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Student Pursues Veterinary Research and Helps Make Zika Discovery

November 23, 2016

Hannah Laurence (on right) explains her research with a conference participant.

Hannah Laurence (on right) explains her research with a conference participant.

Third year student Hannah Laurence took a big step this past year in her journey to become a veterinary research scientist. Not only did she complete a year-long program as a Howard Hughes Medical Institute (HHMI) fellow (one of 68 in the nation), but the biomedical research study she participated in recently appeared in the journal Science, published by the American Association for the Advancement of Science.

Laurence worked in the laboratory of Professor Jeff Kieft in the Department of Biochemistry and Molecular Genetics at the University of Colorado School of Medicine, where the research team discovered the molecular process used by the Zika virus to “hijack” cells and potentially how the virus makes molecules that are directly linked to disease. The discovery shows that a part of the Zika virus’s RNA genome folds up into a complex 3D structure that leads to the production of smaller RNA fragments, which in related viruses are directly associated with disease.

“Stepping out of the veterinary curriculum for a year was challenging but ultimately an extraordinary experience,” Laurence said. “I have an incredible amount of support from our faculty here at UC Davis, and I am grateful to those who have helped me in pursuing my dream of becoming a veterinary research scientist.”

Laurence grew up in San Francisco, riding horses most weekends. By high school, she figured on becoming an equine veterinarian. After receiving a B.S. in microbiology and a B.A. in Spanish from Colorado State University, Laurence entered the UC Davis School of Veterinary Medicine in 2013. Her first year foundations course included a section on pathology where she found a perfect match for her interests.

“As an undergrad in microbiology, I was fascinated by infectious diseases,” Laurence said. “Pathology seemed to be a way to link my interests in pathogenesis and clinical medicine.”

At that point, Laurence knew she wanted to follow a career path that would allow her to pursue some avenue of research, so she began exploring various opportunities, including the Students Training in Advanced Research program. In the summer between her first and second years of veterinary school, Laurence worked on a STAR project with Dr. Munashe Chigerwe involving neonatal calves and failure of passive immunity. She also considered the Veterinary Scientist Training Program, which allows DVM students to step out of the curriculum to obtain a Ph.D. and then step back in to complete their DVM training.

“I wasn’t quite ready to break up veterinary school for four to five years though,” she said.

Dr. Isaac Pessah, associate dean for Research and Graduate Education, suggested she look into the prestigious Medical Research Fellows Program through the HHMI. One of the attractive aspects about the program to Laurence was that she could choose a mentor anywhere in the country. After extensive searching, Laurence connected with Kieft in Colorado. Following numerous emails, phone calls and a visit to meet with all the researchers in the laboratory, Laurence choose to work in his lab for a year, focusing on flaviviruses such as West Nile and dengue.

“I was worried about losing everything I’d learned in my first two years of veterinary school,” Laurence said. “I had to move to a new place, build new relationships and be a scientist for a year. It was challenging but really fun!”

A few months after starting her fellowship in the fall of 2015, Laurence began seeing a lot of reports about Zika virus. Coincidentally, Dr. Benjamin Akiyama, a postdoc in Kieft’s lab, had been working on a project to determine the structure of Zika virus. If the lab team could also determine the molecular process used by the Zika virus to “hijack” cells, they would have a much stronger basis for a scientific paper that could elucidate the structure and function of Zika virus. By last November, Laurence had switched gears to focus more on Zika, while continuing her work with West Nile and dengue.

Discovering How Zika Works

Because viruses cannot reproduce on their own, they must infect cells and take over the cell’s biological machinery to make more copies of themselves. To do this, viruses use many molecular strategies.
Zika is an example of a virus that does not store its genome in DNA, rather it uses a related molecule called the viral genomic RNA. Viruses related to Zika, such as West Nile and dengue, are known to produce a set of smaller RNAs that are directly linked to disease, as well as long genomic RNA. Before this study, this process had not been explored with the Zika virus.

The researchers, led by Akiyama from the Kieft lab, showed that Zika infection leads to production of these smaller RNAs in several types of cells. In addition to demonstrating how the Zika genomic RNA “folds up” and blocks a powerful cellular enzyme that normally destroys RNA, the research team used an advanced technique called x-ray crystallography to solve the structure of this folded-up RNA segment. By altering the Zika virus genomic RNA, the team was able to disrupt this structure and eliminate the production of the potentially disease-causing small RNAs. The discoveries also may be broadly applicable to understanding and preventing other related viruses such as Dengue, West Nile, Japanese encephalitis and yellow fever.

“We were able to prove that Zika does behave similarly to other flaviviruses by hijacking cells in a similar way,” she said. “Our hope is that by understanding how Zika virus works, we can find ways to combat it through a vaccine or therapeutics. This is a very preliminary, yet critical step in a long process. To fight the virus, we need to understand how it works.”

Laurence’s experiences are exactly why Pessah remains excited to see students pursue research opportunities.

“Ms. Laurence exemplifies the exceptional preparation and dedication of our students to not only address real word challenges, but also make fundamental research contributions that have translational impact,” Pessah said.

In addition to working in the Kieft lab, part of Laurence’s experiences during her year-long fellowship was attending six different research conferences around the country, including the Merial-NIH National Veterinary Scholars Symposium. Networking at the conferences and sharing her research proved a big part of the fellowship and helped her bond with the HHMI fellows.

“There was only one other veterinary student among us, so the other fellows were always very curious to talk with us about what our schooling was like,” Laurence said.

Coming back into veterinary school proved a little challenging in the beginning for Laurence because she had to integrate into a new class of students, but instead of one family of classmates, she now belongs to two. She credits the fellowship as a valuable experience in terms of professional and personal growth.

“My year in the lab fostered independent thinking and creativity. I had to approach problems from different perspectives—that can’t be taught in the classroom,” Laurence said.” I feel like I came a long way in becoming a truly analytical scientist and medical professional.”