Tag: Cells

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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 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”

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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”

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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”
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Correcting a Cellular Routing Error Could Treat Rare Kidney Disease

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AGT protein and peroxisomes in untreated and treated cells.
The altered AGT protein (red) and peroxisomes (green) appear in different places in untreated cells (top), but they appear together (shown in yellow) in cells treated with DECA (bottom). Credit: Carla Koehler/Reproduced with permission from Proceedings of the National Academy of Sciences USA. View larger image.

Our cells have organized systems to route newly created proteins to the places where they’re needed to do their jobs. For some people born with a rare and potentially fatal genetic kidney disorder called PH1, a genetically altered form of a particular protein mistakenly ends up in mitochondria instead of in another organelle, the peroxisome. This cellular routing error of the AGT protein results in the harmful buildup of oxalate, which leads to kidney failure and other problems at an early age.

In new work led by UCLA biochemist Carla Koehler Exit icon, researchers used a robotic screening system to identify a compound that interferes with the delivery of proteins to mitochondria. Koehler’s team Exit icon showed that adding a small amount of the compound, known as DECA, to cells grown in the laboratory prevented the altered form of the AGT protein from going to the mitochondria and sent it to the peroxisome. The compound also reduced oxalate levels in a cell model of PH1.

The team’s findings suggest that DECA, which is already approved by the Food and Drug Administration for treating certain bacterial infections, could be a promising candidate for treating children affected by PH1. And, Koehler notes, the screening strategy that she and her team used to identify DECA as a potential therapy may help researchers identify other new therapies for the disorder.

This work was funded in part by NIH under grant R01GM061721.

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Molecules Known to Damage Cells May Also Have Healing Power

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Free radicals in an ying-yang symbol
Biology in balance: Molecules called free radicals—like the peroxide molecules illustrated here—have a reputation for being dangerous. Now, they’ve revealed healing powers. In worms, at least. Credit: Stock image

When our health is concerned, some molecules are widely labeled “good,” while others are considered “bad.” Often, the truth is more complicated.

Consider free radical molecules. These highly reactive, oxygen-containing molecules are well known for damaging DNA, proteins and other molecules in our bodies. They are suspected of contributing to premature aging and cancer. But now, new research shows they might also have healing powers.

Using the oft-studied laboratory roundworm known as C. elegans, a research group led by Andrew Chisholm at the University of California, San Diego, made a surprising discovery. Free radicals, specifically those made in cell structures called mitochondria, appear necessary for skin wounds to heal. In fact, higher (but not dangerously high) levels of the molecules can actually speed wound closure.

If further research shows the same holds true in humans, the work could point to new ways to treat hard-to-heal wounds, like diabetic foot ulcers.

This work was funded in part by NIH under grants R01GM054657 and P40OD010440.

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Cells by the Numbers

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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.

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Mighty Mitochondria

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Mitochondria from the heart muscle cell of a rat.
Mitochondria (red) from the heart muscle cell of a rat. Nearly all our cells have these structures. Credit: Thomas Deerinck, National Center for Microscopy and Imaging Research Exit icon.

Meet mitochondria: cellular compartments, or organelles, that are best known as the powerhouses that convert energy from the food we eat into energy that runs a range of biological processes.

As you can see in this close-up of mitochondria from a rat’s heart muscle cell, the organelles have an inner membrane that folds in many places (and that appears here as striations). This folding vastly increases the surface area for energy production. Nearly all our cells have mitochondria, but cells with higher energy demands have more. For instance, a skin cell has just a few hundred, while the cell pictured here has about 5,000.

Scientists are discovering there’s more to mitochondria than meets the eye, especially when it comes to understanding and treating disease.

Read more about mitochondria in this Inside Life Science article.

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Cool Image: Outsourcing Cellular Housekeeping

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Mouse optic nerve and retina. Credit: Keunyoung Kim, Thomas Deerinck and Mark Ellisman, National Center for Microscopy and Imaging Research, UC San Diego.
This image shows the mouse optic nerve and retina. Credit: Keunyoung Kim, Thomas Deerinck and Mark Ellisman, National Center for Microscopy and Imaging Research Exit icon, UC San Diego.

In this image, the optic nerve (left) leaves the back of the retina (right). Where the retina meets the optic nerve, visual information begins its journey from the eye to the brain. Taking a closer look, axons (purple), which carry electrical and chemical messages, meet astrocytes (yellow), a type of brain cell. Recent research has found a new and surprising role for these astrocytes.

Biologists have long thought that all cells, including neurons, degrade and reuse pieces of their own mitochondria, the little powerhouses that provide energy to cells. Using cutting-edge imaging technology, researchers led by Mark Ellisman of the University of California, San Diego, and Nicholas Marsh-Armstrong of Johns Hopkins University have caught neurons in the mouse optic nerve in the act of passing some of their worn out mitochondria to neighboring astrocytes, which then did the dirty work of recycling.

The researchers also showed that neurons in other regions of the brain appear to outsource mitochondrial breakdown to astrocytes as well. They suggest that it will be important to confirm that this process occurs in other parts of the brain and to determine how possible defects in the outsourcing may contribute to or underlie neuronal dysfunction or neurodegenerative diseases.

This work also was funded by NIH’s National Eye Institute and National Institute on Drug Abuse.

Learn more:
University of California, San Diego News Release and Blog Posting
How Cells Take Out the Trash Article from Inside Life Science

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The Inner Life of Nerve Cells

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“Before this research, we didn’t even know that neurons had this special mechanism to control neuropeptide function. This is why we do basic research. This is why it’s important to understand how neurons work, down to the subcellular and molecular levels.”—Kenneth Miller”

Nerve cells (neurons) in the brain use small molecules called neuropeptides to converse with each other. Disruption of this communication can lead to problems with learning, memory and other brain functions. Through genetic studies in a model organism, the tiny worm C. elegans, a team led by Kenneth Miller of the Oklahoma Medical Research Foundation has uncovered a previously unknown mechanism that nerve cells use to package, move and release neuropeptides. The researchers found that a protein called CaM kinase II, which plays many roles in the brain, helps control this mechanism. Neuropeptides in worms lacking CaM kinase II spilled out from their packages before they reached their proper destinations. A more thorough understanding of how neurons work, provided by studies like this, may help researchers better target drugs to treat memory disorders and other neurological problems in humans.

This work also was funded by NIH’s National Institute of Mental Health.

Learn more:
Oklahoma Medical Research Foundation News Release Exit icon

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What Students Want to Know About Cells

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Cell Day 2014

During a live online chat dubbed “Cell Day,” scientists at NIGMS recently fielded questions about the cell and careers in research from middle and high school students across the country. Here’s a sampling of the questions and answers, some of which have been edited for clarity or length.

What color are cells?
While cells with lots of iron, like red blood cells, may be red, usually cells are colorless.

How many different types of cells can be found inside the human body?
There are about 200 cell types and a few trillion total cells in the human body. That does not include bacteria, fungi and mites that live on the body.

Is it possible to have too many or not enough cells?
The answer depends on cell type. For example, within the immune system, there are many examples of diseases that are caused by too many or not enough cells. When too many immune cells accumulate, patients get very large spleens and lymph nodes. When too few immune cells develop, patients have difficulty fighting infections.

How fast does it take for a cell to produce two daughter cells?
Some cells, for example bacterial ones, can produce daughter cells very fast when nutrients are available. The doubling time for E. coli bacteria is 20 minutes. Other cells in the human body take hours or days or even years to divide.

Do skin cells stretch or multiply when you gain weight?
The size of cells is tightly regulated and maintained so they do not stretch much. As the surface area of the body increases with weight gain, the number of skin cells increases.

Why do cells self-destruct?
The term for cellular self-destruction is “apoptosis” or “programmed cell death.” Apoptosis is very important for normal development of humans and other animals as it ensures that we do not have too many cells and that “unhealthy” cells can be eliminated without causing harm to the surrounding cells. For instance, did you know that human embryos have webbing between their fingers and toes (just like ducks!)? Apoptosis eliminates the cells that form the web so that you are born with toes and fingers.

In what field is there a need for new scientists?
I would say that there is a need for scientists who can work at the interface between the biological and biomedical sciences and the data sciences. Knowing sophisticated mathematics and having computer skills to address questions like ‘what does this biomedical data tell us about particular diseases’ is still a challenge.

What is a scientist’s daily work day like? Is all of your time spent in a lab testing or like in an office throwing ideas around?
There are lots of different kinds of jobs a scientist can have. Many work in labs where they get to do experiments AND throw ideas around. Working in a lab is a lot of fun—you learn things about the world that no one has known before (how cool is that?). Other important jobs that scientists can do include writing about science as a journalist, helping other scientists patent new technologies they invent as a patent agent or lawyer, or working on important scientific policy issues for the government or other organizations.