When University of Vermont College of Medicine graduate student Benjamin King travels to France supported by a prestigious Chateaubriand Fellowship, he’ll be bringing along important questions about how the Arenavirus – a family of viruses endemic in rodents that has led to human disease outbreaks in Nigeria, Argentina and other countries – hijacks normal cell function. About seven months later, he hopes to return with some answers, as well as new skills, in leading-edge microscopy and data analysis that he can share with his colleagues and mentors in the UVM Cellular, Molecular and Biomedical Sciences Program (CMB).

King, a fourth-year CMB Ph.D. student working with UVM Assistant Professor of Medicine Jason Botten, Ph.D., applied for the Chateaubriand Fellowship in Science, Technology, Engineering & Mathematics on the recommendation of Ralph Budd, M.D., professor of medicine and director of immunobiology, with whom he worked several years ago on a summer research project. Now that King is nearing the end of his Ph.D. program, he thought the time was right to apply. The fellowship, offered by the French Embassy’s Office of Science and Technology, seeks to create lasting links between French scientists and scientists working abroad, both to share knowledge and hopefully recruit scientists to faculty and post-doctoral positions in France. The student is asked to propose a host lab, so King started looking into virology researchers in France. The Institut Pasteur in Paris – and in particular the lab of Christophe Zimmer, Ph.D., a principal investigator and head of the Imaging and Modeling Unit – rose to the top.

“I looked at the questions they were asking and the techniques they were using,” he says. “They are doing some things that would be impossible for me to do here.”

Relying on his pedigree as a scientist and the Institut Pasteur’s expertise in computational modeling, King’s research goal is to gain a better understanding of how the Arenavirus takes over a host cell, knowledge that could lay the groundwork for eventual development of an antiviral treatment.  

“I come with the hypothesis and the wet bench skills,” he says. “They have the data acquisition and the analysis side.”

The Arenavirus is first transmitted to humans through contact with the excretions or materials contaminated with the excrement of an infected rodent. In some cases the virus then spreads through human-to-human contact, causing outbreaks of serious diseases like Lassa Fever, a virus prevalent in West Africa that infects 100,000 to 300,000 people annually. And since no treatment exists, Arenavirus has been identified as a potentially dangerous bioterrorism weapon.

To discover the inner workings of the Arenavirus, super resolution microscopy may provide crucial clues. This relatively new technology allows scientists to visualize the tiny proteins that make up living cells, which exist on a scale too small to see with traditional microscopy. UVM’s STORM Microscope – housed in the UVM Microscopy Imaging Center – is one example of super resolution microscopy. The Institut Pasteur uses a similar technology, called PALM, but they are experimenting with a new technique that adds epitope tags – a short sequence of amino acids – to a protein of interest to help to visualize it, hopefully introducing less disruption to the normal functioning of the protein than methods used previously. The goal is to understand what happens at the molecular level when the Arenavirus takes over a host cell, and use computer modeling to come to conclusions.

Since there’s a “high learning curve” to working with large data sets and computational modeling, King looks forward to working closely with researchers who have this expertise, noting that it will be invaluable both for his research and to bring back to his program at UVM.  

Botten, who is King’s thesis advisor, says it’s not only a great honor for King to have received the fellowship, it’s an opportunity for his lab to collaborate with “one of the world’s leading experts in super resolution microscopy.” King’s time with the Institut Pasteur creates an ongoing relationship that links the research the Botten lab does into the biology of highly pathogenic viruses with “some of the most cutting edge technology in the world.”   

“We get to answer biological questions in our studies,” Botten says. “And [the Zimmer lab] can use some of what we’re doing to test the technology.”

Despite the challenges, King has the skills and disposition to take on interdisciplinary research that spans continents, says Budd. As one of King’s mentors, Budd wrote in his recommendation letter to the French Embassy: “Mr. King is not only a highly intelligent and independent thinker, and dedicated and meticulous with his experiments … [he] is simply one of the finest graduate students I have observed in my 25 years at the University of Vermont.”

A Middlebury College graduate, King is no stranger to France. He spent one year teaching English at a public high school in the country, and completed a one-year master’s program there, before returning to the U.S. for his Ph.D. work.

For this trip to France, King will be heading to Paris, to one of the oldest and most well-respected research institutions in the world. With roots that date back to 1887, the Institut Pasteur includes 2,600 scientists, researchers, and other staff, with over 60 nationalities represented. Interdisciplinary teams give priority to infectious disease research, including viral diseases like hepatitis and haemorrhagic fever, bacterial diseases including cholera and tuberculosis, and parasitic disease. The Institut boasts many Nobel Prize winners – eight since 1908 – and was the first to isolate the HIV virus in 1983.

This is exciting for Botten, who calls the work King is doing “pioneering” for its application of super resolution microscopy to the problem of Arenavirus functioning within a host cell. The Chateaubriand Fellowship promises to advance science by crossing cultural boundaries and sharing knowledge.

 “There’s the potential to maintain a relationship that takes advantage of each other’s strengths,” King says. “A lot of what we do is complementary.”

Learn more about the Chateaubriand Fellowship.

PUBLISHED

06-09-2014
Erin E Post