Chris Upton

Professor

Education B.Sc. Ph.D., London (England)

Email: cupton@uvic.ca

WWW Site:

General Virus Bioinformatics - databases and tools for analysis of viral genomes.

VBRC-Blog! My BLOG on Virology/Bioinformatics (not very active, see twitter)

Twitter id: twitter.com/cupton1

Research Interests

The primary focus of research in my lab is Viral Bioinformatics: The application of computer technology to the management of biological information. Computers are essential for gathering, storing and analyzing the vast amount of biological and genetic information that is being generated by new high-through-put technologies in the biosciences (DNA sequencing; DNA-chip; proteomics). The knowledge we gain from Bioinformatics research can be applied to a variety of research areas, including the process of gene-based drug discovery.

Specifically, my group is developing specialized software to help automate the process of genomic analysis and predicting gene function in large virus genomes (poxviruses, herpesviruses, baculoviruses). These large viruses have 100-200 genes and the function of many of the proteins produced by the viruses remains a mystery. We have used viral sequences to discover novel similarities with human genes and, conversely, known human proteins to predict the function of virus proteins. The software helps us analyze the numerous virus genomes that have recently been completely sequenced and also aids in the annotation of newly sequenced genomes. We have a strong interest in the evolution and structure of viral genomes.

We were part of a collaboration that designed and built the Poxvirus Bioinformatics Resource (http://poxvirus.org) and the Viral Bioinformatics Resource Center (http://virology.ca) . This project was funded by the National Institutes of Health USA and supported research by many investigators developing new vaccines and drugs targeted at virus infections.

In another collaborative study (with Dr Delano James at the Centre for Plant Health, Sidney, BC), we are looking at the genomes and evolution of economically important plant viruses including cherry mottle leaf virus, peach mosaic virus and plum pox potyvirus.

Driving the Bioinformatics work, is a longstanding interest in basic poxvirus virology. For many years we have been working on virus virulence mechanisms, and this has led to the identification of the function of several poxvirus proteins.

Selected Publications: (of 86 total- Nov '09)

• Clifford, M., Twigg, J. and Upton, C. (2009) Evidence for a novel gene associated with human influenza A viruses. Virology Journal 2009, 6:198.
• Alzhanova D, Edwards DM, Hammarlund E, Scholz IG, Horst D, Wagner MJ, Upton C, Wiertz EJ, Slifka MK, Früh K. (2009) Cowpox virus inhibits the transporter associated with antigen processing to evade T cell recognition. Cell Host Microbe. 2009 Nov 19;6(5):433-45.
• Marass, F. and Upton, C. (2009) KISSa: a strategy to build multiple sequence alignments from pairwise comparisons of very closely related sequences. BMC Research Notes 2009, 2:91.
• Da Silva, M. and Upton, C. (2009) Vaccinia virus G8R protein: a structural ortholog of proliferating cell nuclear antigen (PCNA). PLoS ONE 2009;4(5):e5479.
• Marass, F. and Upton, C. (2009) Sequence Searcher: A Java tool to perform regular expression and fuzzy searchers of multiple DNA and protein sequences. (BMC Research notes Jan 30;2:14).
• Chapman, D., Tcherepanov, V., Upton, C. and Dixon, L. 2008. Comparison of the genome sequences of non-pathogenic and pathogenic African swine fever virus isolates. J. Gen. Virol. 89, 397-408.
• Summer, E.J., Gill, J.J., Upton, C., Gonzalez, C.F. and Young, R. 2007. Role of phages in the pathogenesis of Burkholderia or ‘Where are the toxin genes in Burkholderia phages?’ Curr Opin Microbiol. 10(4):410-7.
• Osbourne, J.D., Da Silva, M., Frace, M., Sammons, S.A., Olsen-Rasmussen, M., Upton, C., Buller, R.M.L., Chen, N., Feng, Z., Roper, R.L., Lui, J., Pougatcheva, S., Chen, W., Wohlheuter, R.M. and Esposito, J.J. Smallpox vaccine Vaccinia virus: genomic differences between a virulent and a vaccine-like clone. Vaccine 25(52):8807-8832.
• Butler-Cole,C., Wagner, M.J., Da Silva, M., Brown, G.D., Burke, R.D. and Upton, C. 2007 An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein. Virology Journal 2007, 4:76 doi:10.1186/1743-422X-4-76
• Thomas, J.M., Horspool, D., Brown, G., Tcherepanov, V., and Upton, C. 2007. GraphDNA: a Java program for graphical display of DNA composition analyses. BMC Bioinformatics. 8:21.
• Tyler, S.D., Peters, G.A., Severini, A., Gray, M.J., Upton, C. and Tipples, G.A. 2007. Genomic Cartography of Varicella-Voster Virus: A Complete Genome Based Analysis of Strain Variability with Implications for Attenuation and Phenotypic Differences. Virology 359:447-58
• Sajic R, Lee K, Asai K, Sakac D, Branch DR, Upton C, Cochrane A. 2007. Use of modified U1 snRNAs to inhibit HIV-1 replication. Nucleic Acids Res. 35:247-55.
• Eaton, H.E., Metcalf, J., Penny, E., Tcherepanov, V., Upton, C. and Brunetti, C.R. 2007. Comparative genomic analysis of the family Iridoviridae: re-annotating and defining the core set of iridovirus genes. Virology Journal. 4:11
• Thomas, J.M., Horspool, D., Brown, G., Tcherepanov, V., and Upton, C. 2007. GraphDNA: a Java program for graphical display of DNA composition analyses. BMC Bioinformatics. 8:21.
• Da Silva, M., Shen, L., Tcherepanov, V., Watson C. and Upton C. 2006. Predicted function of the vaccinia virus G5R protein. Bioinformatics 22, 2846-50.
• Peters,G.A., Tyler,S.D., Grose,C., Severini,A., Gray,M.J., Upton,C. and Tipples,G.A. 2006. A full-genome phylogenetic analysis of Varicella-Zoster Virus reveals a novel origin of recombination between major circulating clades. J. Virol. 80, 9850-9860.
• Tcherepanov, T., Ehlers, A. and Upton, C. 2006. Genome Annotation Transfer Utility (GATU): Rapid annotation of viral genomes using a closely related reference genome. BMC Genomics 7:150 (13 June 2006)
• Lefkowitz, E., Wang, C. and Upton, C. 2006. Poxviruses: past, present and future. Virus Research, 117, 105-118.
• Li, G., Chen, N., Roper, R.L., Feng, Z., Hunter, A., Danila, M., Lefkowitz, E.J., Buller, R.M. L. and Upton, C. 2005. Complete coding sequences of the rabbitpox virus genome. J. Gen. Virol. 86, 2969-2977.
• Esteban, D. J., Da Silva, M. and Upton C. 2005. New Bioinformatics Tools for Viral Genome Analyses at Viral Bioinformatics – Canada. Pharmacogenomics 6, 271-280
• Da Silva, M. and Upton C. 2005. Host-derived pathogenicity islands in poxviruses. Virology Journal 2(1):30.
• Chen, N., Li, G., Liszewski, M.K., Atkinson, J.P., Jahrling, P.B., Feng, Z., Schriewer, J., Buck, C., Wang, C., Lefkowitz, E.J., Esposito, J.J., Harms, T., Damon, I.K., Roper, R.L., Upton, C. and Buller, R.M. 2005. Virulence differences between monkeypox virus isolates from West Africa and the Congo basin. Virology 340, 46-63.
• Da Silva, M. and Upton C. 2005. Using purine skews to predict genes in AT-rich poxviruses. BMC Genomics. 6(1):22.
• Whitney, J., Esteban, D. J. and Upton C. 2005. Recent Hits Acquired by BLAST (ReHAB): A tool to identify new hits in sequence similarity searches. BMC Bioinformatics. 6(1):23.
• Upton, C. 2004. Poxvirus Bioinformatics. In: Methods in Molecular Biology , 269, p347-370 Poxvirus Protocols. Humana Press.
• Lefkowitz, E. J., Upton, C., Changayil, S. S., Buck, C., Traktman, P., Buller, R. M. L. 2005. Poxvirus Bioinformatics Resource Center: a comprehensive Poxviridae informational and analytical resource. Nucleic Acids Res 2005 33: p. D311-D316
• Brodie, R., A.J.Smith, R.L. Roper, V. Tcherepanov, and C. Upton. 2004.Base-By-Base: Single nucleotide-level analysis of whole viral genome alignments, BMC Bioinformatics, 5, 96.
• Chen, D., M. Danila, R.M. L. Buller and C. Upton. Complete sequence and analysis of the ectromelia virus genome. Virology, 317, 165-186.
• Brodie, R., R. L. Roper, and C. Upton. 2004. JDotter: A Java Interface to Multiple DotPlots Generated by Dotter. (Bioinformatics, 20, 279-281)
• Roper, R.L., Slack, S., Hunter, A.W., Ehlers, A. and C. Upton. Poxvirus Orthologous Clusters (POCs): Toward defining the minimum essential poxvirus genome. J. Virology 77, 7590-6000.
• M. A. Marra, S. J. M. Jones, C. R. Astell, R. A.Holt , A. Brooks-Wilson, Y. S. N. Butterfield , J. Khattra, J. K. Asano, S. A. Barber, S. Y. Chan, A. Cloutier, S. M. Coughlin, D. Freeman, N. Girn, O. L.Griffith, S. R. Leach, M. Mayo, H. McDonald, S. B.Montgomery, P. K. Pandoh, A. S. Petrescu, A. G. Robertson, J. E. Schein, A. Siddiqui, D. E. Smailus, J. M. Stott, G. S. Yang, F. Plummer, A. Andonov, H. Artsob,N. Bastien, K. Bernard, T. F. Booth, D. Bowness, M. Drebot, L. Fernando, R. Flick, M. Garbutt, M.Gray, A. Grolla, S. Jones, H. Feldmann, A. Meyers, A. Kabani, Y. Li, S. Normand, U. Stroher, G. A. Tipples, S. Tyler, R. Vogrig, D. Ward, B. Watson, R. C.Brunham, M. Krajden, M. Petric, D. M. Skowronski, C.Upton, R. L. Roper. 2003. The Genome Sequence of the SARS-Associated Coronavirus. Science, Published online 1 May 2003.
• Ehlers, A., J. Osborne, Slack, S., R. L. Roper, and C. Upton. 2002. Poxvirus Orthologous Clusters (POCs). Bioinformatics 18, 1544-1545
• James, D., and C. Upton. 2002. Nucleotide sequence analysis of RNA-2 of a flat apple isolate of Cherry rasp leaf virus with regions showing greater identity to animal picornaviruses than to related plant viruses. Archives of Virology 147, 1631-1641.
• C. Upton, D. Hogg, D. Perrin, M. Boone and N. Harris, 2001. Viral Genome Organizer: A system for analyzing complete viral genomes. Virus Research 70, 55-64.
• M. Boone and C. Upton, 2000. BLAST Search Updater: A notification system for new database matches. Bioinformatics 16, 1054-1055.
• Hiscock, D. and C. Upton. 2000. Viral Genome Database: A tool for storing and analyzing genes and proteins from complete viral genomes. Bioinformatics 16, 484-485.
• Upton, C., 2000. Screening coding regions in poxvirus genomes. Virus Genes 20, 159-164.
• James, D., W. Jelkmann and C. Upton, 2000. Nucleotide sequence and genome organization of cherry mottle leaf virus and its relationship to members of the Trichovirus genus. Archives of Virology. 145, 995-1007.
• Brick, D.J., R.D. Burke, A.A. Minkley and C. Upton, 2000. Ectromelia virus virulence factor p28 acts upstream of caspase-3 in response to ultra-violet light induced apoptosis. Journal of General Virology. 81, 1087-1097.
• Chen, D., R.M. L. Buller, E.M. Wall and C. Upton, 2000. Analysis of host response modifier ORFs of ectromelia virus, the causative agent of mousepox. Virus Research. 66, 155-73.
• James, D., W. Jelkmann and C. Upton, 1999. Single primer pair designs that facilitate simultaneous detection and differentiation of peach mosaic virus and cherry mottle leaf virus. Journal of Virological Methods 83, 103-11.
• James, D., Jelkmann, W. and Upton, C. 1999. Specific detection of cherry mottle leaf virus using digoxigenin-labelled cDNA probes and RT-PCR. Plant Disease 83, 235-239.
• Brick, D.J., Burke, R.D., Schiff, L. and Upton, C. 1998. Shope fibroma virus RING finger protein N1R binds DNA and inhibits apoptosis. Virology 24942-51.
• Dickstein, R., Davies, P. C., Hoogland, D. S., Brick, D. J. and Upton, C. 1998. An Arabidopsis lipase-like gene within a sequence previously characterized as an intron. J. Biochem. Mol. Biol. & Biophys. 1, 265-273.
• Wall, E. M., Cao, J., Chen, N., Buller, R. M. L. and Upton, C. 1997. A novel poxvirus gene and its human homolog are similar to an E. coli lysophopholipase. Virus Research 52, 157-167.
• Cattell, K., Koop, B. F., Olafson, R. S., Fellows, M., Bailey, I., Olafson, R. W., and Upton, C. 1996. Approaches to detection of distantly related proteins by database searches. BioTechniques 21, 1118-1125. WWW version.
• Brick, D.J., M.J. Brumlik, J.T. Buckley, J. Cao, P.C. Davies, S. Misra, T.J. Tranbarger and C. Upton, 1995. A new family of lipolytic plant enzymes with members in rice, arabidopsis and maize. FEB Letters 377, 475-480.
• Upton, C. and Buckley, J. T. 1995 A new family of lipolytic enzymes? Trends in Biochem.Sci. 20: 178-179.
• Upton, C., Schiff, L., Rice, S. A., Dowdeswell, T., Yang, X. and McFadden, G. 1994 A poxvirus protein with a RING finger motif binds zinc and localizes in virus factories. J. Virol. 68:4186-4195.
• Upton. C., Stuart, D.T. and McFadden, G. 1993 Identification of a poxvirus gene encoding a uracil DNA glycosylase. PNAS 90:4518-4522.
• Upton C., Mossman, K. and McFadden, G. 1992 Encoding of a homolog of the IFN-gamma receptor by myxoma virus. Science 258:1369-1372.