Research Projects
Proteomics of Virus-Host Interaction
Viruses are obligate cellular pathogens and therefore many cellular proteins are critical for viral infection, replication, and release from a host cell. Using cutting edge proteomics approaches, we are seeking to identify cellular pathways that are involved with the infection process. The significance of this work is two-fold: the basic biology of viruses can be elucidated and novel targets for antiviral agents can be identified.
Noroviruses are a serious health and economic concern world-wide and are responsible for > 23 million infections per year in the USA alone. Despite the obvious importance of this group of viruses, much remains to be learned about their biology. This is largely due to a lack of animal and tissue culture model systems. The recent development of a murine norovirus (MNV) that can be cultured was a major breakthrough. We have adopted this system and are using a two-level proteomics approach to elucidate pathways and proteins involved with MNV infection. At the systems level, 2D differential gel electrophoresis (2D-DIGE) is being applied to generate an overview of the global changes in the host proteome during infection. This is being complemented by activity-based screening of enzyme classes. Activity-based protein profiling (ABPP) is currently the only technique that can directly measure specific protein activity across a biological system. Current research is directed toward understanding the role of apoptosis in MNV infected cells at the level of the system and individual proteins that become activated during programmed cell death. Graduate student: Linnzi Furman. Undergraduate: Lena Peterson.
Publications
Ortmann, AC, Brumfield SK, Walther J, McInnerney K, Brouns SJ, van de Werken
HJ, Bothner B, Douglas T, van de Oost J, Young MJ, "Transcriptome analysis of infection of the archaeon Sulfolobus solfataricus with STIV." J Virol. 82(10):4874-4883, 2008.
Maaty, W.S.A, Ortmann, A.C., DlakiÄ, M., Schulstad K., Hilmer, J.K., Liepold, L., Weidenheft, B., Douglas,T., Young, M., and Bothner, B., "Characterization of the Archaeal thermophile Sulfolobus Turreted Icosahedral Virus validates an evolutionary link among dsDNA viruses from all domains of life." J. Virology 80(15):7625-7635. (2006)
Furman LM, Maaty WS, Petersen LK, Ettayebi K, Hardy ME, Bothner B., "Cysteine protease activation and apoptosis in Murine norovirus infection." Virol J. 2009 Sep 10;6:139
Personnel:
Brian Bothner
Keywords:
Biochemistry, Analytical, Chemical Biology, Proteomics
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