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Trying to solve the mystery of fetal DNA

by Luanne Williams

Research that could pave the way to solving a medical mystery in sheep will also help a Wingate University senior on the path to becoming a physician.  

A female college student wearing blue gloves dissects a piece of tissue from a sheep.

Even before enrolling at Wingate University, Hannah Teague knew that as a biology major with hopes of becoming a doctor she’d need some research experience on her medical-school application. What she didn’t expect is an opportunity that would take her to Idaho twice this year to rub shoulders with lead scientists from the United States Department of Agriculture.

“So much of what they would be talking about I had heard of from my science courses, but it was on such a deeper level than I was used to studying, kind of over my head,” says Teague, a Monroe resident and Piedmont High School graduate headed into her senior year at Wingate. “I’d have to say, ‘I’m sorry, can you clarify? I’m not sure I really understand what that means.’”

But Alison Brown, her biology professor and mentor for the project, says Teague’s 4.0 GPA, her strong work ethic and growing understanding of courses such as Reproductive Physiology make her a perfect fit for the research. Her curiosity doesn’t hurt either.

“What’s great about Hannah, she always asks questions,” Brown says.

A flock of sheep stand in front of mountains in Idaho.

Thanks to a Reeves Summer Research Grant, the two are in the midst of tackling a big question about sheep and a medical phenomenon called fetal microchimerism. When foreign DNA exists within an organism, it forms what is known as a chimera. Fetal microchimerism occurs when a small amount of DNA from a fetus crosses over the placenta into the mother’s circulatory system. It happens naturally in humans, but the presence of fetal DNA after pregnancy has been linked to inflammatory responses involved in certain autoimmune diseases in women. Also, some studies have shown that the fetal DNA, which is often eliminated after pregnancy, could have a positive effect on wound healing. And still other research has found no effect at all from the presence of fetal DNA in a woman’s body after pregnancy.

Needless to say, many questions remain unanswered. And when it comes to sheep, which have a different type of placenta from humans, the mystery is even greater.

“The ability of fetal DNA to cross the placenta into maternal blood or tissues has not been thoroughly examined in sheep, especially in common breeds used within the United States sheep industry,” Brown explained in her research proposal. She wants to determine, first, if male fetal cells are able to cross into the mother’s circulation and remain after pregnancy. And if so, does this exchange differ depending on the number of lambs a ewe has given birth to over her lifetime?

“Whatever the outcome of this basic study, we will gain a greater understanding of normal physiological function that occurs during pregnancy in these animals,” Brown says.

‘Discovery’ project

If fetal DNA is found, the research may open the door to more questions: Does microchimerism contribute to the health of the mother in a positive or negative way? Or does fetal DNA lie dormant in a cell?

Brown, who has collaborated with USDA scientists at the U.S. Sheep Experiment Station (USSES) on undergraduate research projects since 2009, describes this as more of a “discovery” project than one with a narrow hypothesis.

Teague is intrigued by the unpredictability of the work, an aspect that she says sets research apart from typical lab experiments.

“In lab, you have a procedure, and if you follow the protocol you can easily predict what the results are going to be,” she says. “The research is definitely more interesting, because you don’t know what’s going to happen, and once you get some results you still have to figure out what those results mean.

“In my laboratory courses, if you were learning about DNA, a lot of times they will give you the DNA directly. In our research, it was ‘here’s the piece of liver and we’ll do a million steps in between and eventually remove the DNA from cells.’”

A female college student in navy coveralls stands next to a sign at the USDA sheep station in Idaho.

During her trips with Brown to the USSES in Idaho, in April and June, Teague got to be directly involved with the process, from the sheep’s slaughter all the way to tissue collection and DNA extraction.

“When we dissect organs in the lab, they feel tough because they have been preserved,” she says. “Dissection involving fresh tissue and organs was different. I got to go into the body cavity to directly collect tissues and organs. After already learning about the mammalian body in anatomy and physiology class, it was nice to see it again from a very different perspective and say, ‘So this is what a fresh lung really looks like.’”

Blood and multiple organs and tissues were gathered from a group of ewes, resulting in hundreds of samples to be analyzed.

“Finding fetal DNA will be like trying to locate a needle in a haystack,” explains Erika Niland, a Wingate associate professor who is lending her expertise to the project by performing a technique called real-time polymerase chain reaction.

“Using real-time PCR, you can quantify the amount of DNA you present in a sample, so we should be able to detect extremely small amounts of DNA,” Niland says.

Working with others

Brown says Niland is teaching both her and Teague how to use the PCR technology, which many biology professors at Wingate use with their research. She says collaboration within small biology departments like Wingate’s is integral to research success.

“Physiologists, like myself, typically try to answer questions from a much larger perspective, so learning new laboratory techniques from and discussing project ideas with my colleagues who focus on molecular aspects of biology has been great,” Brown says. “We really have to rely on one another at times, as so much of the technology and scientific knowledge changes from year to year. We have nice diversity here, even though our school is small. It makes it very easy to collaborate with colleagues.”

Teague is thrilled by the opportunity to work with multiple scientists, both at the USSES and at Wingate, and says the research is helping her develop skills she’ll need as a physician.

“Conducting research will increase my ability to think like a scientist, which is essentially what physicians have to do each day,” Teague says. “In order to understand and diagnose a patient, I must be able think critically and analyze and interpret data. It’s like putting the pieces of a puzzle together.”

She says the research is also boosting her scientific literacy as she spends time reading, writing and presenting scientific data.

Next spring, she’ll take her findings to Georgia to present them at the National Conference on Undergraduate Research.

July 25, 2018

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