The laboratory of Dr. Stuart Le Grice periodically has postdoctoral openings available to study the biochemistry and molecular biology of reverse transcription and viral entry. Recent evidence with retroviral (HIV, FIV, EIAV) and retrotransposon (Ty1, Ty3) polymerases indicates that initiation of (–) strand DNA synthesis is mediated by long-range, intermolecular contacts between the tRNA primer and its cognate lentiviral genome. Sequence divergence between the (+) strand and polypurine tract primers is also a feature of the retrotransposons Ty1 and Ty3. The goal of the research program is to elucidate these mechanisms with respect to both the protein and nucleic acid components of the initiation complexes. Specific areas under investigation include:
- Application
of Bioconjugate Strategies to Monitor the Transition from
Initiation to Elongation of (–) Strand DNA Synthesis
Attachment of chemical proteases to viral RNA substrate
and specifically end-labeled recombinant enzymes will
be exploited to follow conformational changes in the replication
machinery. Initiation of reverse transcription in the
S. cerevisiae retrotransposon Ty3 exploits a bipartite
PBS comprising RNA sequences derived from the 5' and 3'
termini of the retrotransposon genome. Recombinant Ty3
RT and novel bioconjugate strategies will be implemented
to study this complex. [Click here
for additional information about this research area.]
- Evaluation of Protein/Nucleic Acid Complexes by Mass Spectrometry
Protein footprinting will be used to follow conformational
changes in HIV, FIV, and EIAV RT subunits during initiation
of (–) and (+) strand DNA synthesis. This project will
exploit variants of lentiviral enzymes that fail to catalyze
these events.
To apply for either of these fellowships, please submit a cover letter, CV including bibliography, and contact information
for three references to Stuart F.J. Le Grice, Ph.D., Resistance Mechanisms Laboratory, RT Biochemistry Section, HIV Drug Resistance Program, National
Cancer Institute, Building 525, Frederick, MD 21702-1201. Tel: (301) 846-5256. Fax: (301) 846-6013. E-mail: slegrice@ncifcrf.gov.
Note for Foreign Scientists: Applicants should be aware that the recruitment process is lengthy and the applicant's present visa status can affect the process; for additional information, please visit the web site of the Fogarty International Center.
