April 23, 2020
A team of Michigan Medicine researchers in the Ginsburg Lab is applying its expertise in genome-scale CRISPR screening to identify novel genetic interactions relevant to the COVID-19 viral infection.
Their project “Whole-Genome CRISPR Screen for Cellular Determinants of COVID-19 Infection” is utilizing CRISPR technology (a tool used to edit genes), which enables them to engineer hundreds of millions of precise changes in the human genome and then identify those changes that control ACE2 production.
Brian Emmer, MD, PhD, Assistant Professor of Internal Medicine in the Division of Hospital Medicine, leads the project, along with principal investigator David Ginsburg, MD, James V. Neel Distinguished University Professor and Warner-Lambert/Parke-Davis Professor in the Departments of Internal Medicine (Division of Genetic Medicine), Human Genetics, and Pediatrics.
“The virus that causes COVID-19 establishes infection by entering host cells through a receptor called ACE2,” said Dr. Emmer. “Very little is understood, however, about the pathways that determine how much ACE2 is made by the cell.”
The team will be screening for mutants with decreased cell surface abundance of the ACE2 receptor used by the COVID-19 virus to enter cells, as well as mutants with decreased internalization of the COVID-19 virus glycoprotein that binds ACE2 to mediate viral entry. In addition, they are collaborating with Michigan Medicine virology laboratories to develop a screen for mutants that are resistant to virus-mediated cytotoxicity.
“Our hope," said Dr. Ginsburg, "is that we can identify vulnerabilities of the COVID-19 virus that we can then target with drugs that are already in clinical use."
Learn more about the wide range of Michigan Medicine research endeavors to study and address the coronavirus pandemic.
