Andrea V. Gamarnik

The Gamarnik lab is interested in understanding the mechanisms of dengue virus replication at the molecular level. Dengue virus is the single most significant arthropod-borne viral pathogen in humans. The geographical spread and incidence of dengue infections have increased dramatically in recent years, while neither vaccines nor specific antiviral drugs exist to control this virus. The work of the lab has focused on defining the mechanism of viral genome replication, combining biochemistry, molecular biology, and biophysics, together with classical and molecular virology. They have proposed the first model for dengue virus genome replication, which includes identification of the promotor for viral RNA dependent RNA polymerase activity at the 5' end of the genome and RNA cyclization by long range RNA-RNA interactions. They have shown that the viral genome is a dynamic molecule that changes conformations responding to alteration of the environment of the infected cell. In addition, they are investigating the mechanisms of genome encapsidation and uncoating, which are processes that include interactions between the viral capsid protein and the viral RNA. Because dengue virus cycles between mosquitoes and humans, the lab has more recently investigated host specific forces that shape viral RNA structures during host adaptation. The ultimate goal of the lab is to generate knowledge and new tools to rationally design antiviral strategies against dengue and other RNA viruses.