Medical Microbiology and Immunology : Dorothea L. Sawicki, Ph.D.

Professor and Associate Dean, College of Graduate Studies
The study of mechanisms used by alphaviruses and RNA viruses to control the synthesis of viral RNA
E-mail Address: dorothea.sawicki@utoledo.edu
Office Phone Number: (419) 383-4337

Selected 2009 Wells College Alumnae Award

Secretary-Treasurer
American Society of Virology
University of Toledo, Health Science Campus
ASV office Phone number (419) 383-5173
info: 2010 ASV meeting, Montana State University, Bozeman 

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 mRNA.

Dr. Sawicki received her Ph.D. in 1972 at Columbia University, New York. She did postdoctoral work at the Sloan-Kettering Cancer Institute, New York, with Dr. Peter Gomatos (retroviruses and alphaviruses). She is a member of the editoral board of the Journal of Virology.

Current Grants
NIH - Alphavirus minus strand RNA synthesis and Rnase L
ASV - Secretarial Grant Account

Representative publications:

Mai, J., Sawicki, S., Sawicki, D.  (2009)  Fate of minus strand templates and replication complexes produced by a P23-cleavage defective mutant of Sindbis virus.  J Virol. June 10. [Epub ahead of print].
 
Lulla, V., Sawicki, D.L., Sawicki, S., Lulla, A., Merits, A., Ahola, T.  (2008)  Molecular defects caused by temperature-sensitive mutations in Semliki Forest virus nsP1.  J. Virol. 82:9236-9244.  

Gorchakov, R., Frolova, E., Sawicki, S., Atasheva, S., Sawicki, D., and Frolov, I.  (2008)  A new role of ns polyprotein cleavage in Sindbis virus replication.  J. Virol. 82:6218-6231.

Sawicki, S.G., Sawicki, D.L., Siddell, S.G.  (2007)  A contemporary view of coronavirus transcription.  J Virol. 81:20-29.  

Sawicki, D.L., Perri, S., Polo, J.M., Sawicki, S.G. (2006) Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells.  J. Virol. Jan;80(1):360-376.

Mahboubi, K., Witman-Jones, T., Adamus, J.E., Letsinger, J.T., Whitehouse, D., Moorman, A.R., Sawicki, D., Bergenham, N., Ross, S.A. (2006) Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74.  Biochem Biophys Res Commun.  Feb 10; 340(2): 482-490.

Sawicki, S.G., Sawicki, D.L., Younker, D., Meyer, Y., Thiel, V., Stokes, H., and Siddell, S.G.  (2005) Functional and genetic analysis of coronavirus replicase-transcriptase proteins. PLoS Pathog.1(4):e39. Epub Dec 9. Review.

Sawicki, D.L., Perri, S., Polo, J.M., and Sawicki, S.G. (2006)  Role for nsP2 proteins in the cessation of alphavirus minus strand synthesis by host cells. J. Virol. 80(1):360-371.

Sawicki, D.L. (2005) Coronavirus transcription: a perspective. Curr. Top. Microbiol. Immunol. 287:31-55.

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.