Laboratory of Molecular Microbiology

Malcolm A. Martin, M.D., Chief

When it was established in 1981, the Laboratory of Molecular Microbiology (LMM) investigated the structure, function, and regulation of a diverse group of microorganisms including RNA and DNA viruses, aerobic and anaerobic bacteria, and mycoplasmas. Currently, the main focus of LMM scientists is murine (MuLV) and primate retroviruses (HIV, SIV, and HTLV) with the principal area of research activity involving human immunodeficiency virus (HIV-1). Fundamental investigations of viral gene regulation, protein structure and function, and particle assembly are integrated with studies of the determinants of immunologic protection against HIV and viral pathogenesis.

Major Areas of Research

• Studies of the synthesis, processing, and assembly of retroviral encoded proteins into progeny virions
• Exploration of the structure and function relationship of retroviral accessory proteins synthesized during productive and chronic viral infections
• Understanding the regulation of retroviral gene activity and how viral encoded proteins dysregulate normal cellular processes
• Development of animal models for investigations of viral pathogenesis, the identification of potentially useful antiviral agents, and the development of protective vaccines

Major Accomplishments

• LMM investigators constructed one of the most widely used infectious molecular clones (pNL4-3) of HIV-1.
• LMM researchers developed SIV/SHIV non-human primate models to study primate lentivirus pathogenesis and vaccine efficacy.
• LMM researchers defined the mechanisms by which HIV tat and rev function.
• LMM investigators discovered the critical amino acids in HIV-1 p6 conferring "late domain" Gag activity.
• LMM researchers identified two novel HIV genes (vpu and vif) that are expressed in vivo. Vpu was subsequently shown at LMM to regulate the release of virus particles from cells and induce CD4 degradation. The Vif protein was shown at LMM to be essential for virion infectivity.
• LMM scientists have determined the phylogenetic relationships among nonhuman primate lentiviruses.
• LMM investigators cloned and characterized unique cellular genes that may augment viral trans-regulators.
• LMM scientists constructed DNA panels of somatic cell hybrids and interspecies backcross progeny for genetic dissections of the mouse genome.

Future Directions

• Apply molecular and biological techniques to study the structure, function, and regulation of viral and eukaryotic genes.
• Characterize genetic elements (both chromosomal and episomal) affecting the interaction of microorganisms and the cells they infect.

Office of the Chief

Malcolm A. Martin, M.D.

Molecular Biology CORE

Alicia Buckler-White, Ph.D.

Viral Pathogenesis and Vaccine Section

Malcolm A. Martin, M.D.
Vanessa M. Hirsch, D.V.M., D.Sc.
Fadila Bouamr, Ph.D.

Biophysical Virology Section

Jonathan Silver, M.D.

Molecular Virology Section

Kuan-Teh Jeang, M.D., Ph.D.

Viral Biochemistry Section

Klaus Strebel, Ph.D.

Viral Biology Section

Christine A. Kozak, Ph.D.

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