Elegant science from the lowly roundworm

Ignore the ick factor, for a moment, and consider the lowly roundworm.

Also known by its more formal name, Caenorhabditis elegans, the 1 millimeter-long nematode has helped scientists all over the world uncover new insights about biology and genetics since the 1960s.

In fact, it was 1963 when biologist Sydney Brenner, then doing research in England, turned to the worm in his study of the development of the nervous system. Brenner shared the 2002 Nobel Prize in Physiology or Medicine with H. Robert Horvitz and John E. Sulston for their discoveries concerning genetic regulation of organ development and programmed cell death. In his Nobel lecture, Brenner paid homage to C. elegans and told the story of its journey from “joke organism” to a powerful, living experimental system. “Without a doubt,” he said, “the fourth winner of the Nobel Prize this year is Caenorhabditis elegans; it deserves all of the honor but, of course, it will not be able to share the monetary award.”

In part, that’s because his tiny “colleagues” in the lab didn’t live long enough to cash the check. But that short lifespan – C. elegans lives about two weeks – makes the organism an ideal choice for scientists studying developmental biology, genetics, neurobiology, and aging. The worms are easy to grow in bulk – each worm produces about 300 progeny during a life cycle. In 1998, the worm’s complete genome was sequenced – a first for a multicellular organism.

Broad Associate Members Fred Ausubel, Gary Ruvkun, and Fatih Yanik are continually probing a variety of biological questions that require using whole animals rather than isolated cells. C. elegans, which can live in a glass dish, feasting on bacteria, can be handled in large numbers by robotic arms in the lab. Scientists then use robotic microscopes, computers, and computational techniques known as algorithms to scan digital pictures of the little worms and identify those that responded appropriately to experimental conditions. Anne Carpenter and her colleagues in the Imaging Platform at the Broad are creating these algorithms, which can identify C. elegans that are resistant to obesity or infection by pathogens., which could someday lead to drugs for these conditions.

Simple as it is, the worm has wriggled into the limelight again. As recently as last week, in fact, researchers at Princeton University suggested that C. elegans may provide insights into human fertility.

A hallmark of aging in women, of course, is menopause, the loss of fertility that happens between age 45 and 55, on average. As women age, their egg cells decline in quality, and the risk of infertility, birth defects, and miscarriage increase. But little is known about what mechanisms regulate the quality of human egg cells.

Writing in Cell, Coleen T. Murphy, a molecular biologist and Princeton, and colleagues found that “C. elegans and humans share many aspects of reproductive aging.” As the nematode’s short-lived biological clock ticks, its oocytes, or unfertilized eggs, begin to break down. Researchers associate this decline with increased secretion of a protein called TGF-ß, or transforming growth factor beta. The same protein is found in humans, although its interactions are more complex and the protein performs many different functions.

Although much work needs to be done – the protein may not play the same role in women – C. elegans research may ultimately open the door to new knowledge about how to extend female fertility.

“Both human and C. elegans females reproduce about one-third to one-half of their lives, and thus undergo significant reproductive aging on proportional time scales,” the authors write, “implying that genetic mechanisms may link reproduction to longevity in both...”