Catherine Rankin admires her favourite research subject -- a one-millimetre worm - photo by Martin Dee

UBC Reports | Vol. 52 | No. 1 | Jan. 9, 2006

Simple Worm Holds Clues to Human Learning, Memory

By Lorraine Chan

What can we learn from a brainless, one-millimetre worm about human behaviour and mental disorders? Plenty, as UBC Psychology Prof. Catharine Rankin is showing through her work with the C. elegans nematode.

For the past 15 years, Rankin, a behaviour, memory and learning expert, has been focusing on this simple worm to better grasp the complex workings of humans. Her research may uncover genetic tools that could be used for treating disorders like schizophrenia, a diagnosis given to almost half the patients hospitalized for mental disorders.

For Rankin, the worm -- a self-fertilizing hermaphrodite with a life span of two weeks -- makes a perfect research subject. She explains that while humans have a trillion neurons and rats have millions to billions, the nematode has only 302.

“If you want to understand basic properties of electricity, would you start with a computer or a flashlight?” asks Rankin. “The worm is my flashlight.”

She says in addition to its simplicity, the worm holds a lot of other attractions for researchers. In 1998, C. elegans was the first animal to have its genome sequenced. As well, there are 2,000 worm experts in the world who pool their findings in a shared database.

“It’s like working on an animal with an instruction manual,” says Rankin, who focuses on deciphering the genes and cellular processes that govern memory and learning.

“I study habituation, which is the simplest form of learning.”

Habituation, she explains, refers to how a healthy person learns to filter out background stimuli such as the feeling of cloth on the body, the sound of one’s own breathing or the traffic noises from a nearby street.

“Schizophrenics habituate abnormally,” says Rankin. “They have a hard time filtering out irrelevant stimuli.”

Rankin aims to isolate the genes that play a role in habituation for worms. “We can then understand the rules and apply those principles for genes in other animals including humans.”

In 1990, Rankin was the first researcher to prove that C. elegans could change its behaviour with memory and experience. By tapping the side of the petri dish, Rankin cued the nematode to move backwards. She found that worms would learn to ignore the taps if they were repeated a number of times. As well, Rankin discovered that worms could remember this training for at least 48 hours.

She was also first among her peers to discover some of the worm’s mechanisms of memory. She tested a number of genes until she found one that affected memory, and then measured how much of it was being made after the tapping exercise. Worms that had learned showed they had more of that particular gene.

Rankin is also looking at mechanisms that control how memories are stored, retrieved or erased. Such mechanisms may eventually be used to help people release traumatic memories such as rape, she says.

Pulitzer-prize winning science writer Matt Ridley, author of Nature via Nurture, Genes Experience and What Makes us Human, recently dubbed Rankin a “brilliant young scientist in Vancouver who has essentially observed in real time the changes in the nematode as it learns new experience.”

To achieve this, Rankin uses specific genes that have had green fluorescent protein attached. The protein lights up and can be used to measure how much of that gene is being produced and used. Rankin has shown that if a worm gets lots of stimulation during development there are high levels of genes that make synapses, which are the connections between nerve cells. If the developing worm is deprived of stimulation, there are fewer of these genes, suggesting weaker synapses.

“No one has shown how experience causes gene expression changes in living animals at the cellular level before,” she says. “Down the road, this information may give us tools for gene therapy when it comes to treating memory disorders or reversing the effects of early deprivation.”

An example Rankin gives for deprivation would be severely neglected children who have not been stimulated, held or nurtured early in life.

Rankin has also contributed to a growing body of research that shows that genes don’t operate as immutable blueprints, but change with experience and when interacting with surroundings. Again, she observes these subtle shifts through watching how the worm’s green fluorescent protein gets brighter when genes are turned up and dimmer when the genes are turned down.

“Prior to that, we saw genes as a software program that always runs the same, but that’s not the case at all,” she explains. “Instead, think of each gene as having one or more volume knobs. And these can, within a certain range, be turned up or down by its experience.”

Rankin’s research has garnered funding from the Natural Sciences and Engineering Research Council, Canadian Institutes of Health Research and the Human Early Learning Partnership.