August 3, 2009
While an undergraduate majoring in dance at Tulane University, Christina Paulson broke her ankle. Sidelined from her dance classes for a semester, she took biology courses and discovered a new love.
“I think everything about biology is interesting. You can see it in everything around us. I’m just curious about what’s going on one step smaller than we can see,” Paulson says.
At Southern Methodist University, she is focusing on worms, in particular a tiny nematode called C. elegans. The worm is one of the most useful creatures in the laboratory for a number of reasons, including the length of its life cycle – three days.
Paulson and her adviser, Assistant Professor of Biological Sciences Jim Waddle, thought that the worm might be useful for laboratory toxicity screening. “You normally apply chemicals to individual cells or mice. We wanted to use worms because they’re a nice compromise. They tell us much more than cells, but are much cheaper and have a faster developmental process than mice.”
Worms, however, are filter feeders, which creates problems when testing drugs, Paulson says. They live in the dirt eating and excreting everything, too quickly for toxins to have any effect. So Paulson doused the nematodes with mutagenic chemicals. Then she examined them and thousands more, looking for worms with abnormal intestines. Finally she found a worm that had outpouchings all along the intestine. Paulson and Waddle excitedly tested the mutant worm strain and found that it did, indeed, show sensitivity to toxins. This strain of mutant worms some day may be used by pharmaceutical companies to test new, better drugs to treat cancer or heart disease.
Paulson presented the results of their research to the International C. elegans Meeting at UCLA in 2007.
In the meantime, Paulson has continued to examine more worms that have been chemically treated and has discovered three more with mutant intestines. “They have mutations in different genes, but all have weird intestines,” she says. “The hope is that we can figure out how these different genes relate to one another and figure out how this affects drug sensitivity.”
Paulson, an SMU graduate student in biology, talked about the impact of Darwin's Theory of Evolution on her life and her research as part of SMU's celebration of Charles Darwin's 200th birthday on Feb. 12, 2009. Her remarks, a video, and a photo of the worm she mentions, follow:
When I was asked to talk about how Charles Darwin has influenced my life or my research, I immediately remembered my first introduction to the scientist.
When I was in fifth grade I listened as my biology teacher told us about a day when Darwin was peeling bark from a tree and come across two species of beetles, he enclosed one in each hand, eager to study them. Then he saw another type of beetle and was so intent on collecting it as well, that he used his mouth as a third storage container. Unfortunately for Darwin, the beetle in his mouth was a rare bombardier beetle that squirted a noxious fluid into his throat. The squirting beetle was spat out and the other two beetles were dropped from the shock.
As a ten-year-old, the message I took home from this story was not to put beetles in my mouth, and while I still think that is a valuable lesson, the more prominent message is the desperate passion and curiosity that Darwin felt for science.
Unarguably, one of Darwin's most famous contributions to science is his theory of evolution. The theory of evolution is the notion that all life is related and descended from a common ancestor; from oranges to orangutans, everything is related.
Skeptics of Darwin's theory of evolution joke that if Darwin was right, we’ll find out in a few millions years. Well, the majority of biology labs have decided not to wait quite that long and currently do research based on the concept that all living organisms are related, hence studying one animal could elucidate information about another. Scientific research of human bodies is often unreasonable, so scientists use stand-ins called model-organisms, such as worms, flies, and mice. While on outward physical appearance alone, flies and humans don’t look at all similar, on the inside, where DNA and genes provide instructions for the processes essential to life, the two are very akin. Because we know that humans are closely related to other organisms, we can study these model organisms to learn about humans.
In the lab I work in, we use a small worm to explore ways to treat illnesses and diseases in humans. It's hard to imagine that the worms crawling on this plate bear much of a resemblance to us, but in fact homologues have been identified for 60-80% of human genes. While they are small, these worms are sophisticated multi-cellular animals with many different organs and tissues including muscle, skin, intestines, glands, reproductive systems, and nervous systems. My research focuses on using the worm as a system for studying drugs. Part of my work is optimizing a system by which worms are used for preliminary drug screens. Potential drugs can be tested on a population of worms to see if they have the desired effect before testing the medication on humans. We also use the worm to look at the way that drugs are processed once they are ingested. By finding mutations that cause drug sensitivity in the worm, we hope to be able to discover ways to help humans who are over-sensitive to medication.
The advantages of using model organisms to study human conditions seem infinite. Firstly is the ethical advantage of being able to glean information about humans without locking them in a lab and subjecting them to unusual concoctions, injections, and dissections. To rattle off just a few of the other advantages of studying a model organism; they render rapid results with their short life cycles, they are relatively inexpensive to maintain, and are smaller and more simple to manipulate than humans.
As a testament to how useful model organisms really are, these worms have been used to make significant advances in diabetes, obesity, cancer, Alzheimer’s disease, Parkinson’s disease and many more human conditions. So, our lab will continue to take advantage of the relationship between worms and humans as we work to improve the way that human drugs are developed, and in the meantime, I’ll take another lesson from Darwin and try to keep the worms out of my mouth.
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