James Weger-Lucarelli has been awarded a grant to develop easy-to-use tools and techniques that will allow more researchers to study RNA viruses and their mutations. 

Weger-Lucarelli, assistant professor in the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland College of Veterinary Medicine, received the $150,000 grant from the National Institute of Allergy and Infectious Diseases.

"Unlike any other organism, RNA viruses like SARS‑CoV‑2 and dengue have an incredible capacity for adaptation. They have the ability to evolve rapidly, jump from one host to another, and to mutate to become more transmissible or deadly,” said Weger-Lucarelli. 

To study RNA viruses, researchers start by creating an infectious clone, a copy of the virus’s genome that is transformed from RNA into DNA. Once in DNA form, researchers can edit the genome’s sequence — for example, when creating a vaccine, they might delete sections of the genome to weaken the virus. Through this process, researchers can both create mutations and study naturally-occurring variants. 

However, the RNA-turned-DNA needs to be stored, or amplified. The current go-to method is to store the DNA sequence in bacteria, but it’s not a perfect system. 

To study viruses in this way, researchers need to find a collaborator capable of conducting this process. In addition to that barrier, the virus can also be toxic to the bacteria, leading to changes in the DNA that alter the virus. 

"Bacteria were previously both a necessity and a problem — very few researchers could do this work because it required a lot of not just technical skill, but there was an art to it,” said Weger-Lucarelli.  “Very few labs could develop infectious clones for certain types of RNA viruses like SARS-CoV-2 and other public health concerns,” 

"This project is to develop a system in a way that's very straightforward and simple so that more research groups can do this. This would then open up possibilities for other researchers who haven't been able to do this kind of work." 

Instead of using bacteria, Weger-Lucarelli plans on developing new tools and techniques using a process called rolling circle amplification. Rolling circle amplification uses PHI-29 polymerase, a protein from a virus that infects bacteria, to amplify the virus in a tube with no bacteria required. 

"Our goal is that other labs can do this kind of research, and in the long term, it will hopefully lead to more basic discoveries and more vaccines." 

Written by Sarah Boudreau M.F.A. '21, a writer with the Virginia-Maryland College of Veterinary Medicine


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