‘Molecular Motors’ Research Could Drive New Antiviral Treatments

A color-enhanced transmission electron micrograph (TEM) shows viral particles magnified 110,000 times. Viruses—like those Pew scholar Brian Kelch studies—infect various living organisms, including humans and bacteria.

© Biophoto/Science Source

Viral genomes are protected by a protein shell or “capsid.” For some viruses, the capsid is assembled first, with viral DNA then pumped and packaged into it—an essential step in the viral life cycle. The macromolecular machine performing this pumping is one of the strongest biological motors known: Pressure inside the tight confines of a filled capsid is 10 times that of bottled champagne.

Brian A. Kelch, Ph.D., a 2014 Pew biomedical scholar and assistant professor in the Department of Biochemistry and Molecular Pharmacology at the University of Massachusetts Medical School, is exploring how this motor recognizes viral DNA and pushes it into the capsid. His team’s work aims to reveal details about the operation of this motor and could uncover new targets for antiviral therapies that block a crucial step in the assembly of viral particles.

“The molecular processes we study will reveal principles of how biology works at the atomic level,” says Kelch. “By understanding biology at its most basic level, we can design new drugs that can alter biological events in ways that can alleviate disease and other human suffering.”

The Kelch lab has developed a model of a thermophilic virus to help demonstrate how this type of virus packages its genome into a protective protein shell, or capsid. The model re-creates the virus' motor (represented as green gears and twirling blades) responsible for pumping the genome and cleaving the DNA at the start and end of packaging.

© Brian Kelch

Kelch enjoys sharing research discoveries with the other scientists who work in his lab.

“There’s nothing like making a discovery with graduate students and seeing their faces light up as they realize they’ve uncovered something big,” Kelch says. “Sharing that sense of excitement with researchers still finding their way as scientists feels great.”

Engagement with others about research in his field and beyond—and the caliber of minds in Pew’s biomedical scholars community—is also what drew Kelch to the program. 

“I get so inspired by others’ work,” Kelch says. “It’s really a rejuvenating experience to talk to other Pew scholars.”

At a time when it has been difficult for funding to keep pace with the influx of scientists with degrees in biomedical sciences, Kelch emphasizes the importance of supporting early-stage investigators as they work to build a strong case for the direction of their research. He also stresses the critical need for basic molecular research, because treatments can come from unlikely places, often through understanding biology’s most fundamental processes.

“We never quite know which new discovery is going to lead to a real shift in how we treat disease,” says Kelch.

Kara Coleman directs The Pew Charitable Trusts’ biomedical programs, including the biomedical scholars, Pew-Stewart Scholars for Cancer Research, and Latin American fellows programs.