Skip Navigation
The Elegant Worm

Keith Weller

The Elegant Worm

They’re cheaper than mice, simpler than fruit flies, transparent and hermaphroditic. In fact, these microscopic worms, known as Caenorhabditis elegans, are the multicellular organisms of choice for several scientists making breakthrough discoveries in neurodegeneration and immune response.

Only 1 millimeter in length, the worm is also transparent, which makes it easy for scientists to observe what happens inside its cells. In addition, with such a short life span—about two or three weeks—the nematode is ideal for longitudinal studies, especially those that examine cell aging and cell death. “For studies with mice, you have to wait a year to [see the effect on their lifespan],” says Jiou Wang, assistant professor in Biochemistry and Molecular Biology (BMB). “That’s not efficient.”

In his lab, Wang uses C. elegans to research the neurodegeneration that occurs in amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease. Neurodegeneration, the hallmark of diseases such as Alzheimer’s, Parkinson’s and Huntington’s, involves the death or damage of neurons. What results are symptoms including dementia and the loss of memory, speech and movement.

A subset of ALS is believed to be caused by mutations in the gene SOD1, which is what Wang studies in C. elegans. Having built a strain of the worm that contains a mutated human SOD1 gene, he examines the mechanisms of how its protein misfolds and how that misfolding is associated with toxicity among motor neurons.

Many human neural functions are conserved in the worm—but where humans have billions of neurons, C. elegans has exactly 302. “The wiring of its neurons is well-known,” says Wang, MD, PhD. “It has a uniquely simple neurosystem.” But he is quick to point out that the organism has all the classes of neurons that humans do, such as sensory neurons, motor neurons and interneurons (also called connector neurons).

Immune response is another area of research made more efficient by the worm. Researchers Valeria Culotta, a BMB professor, and Julie Gleason, a postdoctoral fellow in Culotta’s lab, are using C. elegans to explore the role of manganese in the growth of pathogens within a host organism. Pathogens such as Salmonella and Staphylococcus—both bacteria—need manganese to be infectious. The researchers are testing what happens to fungal pathogens when the supply of manganese is altered. Specifically, they are looking at the fungus Candida albicans, which causes thrush. Most commonly afflicting infants, thrush is a yeast infection that healthy humans fight so effectively they fail to notice its presence—but it can cause a deadly systemic infection for those who are immunocompromised.

It turns out that C. elegans has evolved with a simple form of innate immunity (compared to humans, who have both innate and acquired immunity). This immunity shares some common features with that of humans, and the worm is vulnerable to the same types of infections. “With mice it would take months,” says Gleason, PhD. “We infect the worms, monitor for four days, and we get a large amount of data.” Because C. elegans has only 959 cells, monitoring pathogenesis in the organism is especially easy. With the help of the humble worm, Culotta and Gleason are gathering new insights into how the infection progresses when the host is overloaded or depleted of the metal—which could lead to new treatment for those afflicted.

The Caenorhabditis Genetics Center in Minnesota stocks every strain available. For $7 a shipment, scientists like Culotta, Gleason and Wang can mail-order any strain, with a wide selection of mutations. A shipment of C. elegans arrives on Petri dishes containing their favorite food, E. coli, and the worms are ready to be used. “They’re infinitely cheaper than mice,” says Culotta.

Worm strains can be homegrown, too. Culotta calls Gleason a “great builder of worms. She can make you any kind of worm you want.”

Because they’re hermaphrodites, says Gleason, tinkering with their genetics is easy: “You mate your gene of interest into your worm once, and then they’ll do everything for you. It’s simpler than the fruit fly.”

And models don’t get much heartier than C. elegans. “You can freeze them away like a roast beef,” says Culotta. “You can thaw them out 10 or 15 years later, and they’re ready to go.”

According to Thomas Hartung, director of the Center for Alternatives to Animal Testing (CAAT), there has been a fivefold increase in publications that use the worm in biomedical and environmental toxicology studies in the last decade, and the organism easily lends itself to high-throughput applications. If researchers can identify the pathways of human toxicity that are conserved in the worm, he says, they will be able to test more chemicals, while dramatically reducing the costs associated with animal testing. In fact, CAAT has promoted C. elegans research and considers such applications in their funding program, says Hartung, who holds the Doerenkamp-Zbinden Professor and Endowed Chair for Evidence-Based Toxicology.

Clearly, C. elegans’ rise in the laboratory benefits more mammals than just humans. Hartung, MD, PhD, believes it is clearly outperforming mouse, hamster, rabbit and guinea pig models for large-scale toxicity screening. “This microscopic worm,” he says, “can become a most valuable work horse.”

A SHORT WORM...
At 1mm in length, C. elegans is one of the smallest organisms with a nervous system. About half of known human disease genes have a homologue in this nematode. The worm’s genome was fully sequenced in 1998.
THAT SHARES...
C. elegans uses the same neurotransmitters as vertebrates, and the pharmacology of this round worm’s receptors is strikingly similar to that of humans.
EATS A LOT AND…
Blind and deaf, C. elegans can smell and taste and detect heat. Most of its life is spent eating. A healthy C. elegans defecates about every 45 seconds throughout its lifespan.
HAS SEX OFTEN.
Though C. elegans lives only two weeks, it leads a busy life. it has sex early and often, usually with itself. In the wild, it is free living (as opposed to parasitic), lives in soil and eats bacteria and fungi.
Source: In The Beginning Was The Worm, Andrew Brown.

Comments

This forum is closed

Read about our policy on comments to magazine articles.

design element
Online Extras

A Worm Unlocks a Mystery

A Worm Unlocks a Mystery

Biochemist Valeria Culotta explains how the humble worm C. elegans is making research discoveries possible.

Listen Now

Talk to Us

Amazed? Enthralled? Disappointed? We want to hear from you. Share your thoughts on articles and your ideas for new stories:

Download the PDF

Get a copy of all News Briefs articles in PDF format. Read stories offline, optimized for printing.

Download Now (2.7MB)

Talk to Us

Amazed? Enthralled? Disappointed? We want to hear from you. Share your thoughts on articles and your ideas for new stories: