cells Fact Sheet

Modifying Bacterial Behavior

0 comments
Biofilm
Communication through quorum sensing is key to the formation of biofilms, slimy bacterial communities that can cause infections and are often stubbornly resistant to antibiotics. Credit: P. Singh and E. Peter Greenberg.

Like a person trailing the aroma of perfume or cologne, bacteria emit chemical signals that let other bacteria of the same species know they’re there. Bacteria use this chemical communication system, called quorum sensing, to assess their own population size. When they sense a large enough group, or quorum, the microbes modify their behavior accordingly. Many disease-causing bacteria use quorum sensing to launch a coordinated attack when they’ve amassed in sufficient numbers to overwhelm the host’s immune response.

Chemist Helen Blackwell of the University of Wisconsin-Madison has been making artificial compounds that mimic natural quorum-sensing signals, as well as some that block a natural signal from binding to its protein target—a step needed to produce a change in bacterial behavior. By altering key building blocks in these protein targets one by one, Blackwell’s team found that small changes could convert an activation signal into an inhibitory signal, or vice versa, indicating that small-molecule control of quorum sensing is very finely tuned.

Improved understanding of the molecular basis of quorum sensing could help scientists design more potent compounds to disrupt these signals. Using such compounds to quiet quorum sensing may provide a new way to control disease-causing bacteria that reduces the chances an infection will become resistant to treatment.

This work was funded in part by NIH under grants R01GM109403 and T32GM008505.

Learn more:
University of Wisconsin-Madison News Release Exit icon
Blackwell Lab Exit icon

Steering Cells Down the Right Path

1 comment
In these time-lapse videos of 60 images taken over an hour, cell receptors move around the cell surface in search of the missing signal that will tell the cell where to go (top video). Once the receptors locate the signal (bottom video), they stay put in the region of the cell membrane that is closest to the signal. Credit: David Sherwood, Duke University.

Even traveling cells need help with directions. In fact, it’s crucial. For processes such as wound healing and organ development to take place, cells must be able to efficiently move throughout organisms. Receptor proteins on a cell’s surface rely on navigational signals from molecules called netrins to point them in the right direction.

The receptors don’t just sit around waiting for a signal. Studying the simple worm C. elegans, David Sherwood Exit icon and his research team at Duke University discovered that in the absence of netrin, the receptors rapidly cluster and reassemble in different areas of the cell’s membrane. When the receptors finally detect a netrin signal, they stabilize and correctly orient the cell. The finding might point to new ways to interfere with cells’ built-in navigation systems to hamper cell migration in metastatic cancer or encourage the regrowth of damaged cells in neurodegenerative diseases such as Parkinson’s.

This research was funded in part by NIH under grants R01GM100083 and P40OD010440.

Learn more:
Duke University News Release Exit icon

Cool Image: Training Cells to Devour Dying Neighbors

2 comments
A healthy cell that has ingested dying cells.

A healthy cell (green) that has ingested dying cells (purple). Credit: Toru Komatsu, University of Tokyo.

In this image, a healthy cell (green) has engulfed a number of dying cells (purple) just as a predator might ingest wounded or dying prey. A team of researchers is hoping to use this same strategy at the cellular level to help treat infection, neurodegenerative diseases or cancer.

Our bodies routinely use a process called phagocytosis to rid themselves of unhealthy cells. Takanari Inoue Exit icon at Johns Hopkins University and collaborators at the University of Tokyo set out to investigate the molecular underpinnings of phagocytosis. Their goal was to endow laboratory-grown human cells with phagocytotic skills, namely the ability to recognize, swallow and digest dying cells. The scientists tried to do this by inserting into the cells two molecules known to play a role in phagocytosis.

The engineered cells accomplished the first two tasks—they recognized and surrounded dying cells. But they didn’t digest what they’d engulfed. Now the researchers are looking for a molecular trigger to get the engineered cells to complete this last task.

Eventually, the scientific team aims to build artificial cells that are programmed to target and destroy abnormal cells, such as those ravaged by bacteria, cancer or other diseases.

Learn more:
Johns Hopkins News Release Exit icon
How Cells Take Out the Trash Article from Inside Life Science
Cellular Suicide: An Essential Part of Life Article from Inside Life Science

Meet Janet Iwasa

1 comment
Janet Iwasa
Credit: Janet Iwasa
Janet Iwasa
Fields: Cell biology and molecular animation
Works at: University of Utah
Raised in: Indiana and Maryland
Studied at: University of California, San Francisco, and Harvard Medical School
When not in the lab she’s: Keeping up with her two preschool-aged sons
Something she’s proud of that she’ll never try again: Baking a multi-tiered wedding cake, complete with sugar flowers, for a friend’s wedding.

Janet Iwasa wouldn’t have described herself as an artistic child. She didn’t carry around a sketch pad, pencils or paintbrushes. But she remembers accompanying her father, a scientist at the National Institutes of Health, to his lab on the weekends. She’d spend hours doodling in a drawing program on his old Macintosh computer while he worked on experiments.

“I always remember wanting to be a scientist, and that’s probably highly inspired by my dad,” says Iwasa. Her early affinity for art and technology set her on an unusual career path to become a molecular animator. A typical work day now finds her adapting computer programs originally designed to bring characters like Buzz Lightyear to life to help researchers probe complicated, dynamic interactions within cells.

Iwasa’s interest in animation was sparked when she was a graduate student in cell biology, studying a protein called actin, which helps cells to move and change shape. At the time, the only visual representations she had of actin networks were flat, two-dimensional drawings on paper. When she saw an animation of the dynamic movement of a molecule called kinesin, she thought, “Why are we relying on oversimplified, static illustrations [of molecules], when we can be doing something like this video?”

Within a year, she was taking an animation class at a local college. She quickly realized that she would need more intensive instruction to be able to animate complex biological processes. A few summers later, she flew to Hollywood for a 3-month training program in industry-standard animation technology.

The oldest student in that course—and the only woman—Iwasa immediately began thinking about how to adapt a standard animator’s toolkit to illustrate the inner life of cells. A technique used to create the effect of human hair blowing in the wind could also show the movement of an RNA molecule. A chunk of computer code used to make the facets of a soccer ball fall apart and come back together in a different order could be adapted to model virus assembly and disassembly.

Her Findings

Following her training, Iwasa spent 2 years as a National Science Foundation Discovery Corps fellow, producing the Exploring Life’s Origins Exit icon exhibit with the Boston Museum of Science and the Szostak Lab at Massachusetts General Hospital/Harvard Medical School. As part of the multi-media exhibit, she created animations to illustrate how the simplest living organisms may have evolved on early Earth.

Since then, Iwasa has helped researchers model such complex actions as how cells ingest materials, how proteins are transported across a cell membrane, and how the motor protein dynein helps cells divide.

Screenshot from the video that shows how a protein called clathrin forms a cage-like container that cells use to engulf and ingest materials
Iwasa developed this video to show how a protein called clathrin forms a cage-like container that cells use to engulf and ingest materials.

Iwasa calls her animations “visual hypotheses”: The end results may be beautiful, but the process of animation itself is what encapsulates, clarifies and communicates the science.

“It’s really building the animated model that brings insights,” she says. “When you’re creating an animation, you’re really grappling with a lot of issues that don’t necessarily come up by any other means. In some cases, it might raise more questions, and make people go back and do some more experiments when they realize there might be something missing” in their theory of how a molecular process works.

Now she’s working with an NIH-funded research team at the University of Utah to develop a detailed animation of how HIV enters and exits human immune cells.

Abbreviated CHEETAH Exit icon, the full name of the group is the Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV.

“In the HIV life cycle, there are a number of events that aren’t really well understood, and people have different ideas of how things happen,” says Iwasa. She plans to animate the stages of viral infection in ways that reflect different proposals for how the process works, to give researchers a new way to visualize, communicate—and potentially harmonize—their hypotheses.

The full set of Iwasa’s HIV-related animations will be available online as they are completed, at http://scienceofhiv.org Exit icon, with the first set launching in the fall of 2014.

Learn more:
Janet Iwasa’s TED Talk: How animations can help scientists test a hypothesis Exit icon
Janet Iwasa’s 3D model of an HIV particle was a winner in the 2014 BioArt contest Exit icon sponsored by Federation of American Societies for Experimental Biology
NIH Director’s blog post about Iwasa and her HIV video animation