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$1.6 million grant helps FIU researcher target protein needed for replication of infectious viruses, bacteria

$1.6 million grant helps FIU researcher target protein needed for replication of infectious viruses, bacteria

February 10, 2021 at 10:25am

An FIU researcher was awarded nearly $1.6 million to investigate new ways to battle deadly diseases including COVID-19 and future pandemics.

Yuk-Ching Tse-Dinh, director of FIU’s
Biomolecular Sciences Institute, will use the support from the National Institute of General Medical Sciences of NIH to unravel how certain proteins —topoisomerases — are used to untangle DNA and RNA while they replicate.

Stopping the replication process can keep viruses from converting cells into virus factories and it can keep harmful bacteria from spreading.

Even the earliest and smallest forms of life on Earth — archaea and bacteria — rely on topoisomerase protein TOP1A to spread. Some bacteria have become immune to today’s antibiotic drugs so finding a new drug against a target such as TOP1A to protect people from these superbugs is crucial.

“It’s not only to advance our understanding of how life starts and is maintained,” Tse-Dinh said. “It also has implications for the discovery of important therapeutics for treatment of multi-drug-resistant bacteria and viral pathogens that may come up in future pandemics.”

The problem of drug resistance is particularly vexing. The Centers for Disease Control and Prevention noted in a 2019 report that 2.8 million antibiotic-resistant infections occur in the U.S. annually resulting in 35,000 deaths.

Of particular interest for Tse-Dinh with this renewal is the opportunity to further explore a human protein, TOP3B, that belongs to the same topoisomerase family as bacterial TOP1A. This protein is used by flaviviruses and coronaviruses including Dengue, Zika and COVID-19 to turn infected human cells into virus factories.

The hope for Tse-Dinh is to help develop a drug that blocks a coronavirus’ ability to hijack host TOP3B to aid in its replication. Such drug can potentially be used in a cocktail in tandem with other drugs that block the viral proteins or modulate the human immune response.

Funding from this project also will cover collaborator’s work at the Argonne National Lab to use X-ray crystallography to provide a map for the potential drug binding sites on topoisomerase proteins in the drug discovery process.  

This MIRA grant, awarded for five years, provides researchers with greater stability and flexibility, enhancing scientific productivity and the chances for important breakthroughs. This marks the ninth time Tse-Dinh has received a grant award from NIH to conduct her research on topoisomerases.

In addition to leading the Biomolecular Sciences Institute, Tse-Dinh also directs the university’s Translational Molecular Discoveries initiative, an emerging pre-eminent program.