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Professor, Associate Dean for Graduate Health Science Studies and Vice Chancellor of The University of Toledo
2011 ASV meeting July 16-20, 2011
Dr. Sawicki studies the mechanisms used by alphaviruses and a related group of animal and plant RNA viruses to control the
synthesis of viral RNA. These viruses are members of the Sindbis superfamily and share extensive homology in the sequences
of their polymerase proteins with the animal alphaviruses, Sindbis virus and Semliki Forest virus. Alphaviruses are of general
interest because they produce disease in a variety of animals, including humans, and because they replicate in invertebrates
as well as vertebrates. Her studies focus on the synthesis of the viral template or minus-strand RNA that is needed to amplify
the viral information, to form progeny genomes, and to allow the virus to take over the synthetic machinery of the cell. In
nature, a balance exists between alphaviruses and their invertebrate hosts such that there is limited replication of the virus
with survival of the host. This phenomenon of viral persistence has been studied using a collection of temperature sensitive
mutants that fail to cause the synthesis of viral RNA at nonpermissive temperature, in particular mutants that are defective
specifically in minus-strand RNA synthesis. The mechanisms responsible for regulating the synthesis of minus-strand RNA and
for determining the maximal rate of viral RNA synthesis are being studied. Mutations responsible for defects in viral RNA
synthesis are being mapped to particular viral proteins by constructing recombinant mutant genomes in infectious cDNA clones
of Sindbis virus and by sequencing those regions expressing functional defects. Other studies use in vitro RNA synthesizing
systems to elucidate the nature of the viral replication complexes and the mechanism of alphavirus RNA synthesis. The essential
role of polyprotein forms of the viral polymerase proteins in minus strand synthesis but not in genome or mRNA synthesis,
proposed by this lab, is being pursued using an in vitro reconstitution system to probe functions necessary for promoter recognition,
elongation, temporal regulation of minus strand synthesis and internal initiation by the viral transcriptase to form a subgenomic
Dé, I., Fata, C.L., Sawicki, S.G., and Sawicki, D.L. (2003) Functional analysis of nsP3 phosphoprotein mutants. J. Virol. 77(24):13106-16.
Sawicki, D.L., Silverman, R.H., Williams, B.R., and Sawicki, S.G. (2003) Alphavirus minus-strand synthesis and persistence in mouse embryo fibroblasts derived from mice lacking RNase L and protein kinase R. J. Virol. 77: 1801-1811.
Fata, C.L., Sawicki, S.G., and Sawicki, D.L. (2002) Modification of Asn374 of nsP1 suppresses a Sindbis virus nsP4 minus-strand polymerase mutant. J. Virol. 76: 8641-8649.
Fata, C.L., Sawicki, S.G., and Sawicki, D.L. (2002) Alphavirus minus-strand RNA synthesis: identification of a role for Arg183 of the nsP4 polymerase. J. Virol. 76: 8632-8640.
Sawicki, D., Wang, T., and Sawicki S. (2001) The RNA structures engaged in replication and transcription of the A59 strain of mouse hepatitis virus. J. Gen. Virol. 82: 385-396.
Sawicki, S.G. and Sawicki, D.L. (1998) A New Model for Coronavirus Transcription. Advances in Experimental Medicine, 440: 215-220.
Sawicki, D.L and Sawicki, S.G. (1998) Role of the nonstructural polyproteins in alphavirus RNA synthesis. Advances in Experimental Medicine, 440: 187-198.