As labs reopen across the University of Rochester, two biologists have received expedited federal funds to follow the interaction of coronavirus with proteins in human cells. The funding is part of the National Science Foundation’s Rapid Response Research program for high-priority projects.
Dragony Fu, an assistant professor of biology, and Jack Werren, the Nathaniel and Helen Wisch Professor of Biology, join others worldwide to learn more about the coronavirus. Fu and Werren will tap their expertise to research proteins in infections from COVID-19.
The goal: to understand the biological mechanisms and proteins involved in COVID-19 infection in order to develop effective treatments and vaccines.
Fu’s lab had been studying a human protein, TRNA Methyltransferase 1, before the pandemic hit. Researchers at the University of California, San Francisco recently discovered that the main COVID-19 protease, proteins that cut the virus’ proteins in smaller pieces for infection, interacts with TRMT1.
Photo by J. Adam Fenster / University of Rochester
“The central goal of our lab is to understand the functions of proteins that modify RNA,” Fu says. “TRMT1 happens to be one of the main RNA modification proteins we study, so it was quite serendipitous that it is connected to the COVID-19 virus because we have already established tests to measure TRMT1 function in human cells.”
The primary role of RNA in cells is to help make proteins in the human body. In collaboration with the French National Centre for Scientific Research, Fu is studying why the coronavirus interacts with TRMT1 and how that affects the virus and human cells. He posits that the virus protease cuts TRMT1, preventing it from its normal modification of RNA, ultimately compromising RNA’s function in protein synthesis.
Fu and his team plan to deliver the viral protease gene into human lung cells and use antibodies to detect TRMT1 to see if the protein in fact is being altered by the virus.
“We will be able to use this knowledge to discover new connections between the virus and the host human cell,” Fu says. “These novel links could serve as potential therapeutic targets for treatment of COVID-19 infection.”
Werren’s lab is going to identify interactions between an enzyme receptor located on call surfaces—the Angiotensin-converting enzyme 2(the virus binds to this receptor upon entry)—and other human proteins involved in health issues linked to COVID-19 infection. Using his expertise in evolutionary rate correlation, he expects to identify proteins that may coevolve and interact with the ACE2 receptor on human cells. Werren is using the ERC approach to determine protein interactions relevant to severe symptoms of the disease.
“Our goal is to characterize these interactions further and quickly publish the findings, in case the information will be useful in identifying targets for therapeutic intervention,” Werren says.
Fu and Werren are two examples of several hundreds of researchers that have benefitted from NSF’s Rapid Research Response program. As of June 1, the agency had funded more than 800 research efforts across the nation, exploring issues related to personal protective equipment to epidemic spread models and biological interactions. These awards facilitate interdisciplinary collaborations.
So far, UR has received five Rapid Research Response grants related to COVID-19. Rochester Institute of Technology has earned one.
In separate news, the UR Medical Center was awarded $24.3 million from the National Center for Advancing Translational Science at the National Institutes of Health. The funds are expected to help URMC to continue its efforts to turn scientific discoveries into health benefits faster. The chunk of federal monies brings URMC’s total funding from NCATS to $132 million. In 2006, URMC was one of the first 12 institutions to receive an NCATS award nationwide.
“The COVID-19 pandemic highlights the clear and urgent need for biomedical research–especially translational research,” said University of Rochester President Sarah Mangelsdorf, in a statement. “As one of the nation’s leading research universities, we are devoted to advancing scientific understanding and promoting health and this award will help us continue those efforts.”
The award continues funding for UR’s Clinical and Translational Science Institute, which aims to help researchers rapidly translate discoveries into therapies.
Smriti Jacob is Rochester Beacon managing editor.