Overview of Our Research
Study of retroviruses has led to major advances in fundamental biology including the description of the first viruses that cause tumors (1, 2) and the discovery of oncogenes (3). Description of reverse transcription (4, 5), the process by which retroviruses make cDNA from the viral RNA genome, extended understanding of genetic information transfer in a manner consistent with the Central Dogma of Molecular Biology (6) (see draft with drawing by Francis Crick, below), and created new possibilities for understanding the Origin of Life (7). In this spirit, we investigate mechanisms of HIV-1 transmission, replication, pathogenesis, and immunity, with the goal of advancing understanding of the basic workings of the cell.
The simplicity of the HIV-1 genome renders the virus dependent upon host cell machinery at each step in the virus life cycle. Pathology associated with HIV-1 infection necessarily results from a finite set of interactions among cellular factors and the nine total HIV-1 genes (see top section of figure above). By developing and applying genetic and biochemical screens we attempt to identify cellular factors of functional relevance to the virus and, more generally, to cellular physiology. In effect, we exploit HIV-1, using the virus to elucidate mechanisms of cell cycle progression and cytokinesis, transcriptional regulation, genetic recombination, pluripotency, signal transduction, and cytokine expression, as well as protein folding and antigen presentation.
Our research is basic in nature but by shedding light on mechanisms of HIV-1 replication and immune system evasion we hope to contribute to the development of therapeutics and vaccines that target this virus, as well as seemingly unrelated diseases such as cancer, asthma, and diabetes.
References:
1. Ellerman C, Bang O. 1908. Experimentelle Leukämie bei Hühnern. Zentr Bakteriol 46:595.
2. Rous P. 1911. A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13:397–411.
3. Stehelin D, Varmus HE, Bishop JM, Vogt PK. 1976. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170–173.
4. Temin HM, Mizutani S. 1970. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–1213.
5. Baltimore D. 1970. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226:1209–1211.
6. Crick F. 1970. Central dogma of molecular biology. Nature 227:561–563.
7. Gilbert W. 1986. Origin of life: The RNA world. Nature 319:618–618.
