The Inner Life of Nerve Cells

“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 Exit icon 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.

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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.

New Life for Toxic Antibiotics?

Pills and a bottle
Researchers found that the antibiotic trovafloxacin cuts off a channel for communication between cells and interferes with a cell-death process. Credit: iStockphoto.

Many compounds that show promise as new antibiotics for treating bacterial infections never make it to the clinic because they turn out to be toxic to humans as well as to bacteria. A research team led by Kodi Ravichandran Exit icon of the University of Virginia recently gained insights into why one such antibiotic, trovafloxacin, harms human cells. They found that the compound cuts off a channel for communication between cells, which in turn interferes with how dying cells are broken down and recycled by the body. Roughly 200 billion cells in the human body die and are replaced every day as part of a routine cleanup process, and interference in this process by trovafloxacin may have contributed to the serious liver damage seen in some patients in clinical trials of the drug. Understanding how trovafloxacin causes toxicity in people may help researchers re-engineer this and related compounds to make them safe and effective for use in fighting bacterial infections.

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Bleach vs. Bacteria

Screenshot of the video showing how chlorine affects a bacterial protein
Exposure to hypochlorous acid causes bacterial proteins to unfold and stick to one another, leading to cell death. Credit: Video segment courtesy of the American Chemistry Council. View video

Spring cleaning often involves chlorine bleach, which has been used as a disinfectant for hundreds of years. But our bodies have been using bleach’s active component, hypochlorous acid, to help clean house for millennia. As part of our natural response to infection, certain types of immune cells produce hypochlorous acid to help kill invading microbes, including bacteria.

Researchers funded by the National Institutes of Health have made strides in understanding exactly how bleach kills bacteria—and how bacteria’s own defenses can protect against the cellular stress caused by bleach. The insights gained may lead to the development of new drugs to breach these microbial defenses, helping our bodies fight disease.

Continue reading this new Inside Life Science article.

What Students Want to Know About Cells

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.

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Cool Image: Lighting up Brain Cells

Neurons activated with red or blue light.

Neurons activated with red or blue light using algae-derived opsins. Credit: Yasunobu Murata/McGovern Institute for Brain Research at MIT.

The nerve cells, or neurons, lit up in blue and red in this image of mouse brain tissue are expressing algae-derived, light-sensitive proteins called opsins. To control neurons with light, scientists engineer the cells to produce particular opsins, most of which respond to light in the blue-green range. Then they shine light on the cell to activate it. Now, a team of researchers led by Ed Boyden of the Massachusetts Institute of Technology and Gane Ka-Shu Wong of the University of Alberta has discovered an opsin that responds to red light preferentially, enabling them to manipulate two groups of neurons simultaneously with different colors of light and get a more comprehensive look at how those two sets of brain cells interact. Other opsins have shown potential for vision restoration in animal studies, and, because red light causes less damage to tissue than blue-green light, this new opsin might eventually be used for such treatments in humans.

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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

Learning More About Our Partners in Digestion

Bacteroides ovatus
Bacteroides ovatus. Credit: Eric Martens, University of Michigan Medical School.

After eating, we don’t do all the work of digestion on our own. Trillions of gut bacteria help us break food down into the simple building blocks our cells need to function. New research from an international team co-led by Eric Martens of the University of Michigan Medical School has uncovered how a strain of beneficial gut bacteria, Bacteroides ovatus, digests complex carbohydrates called xyloglucans that are found in fruits and vegetables. The researchers traced the microorganism’s digestive ability to a single piece of the genome. They also examined a publicly available set of genomic data, which included information from both humans and their resident bacteria, and found that more than 90 percent of 250 adults harbored at least one Bacteroides strain with xyloglucan-digesting capabilities. These results underscore the importance of the bacteria to human health and nutrition.

This work also was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

Learn more:
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Gut Reactions and Other Findings About Our Resident Microbes from Inside Life Science
Body Bacteria from Findings Magazine

Cool Image: Denying Microbial Moochers

V. cholerae and V. cholerae

Productive V. cholerae (yellow) and exploitive V. cholerae (red). Credit: Carey Nadell, Princeton University.

What looks like an abstract oil painting is actually an image of several cholera-causing V. cholerae bacterial communities. These communities, called biofilms, include productive and exploitive microbial members. The industrious bacteria (yellow) tend to thrive in denser biofilms (top) while moochers (red) thrive in weaker biofilms (bottom). In an effort to understand this phenomenon, Princeton University researchers led by Bonnie Bassler Exit icon discovered two ways the freeloaders are denied food. They found that some V. cholerae cover themselves with a thick coating to prevent nutritious carbon- and nitrogen-containing molecules from drifting over to the scroungers. In addition, the natural flow of fluids over biofilms can wash away any leftovers. Encouraging such bacterial fairness could boost the efficient breakdown of organic materials into useful products, such as biofuels. On the other hand, counteracting it could lead to better treatment of illnesses, like cholera, by starving the most productive bacteria and thereby weakening the infection.

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Visualizing Vessels

Blood vessels in a mouse retina
Blood vessels in a mouse retina visualized using cutting-edge imaging technology. Credit: Tom Deerinck and Mark Ellisman, NCMIR.

For poets and lovers, the eyes are the windows of the soul. For scientists and doctors, blood vessels at the back of the eye are windows into many diseases.

Blood vessel abnormalities can indicate a variety of serious conditions such as atherosclerosis (hardening of the arteries), heart attacks and strokes. But most vessels are buried beneath skin and other tissues, making them difficult to examine without surgery.

There’s one exception—in the eye. Unlike anywhere else in the body, larger vessels on the retina at the back of the eye are directly visible through the pupil, requiring essentially only light and magnifying lenses to view.

These vessels are used to diagnose glaucoma and diabetic eye disease. Because they display characteristic changes in people with high blood pressure, some researchers hope retinal vessels might one day help predict an impending stroke, congestive heart failure or other diseases stemming from dangerously high blood pressure.

The medical importance of retinal vessels piqued the interest of scientists funded by the National Institutes of Health at the National Center for Microscopy and Imaging Research (NCMIR) at the University of California, San Diego, who captured this micrograph image of mouse retinal vessels.

Continue reading this new Inside Life Science article