Higher-Order RNA Structure and Function in the HIV-1 Genome

Univ Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Abstract

? DESCRIPTION (provided by applicant): The HIV/AIDS epidemic remains a major global public health challenge. Currently 35 million individuals are infected with HIV, and 3 million new infections occur each year. A key challenge in controlling HIV infection is the evolution of drug-resistant strains. New therapeutic strategies are essential to effectively trump viral evolution an eliminate HIV spread. Current retroviral therapies consist of drug cocktails targeting diverse protein-based functions; however, the viral genomic RNA constitutes an unexplored target for viral intervention. Viral replication depends not only on the genetic code contained in the primary sequence, but also on the functional roles of complex high-order RNA structures. If RNA structure is to be an effective therapeutic target, accurate, nucleotide-resolution models of higher-order structures in the RNA genome must be developed. The goal of this proposal is to identify functional motifs in the HIV-1 genomic RNA using cutting-edge computational and experimental approaches. Computational strategies will be developed to identify and characterize RNA-protein interactions essential for viral maturation and to model tertiary structure motifs throughout the entire 9,200 nucleotide HIV-1 genome. Ultimately, this research will lead to novel high-throughput structural modeling strategies for identification of novel therapeutic targets within HIV-1 that can be applied to any disease-related RNA. Through this training program, I will gain expertise in structural analysis techniques, next generation sequencing, bioinformatics, and virology. My long-term goal is to become a leader in RNA-based disease research, and this experience will be critical as I work toward this objective.