Grant: Project Grant

In our previous CIHR grant, we conducted a genetic screen to identify novel genes involved in antibody production for effective immune protection. Using mouse cells, we discovered Fam72A, a gene that produces a protein causing degradation of the UNG2 mouse protein that is involved in DNA repair. By causing UNG2 degradation, FAM72A prompts the production of antibodies that bind very tightly to viruses and other pathogens. As a result, FAM72A plays an important role in ensuring that the best antibodies are produced to remove viruses and other pathogens from our bodies. Unlike mice and other mammals, including non-human primates, humans have expanded this gene family to include four closely-related genes called FAM72A-D. The function of each of these genes is not known. This proposal will explore how this relatively unknown gene family is involved in antibody production, and the role of the four closely-related FAM72A-D proteins in human biology. We hypothesize that some of these proteins are involved in degrading a related protein of UNG2 that is expressed in Herpes viruses. These viruses encode an UNG2 homologue required for viral growth and if FAM72A-D bind to and degrade viral UNG2s, they will restrict viral growth. We will also assess other functions of FAM72 proteins in human B cell biology. This proposal seeks to determine the function and role in immunity of this novel and poorly defined FAM72 gene family, contributing to the study of immunity against infectious diseases and the identification of molecular mechanisms that impact DNA repair and genetic mutation in cancer cells.