Dr Yee Lian Chew doesn’t mind standing out in a crowd, nor does she object to being known as the “worm lady”.
“When I say I work on worm brains, it’s a good conversation starter.”
Dr Chew is a Senior Research Fellow in Neuroscience at Flinders University’s College of Medicine and Public Health, and the worm in question is the roundworm C. elegans.
It is a far cry from your common or garden earthworm, however, being just a millimetre in length and transparent, each animal carrying exactly 300 neurons, or brain cells.
But these diminutive creatures are 80% genetically identical to humans and could hold the key to how our own brains work, including how to better manage chronic pain without the use of potentially problematic drugs.
“I’m interested in the changes in the brain when you learn and remember something,” says Dr Chew. “We think that for long-term memory there’s a particular change, and for short-term memory there’s another type of change.
“This is encoded in a particular part of the brain, and then upon remembering those brain cells become active again and chemical changes happen.”
But what does all this have to do with worms?
“These worms can do a lot with a small number of brain cells. They crawl around. They eat. They mate. They say, ‘Hi,’ to each other. They have interesting social behaviours. They move towards certain chemicals, avoid others,” says Dr Chew.
“We know a lot about what they do, but we still don't really know how they learn and change their behaviours depending on experience, or how that memory is encoded in their 300 neurons.”
These are all questions that scientists ask about bigger brains, but in the case of the worm, the process takes place in a dramatically more compact system which is easier to follow.
The worms’ transparency is also an advantage when it comes to microscopy because you can see the neurons in action in an intact animal, labelled with fluorescent proteins to distinguish the 10% or so that are chemical sensing neurons.
“But the other amazing thing that we can do with a transparent animal is functionally turn on or off certain neurons by shining a light on them.”
Since 2015, a large part of Dr Chew’s work has been to investigate pain-sensing circuits and how they become more excitable.
While at the MRC Laboratory of Molecular Biology in Cambridge, she picked up work that had been started by a former colleague from Japan. “He had left but had kept incredible records. So I looked through all of his work and basically continued on from that.
“We found one neurochemical signal was released by the neurons that sense touch, and those chemicals were essential for the sensitisation or the increased excitation of the pain circuit.
“If you take the signal away, the pain circuit still senses pain but it doesn't become sensitised and doesn't become more excitable with repeated stimulation.”
While the neurochemical was invertebrate-specific, the research led Dr Chew to approach the treatment of chronic pain from a different angle.
Instead of management strategies to block pain, Dr Chew began to look at ways to stop pain becoming chronic by targeting the sensitisation of pain cells. She is using the worm system to identify how that might work, and investigating other neurochemicals which might play a role. She acknowledges that this work will have to move on to more complex animals at some time.
“Absolutely. I will probably go to either flies or mice first. There are several established pain models of those and to see if those particular neurochemicals, first, affect pain sensing, and second, affect pain sensitisation in those animals.
“Perhaps we can try to develop ways with pharmacologists to block those signals in people and see what happens.”
But for now she is happy to be the odd worm woman out.
“When you come into a team and work on something a little unusual, you have to think slightly differently to how everyone else thinks.
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