Chemistry and Biochemistry
Area of Doctoral Study: Biochemistry
Undergraduate Institute: University of Maryland, College Park
Research Advisor: Michael F. Summers, Ph.D.
Description of Research
The research focus in my lab is the late phase of the HIV-1 life cycle, specifically, viral genome recognition and assembly. The macromolecular interactions involved in the assembly of retroviruses are still poorly understood. We study several animal models including the Moloney Murine Leukemia Virus (MoMuLV). Gag is the major viral structural protein. It is sufficient for efficient assembly and release of virus like particles. Genomic RNA also plays a structural role in retrovirus particles during assembly by acting as “scaffolding” for assembling Gag polyproteins as evidenced in several retroviruses including HIV-1. We recently discovered that a dimer form of a large fragment of the MoMuLV 5’ UTR containing all necessary residues for RNA packaging bound ~12 NC molecules with high affinity Kd=17+/-7 nm) while the monomer only bound ~1-2 NC molecules [Miyazaki, Y., et al. (2010) JMB 396, 141-152]. This study suggests that a Gag12:RNA complex could serve to nucleate assembly, in which RNA is the scaffolding structure for Gag binding. These results have propelled us in to the next phase in which we will further study the MoMuLV 5’ UTR through structural and biophysical studies to determine if MoMuLV and HIV-1 share a similar nucleation event requiring the participation of a small number of Gag molecules bound to a dimeric RNA molecule.