Carstens, Eric B - Queen's University - Department of Biomedical and Molecular Sciences

个人简介

BSc - University of Alberta; Molecular genetics, cell biology, electron microscopy MSc - University of Alberta; Biochemical studies on Adenovirus 5-infected cells. Supervisor - Dr. Ray G. Marusyk PhD - Université de Sherbrooke; Genetic and biochemical analysis of adenovirus. Supervisor - Dr. Joe Weber Post-doctoral Fellow - Institute for Genetics, Cologne, Germany. Biochemical analysis of adenovirus, molecular biology of baculovirus, with Dr. Walter Doerfler

研究领域

Viral DNA replication Biochemical characterization of viral genes essential for viral DNA replication Regulation of genes required for DNA replication and transcription Viral DNA replication, analysis of essential virus genes and their regulation. Members of the Baculoviridae, a unique family of eukaryotic of rod-shaped enveloped viruses with large circular double stranded DNA genomes, are unique because of their production of two different phenotypes of viruses during their infection cycle, and their extreme host specificity. Baculoviruses replicate only in invertebrates, and many isolates exhibit a very specific host range, infecting only one or a few insect genera. It is this strict species specificity which makes the study of baculoviruses so interesting. The objectives of baculovirus research have focused on: their use as biological pest control agents, their use as very efficient eukaryotic expression vectors (BEVs). important model viruses for studying the processes of gene regulation and particularly DNA replication in invertebrates. the potential use of baculoviruses as vectors in gene therapy. Thus, although they do not replicate in mammalian cells, baculoviruses can attach to and localize their genomes to the nucleus of these cells. Why do they not then replicate? Why do they only replicate in insects, with a very strict host specificity? What factors regulate this strict host range? The fundamental research in my laboratory is directed towards examining some of these concepts. Since genome replication is an early event in the virus replication cycle, understanding the temporal regulation of gene expression leading to the initiation of DNA replication and late gene expression will provide clues about host range specificity (for a review, see: Carstens, 2009). We have been using Baculovirus, particularly an isolate of the Alphabaculovirus type species virus Autographa californica nucleopolyhedrovirus as a model (for a review, see: Carstens, 2012). The process of insect killing by baculoviruses is largely due to viraemia and generalized infection of tissues throughout the insect, a process that takes many days to kill the host insect, during which time, crop or forest damage due to insect feeding continues. By understanding the mechanisms of viral replication and interaction with host cell regulation, the genes involved in viral pathogenesis will be identified and exploited in new generation viruses for insect pest control. In addition, genes critical to establishing virus host range and virulence are being studied in order to learn which genes can be manipulated safely in designing new biological pesticides. At the same time, our research is leading to a greater understanding of the mechanism of baculovirus DNA replication and the functional significance of viral genes during this process. These studies will enable us to understand the restriction of baculovirus replication in nonpermissive systems, including mammalian cells. Our research has been funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada

近期论文

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Eugene Koonin , Mya Breitbart , Mike Adams , Maria Benko , Rodney Brister , Eric B Carstens , Andrew Davison , Eric Delwart , Balazs Harrach , Roger Hull , Mart Krupovic , Jens Kuhn , Elliot Lewfkowitz , Max Nibert , Richard Orton , Marilyn Roossinck , Sead Sabanadzovic , Matthew Sullivan , Curtis Suttle , Robert Tesh , Rene van der Vlugt , Arvind Varsani , Murilo Zerbini , Andrew King , Alexander Gorbalenya (2016) Virus taxonomy in the age of metagenomics. Nature Reviews Microbiology 15:161-168 Downie, K. G. Adetola, and E. B. Carstens (2013) Characterization of protein-protein interaction domains within the baculovirus AcMNPV Late Expression Factor LEF-3. J. Gen Virol. 94: 2530-2535 Yu, M. and E. B. Carstens (2012) The CfMNPV LEF-3/P143 complex can complement DNA replication and budded virus production in an AcMNPV LEF-3/P143 double knockout bacmid. J. Gen. Virol. 93:383-388 Yu, M. and E. B. Carstens (2011) Characterization of an Autographa californica multiple nucleopolyhedrovirus mutant lacking the ac39 (p43) gene. Virus Research 155:300-306 Carstens, E. B. (2011) Baculoviruses. In: Fundamentals of Molecular Virology, 2nd Edition pp 302-311. Edited by N. Acheson. (John Wiley & Sons Canada Ltd.) Yu, M. and E. B. Carstens (2010) Identification of a Domain of the Baculovirus AcMNPV Single-Strand DNA Binding Protein LEF-3 Essential for Viral DNA Replication. J. Virol 84:6153-6162 Au, V., M. Yu, and E. B. Carstens. (2009) Characterization of a Baculovirus Nuclear Localization Signal Domain in the Late Expression Factor 3 Protein. Virology. 385:209-217 Carstens, E. B. (2009) AcMNPV as a Model for Baculovirus DNA replication. Virologica Sinica 24: 243-267 Carstens, E. B. and Y. Wu. (2007) No Single Homologous Repeat Region is Essential for the Baculovirus Autographa californica Nucleopolyhedrovirus Viral DNA Replication. J. Gen. Virol. 88:114-122. Carstens, E. B. (2007) Baculoviruses. In: Fundamentals of Molecular Virology pp 147-156. Edited by N. Acheson. (John Wiley & Sons Canada Ltd.) Wang, X., E. B. Carstens, and Q. Feng. (2006) Characterization of Choristoneura fumiferana genes of the sixth subunit of the origin recognition complex: CfORC6. J. Biochem. Mol. Biol. 39: 782-787. Chen, Z. and E. B. Carstens (2005) Identification of Domains in Autographa californica multiple nucleopolyhedrovirus LEF-3 Required for Nuclear Transport of P143. J. Virol. 79:10915-10922 de Jong, J., C. Dominy, A. Arif, H. Lauzon, E.B. Carstens and P. Krell. (2005) Analysis of the Choristoneura fumiferana nucleopolyhedrovirus Genome. J.Gen.Virol. 86: 929-943 Ito, E., D. Sahri, R. Knippers, and E. B. Carstens (2004) Baculovirus proteins IE-1, LEF-3, and P143 interact with DNA in vivo: a formaldehyde cross-linking study. Virology 329:328-336. Chen, T., D. Sahri and E. B. Carstens (2004) Characterization of the interaction between P143 and LEF-3 from two different baculovirus species: CfMNPV LEF-3 can complement AcMNPV LEF-3 in supporting DNA replication. J.Virol. 78:329-339. Carstens, E.B., J. J. Liu, and C. Dominy. (2002) Identification and Molecular Characterization of the Baculovirus CfMNPV Early Genes: ie-1, ie-2 and pe38. Virus Research 83:13-30. Carstens, E.B. (2002) Genus: Nucleopolyhedrovirus (Baculoviridae). In: The Springer Index of Viruses edited by C.A. Tidona and G. Darai. Lapointe, R., D.W. Back, Q. Ding and E.B. Carstens (2000) Identification and molecular characterization of the Choristoneura fumiferana multicapsid nucleopolyhedrovirus genomic region encoding the regulatory genes pkip, p47, lef-12 and gta. Virology 271:109-121 Wu,Y. G. Liu and E.B. Carstens (1999) Replication, integration and packaging of plasmid DNA following cotransfection with baculovirus viral DNA. J. Virol. 1999. 73:5473-5480. Liu, G. and E.B. Carstens. (1999) Site-directed mutagenesis of the AcMNPV p143 gene: effects on baculovirus DNA replication Virology 253:125-136. Wu, Y. and E.B. Carstens. (1998) A baculovirus single-stranded DNA binding protein LEF-3 mediates the nuclear localization of the putative helicase P143. Virology 247:32-40. Laufs, S. , A. Lu, K. Arrell and E.B. Carstens. (1997) Autographa californica nuclear polyhedrosis virus p143 gene product is a DNA binding protein. Virology 228:98-106. Liu, J. J., and E. B. Carstens (1996) Identification, molecular cloning and transcription analysis of the Choristoneura fumiferana Nuclear Polyhedrosis Virus spindle-like protein gene. Virology 223:396-400. Wu, Y, and E. B. Carstens (1996) Initiation of baculovirus DNA replication: early promoter regions can function as infection dependent replicating sequences in a plasmid based replication assay. J.Virol. 70: 6967-6972. Lu, A. , A. Craig , R. Casselman and E.B. Carstens. (1996) Nucleotide sequence, insertional mutagenesis and transcriptional mapping of a conserved region of the baculovirus Autographa californica nuclear polyhedrosis virus (map unit 64.8 to 66.9) Can. J. Micro. 42:1267-1273.