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Using CRISPR, biology major seeks link between metabolic syndromes and muscular diseases

by Luanne Williams
A female professor and female student work on a chemistry experiment.

When friends ask Kirby VonEgidy what’s she’s doing this summer, she keeps it simple: “I tell them I am doing research on two proteins that affect the heart.” What the biology major from Marshville doesn’t explain is that she is using state-of-the-art genome editing technology (CRISPR Cas9) to try to find connections between metabolic syndromes and muscular diseases.

Assistant biology professor NaTasha Schiller believes the research she and VonEgidy are doing will lead to publications in national journals, with VonEgidy as first author, a rare privilege for an undergraduate. But before she can take advantage of big opportunities to present her findings, VonEgidy must first focus on the small. She is working through a series of tasks with cells from the calf muscle of a mouse and strands of DNA edited to suppress two particular protein-coding genes: nuak1 and nuak2.

Schiller explains the big picture before getting too deep into the molecular science. “Metabolic dysfunction syndromes such as Type 2 diabetes are rising in human populations, and patients with these syndromes are at increased risk for cardiovascular disease,” she says. “While a relationship between nutrition and heart disease in mammals is known to exist, the exact molecular mechanism resulting in a diseased muscular state is still unknown.”

She and VonEgidy are focused on identifying specific relationships between the structure of muscle fibers and how cell mitochondria function. Once they better understand the role that muscle-specific proteins play in regulating metabolism, they may be able to find new links between myopathies and metabolic syndromes that would lead to new medications.

Step by step

VonEgidy’s first task was to take mouse myoblast cells and grow them in the lab. Then, using knowledge she had gained in Schiller’s Bio 340 class along with open-source bioinformatics, she developed molecular tools to target nuak1 and nuak2.

“What we have to do is create specific DNA sequences that the cell can read and make a protein from, like a recipe,” she says. “The recipe is telling the cells to create a protein that is foreign to them. That protein, with the help of another DNA sequence, matches up to the nuak1 or nuak2 gene sequence.

A female college professor uses a pipette to work on an experiment.

“Then we’ll put this ‘machine’ inside the mouse cells to try to disrupt some proteins by blocking the DNA from being transcribed. If we can disrupt them, then we can see what they do, because we’ll see what they didn’t produce. It’s kind of like if you had a car and didn’t know how it worked so you unhooked the brake, you’d find out what the brake did by its absence. We have to make the protein not work to see what it normally does in the cell.”

First they will permanently “turn off” the nuak1 gene, disrupting its protein production, and observe cell growth in the sarcomere, the basic unit of striated muscle tissue. Simultaneously, in other cells, they will turn off the nuak2 gene and observe any changes in cell structure. And finally, they will turn both the nuak1 and nuak2 genes off at once, in the same cells, looking to see if the cells organize properly in the absence of both proteins.

Not only will the results – whatever they reveal – be of interest to those in the field of molecular medicine, but Schiller says VonEgidy’s tools will be used by her next Bio 340 class, who will move the research forward by applying the techniques to mouse-heart cells.

VonEgidy, who has her sights set on becoming a pediatric oncologist, is thrilled by the prospect of laying the groundwork for more students to get a stab at the kind of research she is doing. 

“The way Dr. Schiller structures her class gives every student a lot of independence,” she says. “The labs are not just about following a protocol and getting a result. She gives students the freedom and ability to design their own research. This summer, I’ve learned so much, even from my mistakes or when things didn’t go as planned.”

A personal detour

VonEgidy is no stranger to life’s detours. Within a short time, when she was 15, she went from being a competitive dancer to using a wheelchair.

“I have a chronic illness that changed my life completely as a sophomore in high school,” she says, describing her battle with postural orthostatic tachycardia syndrome (POTS). “I went from a high-achieving student-athlete to a bedridden sick girl who lived in and out of hospitals for over three years.”

A rare condition that affects circulation as well as the autonomic and sympathetic nervous systems, POTS attacked VonEgidy after a traumatic injury to her spine. Although she says she felt like a guinea pig as doctors tried different treatments to help her, she sees a bit of a silver lining in the cloud of chronic illness.

“It has been a long journey for me but one that I am somewhat grateful for,” she says. “Having dealt and still dealing with medical issues gives me a unique perspective that I believe will make me a better doctor. Not only will I be able to sympathize with my patients, but I will be able to empathize with them as well.”

She’s also thankful that she wound up at Wingate, a school that wasn’t on her radar until she became ill and needed to stay close to home.

Winding up a Wingate

Portrait of chemistry student and professor at lab table.

“I had always thought I would go away to school, a larger school,” she says. “I came into Wingate with the intention of transferring after my first year. But I fell in love with it. It was just big enough that I saw new faces all the time, but small enough to build relationships with my professors.”

Her condition improved enough in the summer after high-school graduation that she had ditched her wheelchair and walker just days before showing up to her first class as a freshman. But she was still using a cane. 

“I was nervous, and I remember in my very first class the professor asked us to share what is one thing you learned this summer,” VonEgidy says. “I said, ‘I learned to walk.’”

Although her health has improved greatly – she is on Wingate’s cheerleading team, is vice president of the Student Government Association and is active with her sorority – she still deals with fluctuating blood pressure and other POTS-related issues that can interrupt her ability to study and sometimes even land her in the hospital. She also travels out of town monthly for medical care.

“I have so much support here,” VonEgidy says. “You hear the One Dog thing, but really it is not cliche.”

Beyond the day-to-day support and the opportunity to do grant-funded research, Wingate has also afforded her a leg up as she applies for med school. The University’s partnership with the Edward Via College of Osteopathic Medicine has given her a chance to apply to the Rocovich Scholars Program, which would fast-track her med-school application and enable her to sidestep the Medical College Admission Test.

Whether she’s named a Rocovich Scholar or not (she won’t know until late September or early October), VonEgidy doesn’t doubt her calling into medicine.

“Having an incurable illness is why I want to enter the research field,” she says. “I want to help research and discover more about unknown illness. The more that is discovered about the body and its cellular and metabolic processes, the more knowledge we will have to develop cures.”

VonEgidy and Schiller are among seven professor-student pairs whose summer research has been funded by a Reeves grant.

Aug. 12, 2019