Postdoctoral position available. Herpes Simplex Virus DNA Replication.
A postdoctoral research position is available with Dr. Sandra K. Weller
in the Department of Microbiology, University of Connecticut School of
Medicine, Farmington Connecticut. This research is funded by a 5-year
NIH grant to study DNA replication in Herpes Simplex Virus type 1.
Specifically we are in the process of carrying out structure-function
analyses of two viral helicases: UL9, a multifunctional protein of HSV-1
which exhibits origin specific DNA binding, dimer formation, helicase
and ATPase activities and UL5 a subunit of a heterotrimeric
helicase-primase composed of the products of the UL5, UL52, and UL8
genes. The helicase/primase exhibits ATPase, ss and ds DNA binding,
helicase and primase activities. Both UL9 and UL5 contain six sequence
motifs found in DNA and RNA helicases of superfamilies I and II. Motifs
I and II comprise an NTP binding site consensus sequence; however, the
role(s) of the other helicase motifs are unknown for any helicase.
Single amino acid substitutions created in each motif abolish the
ability of UL5 and UL9 to support viral DNA replication in vivo [Zhu,
L. and Weller, S.K. (1992) J. Virol. 66: 469; Martinez et al. (1992) J.
Virol. 66:6735]. Wild-type UL5 and several motif variant proteins have
been individually overexpressed and purified from a recombinant
baculovirus system (Graves-Woodward, K. L. and Weller, S. K. (1996) J.
Biol. Chem., 271:13629; Graves-Woodward K.L. and Weller, S.K. (1996) J.
Biol. Chem. in preparation). Future projects include further
structure-function analysis of both UL9 and the helicase/primase. For
instance, UL52 which specifies the primase of the heterotrimeric complex
contains a zinc finger domain, and we wish to determine the role of this
domain in primase activity, ss and ds DNA binding and helicase activity
of the complex. Other lines of investigation in the laboratory involve
analysis of the structure of replicating viral DNA, intranuclear
localization of viral replication proteins and protein-protein
interactions with viral and cellular proteins. The successful applicant
will have experience with protein biochemistry. Preference will be
given to applicants who also have experience with molecular biology
and/or virology, but this is not necessary. The starting dates and
salaries are flexible; the latter depends on experience. Benefits are
provided. Interested applicants should fax or e-mail a CV including
names and contact addresses of 3 referees to: Dr. Sandra K. Weller,
Professor of Microbiology, MC3205, University of Connecticut Health
Center, 263 Farmington Ave., Farmington, CT 06030. Fax: (860) 679-1239.
Weller at panda.uchc.edu.