The goal of our project is to understand the molecular remodeling of the host cell and mitochondria caused by the ORF9b SARS-CoV-2 protein. ORF9b is a protein encoded by the SARS-CoV-2 virus that physically interacts with TOMM70 on the surface of mitochondria. How this protein remodels mitochondrial function during infection is unclear. To this end, we have performed acute infection experiments in lung epithelial cells using SARS-CoV-2 and genetically engineered viral variants lacking functional ORF9b and have extracted RNA and protein for OMICs analyses. The transcriptional profiling that will be explored in these uninfected and infected human cells will be paired with ongoing proteomic studies. We seek to define how ORF9b targets mitochondria and rewires host metabolism and cell signaling during infection.
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