Michele Barry

Biography

Professor, Dept. of Medical Microbiology & Immunology Canada Research Chair Tier I Howard Hughes International Scholar Executive Committee Member - Li Ka Shing Institute of Virology Journal of Virology - Associate Editor (2011-2013) PLOS Pathogen Editorial Board - Associate Editor AHFMR Senior Scholar CIHR - New Investigator Member, Faculty Research Committee, Faculty of Medicine and Dentistry Immunology Network Council Member

Research Interest

Hide and Seek: Unraveling the Strategies Viruses Use to Evade Detection During the course of evolution, viruses have adapted to ensure their own survival by exploiting and manipulating cellular signaling pathways, thereby preventing the host from detecting and destroying them. The study of viral immune evasion can identify previously unknown aspects of the host immune response. To understand more about virus:host interactions we study poxviruses. Poxviruses are a family of double-stranded DNA-containing viruses that replicate within the cytoplasm of the cell and encode over 200 proteins. The most notorious member of the family is variola virus, which prior to eradiation was the causative agent of smallpox. This family of viruses has proven to be extremely adept at counteracting host immune responses and interfering with host cell signaling pathways. Our main focus is to understanding how poxviruses manipulate cellular signaling pathways and specifically how poxviruses regulate cell death and exploit the ubiquitin proteasome pathway.   Poxvirus Inhibition of Cell Death- Research in my laboratory is currently focused on understanding how members of the poxviruses family evade apoptosis. Apoptosis is an inherent cellular property that can be triggered by a variety of external stimuli including cytotoxic T lymphocytes and in some instances virus infection itself. The impairment of apoptotic pathways is a key event controlled by many pathogens. Therefore, in order to ensure their own survival, viruses have evolved strategies that target crucial components within the apoptotic cascade and have proven to be important tools for dissecting apoptotic pathways. Several years ago we identified a novel anti-apoptotic protein, F1L, encoded by vaccinia virus (PNAS 100:14345 ). Despite lacking apparent sequence similarity to members of the cellular Bcl-2 family, F1L localizes to the mitochondria and inhibits the release of cytochrome c. F1L functions by inhibiting both Bak and Bax, the key pro-apoptotic proteins that are essential for initiating cell death (J. Biol. Chem. 281:39728). In contrast to F1L, the avipoxviruses, which include fowlpox virus, are the only poxviruses known to encode proteins with obvious Bcl-2 sequence homology (J. Virology 81:11032). We have found that fowlpox virus inhibits apoptosis by inactivating multiple pro-apoptotic Bcl-2 proteins including some BH3-only proteins as well as Bax and Bak (J. Virology 83:7085).