Researchers Receive $1.7M NIH Grant for Nematode Behavior Work

The National Institutes of Health has granted $1.7 million to Frank Schroeder, Associate Professor at the Boyce Thompson Institute, research associate Alexander Artyukhin and Professor Shawn Lockery of the University of Oregon in Eugene, to explore a fascinating social behavior in the roundworm C. elegans.

The microscopic nematode Caenorhabditis elegans exhibits complex social behaviors that represent important model systems for understanding sociality in animals. For example, C. elegans forage together, communicate information about food availability and environmental conditions, and change their behavior depending whether they’re alone or in a crowd. These simple organisms thus offer an opportunity to elucidate how animals use chemical signals to communicate.

C. elegans grow in the lab on media plates coated with bacteria. When developing larvae run out of food, they go out exploring for a few days before returning to hunker down and wait in tightly packed circles of worms, which under the microscope look like crawling bowls of spaghetti. These aggregated nematodes survive about twice as long as ones that are more spread out. Even when dispersed nematodes are exposed to extracts collected from densely-populated C. elegans cultures, they experience the same increase in lifespan. Artyukhin suspects that chemical cues are involved in both aggregation and improved survival.

Artyukhin began investigating this phenomenon as a postdoctoral researcher working with Leon Avery, then a professor at Virginia Commonwealth University in Richmond.

“When they consume all the bacteria, they become starved and a few days later they start to aggregate. Everybody sees that, but when I asked people why this happens, nobody could explain this to me,” said Artyukhin. “I started to look at this just out of curiosity.”

Artyukhin repeated his experiments on pure agar—a gelatin-like compound made from seaweed—instead of more complex culture media, and saw that the worms failed to aggregate. After systematically eliminating all the ingredients in the culture media, he discovered that C. elegans needs alcohol or acetate to aggregate—not enough to become intoxicated—just a small amount. Mutant worms that can’t metabolize alcohol will still aggregate when mixed with normal worms, but can’t put out the signal on their own.

Strangely, a very similar species in the same genus, C. briggsae, does not participate in this life-prolonging aggregation behavior.

“If you look at them under a microscope, you almost can’t distinguish them morphologically,” said Artyukhin. “Why do these species that not only look similar, but coexist in nature, behave so differently? That’s one of the questions we will try to answer,” said Artyukhin.

The team aims to collect and isolate components of the nematode extracts to identify the chemical that signals aggregation, but have yet to find that molecule. They suspect it is short-lived.

The group has already performed microarray experiments to identify genes that C. elegans turn on in response to alcohol. They plan to further explore these candidate genes by knocking them out individually and testing the worms’ ability to aggregate.

They also plan to feed the worms ethanol labeled with a carbon-13 isotope, so that they can track how the ethanol is metabolized and where that carbon travels in the body. The project also has a modeling component where they will see how the worms respond in different dimensions—such as in a sphere, or in a narrow line—and then model their behavior.

Understanding chemical communication in C. elegans may reveal important clues to communication in higher animals. Although it is unlikely that worms and humans function in exactly the same manner, knowledge of signaling mechanisms in simpler organisms has been proven to provide key insights in the biology of more complex animals.

Many of the biological pathways underlying the regulation of behavior are too complex to be easily studied in humans, but in nematodes, where the connections of every single neuron are known, scientists can more easily link behavior to physiology. And many of the same signaling molecules implicated in social behavior—such as dopamine and oxytocin—are well conserved throughout evolution, from nematodes to humans.

“Nematodes are a sweet spot between simple and complex,” said Artyukhin. “On one hand, they do exhibit in a variety of behaviors, where they signal to each other. On the other hand, they’re simple enough that there is a real possibility to be able to track this behavior to individual neurons, genes and molecules.”