STRUCTURAL DYNAMICS OF TWO FRAGMENT SEQUENCES FROM BACTERIA AND VIRAL RNAs

Abstract

This research investigates the many roles and applications of ribonucleic acids (RNAs). Nobel Prize recognized discoveries and recent advances in biomedicine underscores RNA’s emerging significance as a key molecule for pharmaceutical innovation and vaccine development. This thesis focuses on the structural dynamics of RNA molecules ultimately relevant to major global health concerns of antibiotic resistance and Human Immunodeficiency Virus (HIV) infection. In addressing antibiotic resistance, the conformational flexibility of prokaryotic rRNA sequence targeted by antimicrobials and those derived from an off-target eukaryotic rRNA sequence was characterized using Nuclear Magnetic Resonance (NMR) spectroscopy. NMR can characterize both local and global RNA dynamics across multiple timescales. These results may contribute to improving the efficacy of RNA-targeted antimicrobials. Similarly, the conformational flexibility of an RNA sequence specific to HIV type 2 was examined using NMR spectroscopy to gain deeper insight into its dynamic properties. Characterizing the structural dynamics of these HIV type 2 RNA may inform strategies to enhance the efficacy of RNA-targeting therapeutics and expand the existing body of knowledge regarding their cellular function. Such insights could ultimately facilitate the development of drugs designed to recognize and bind biologically relevant HIV type 2 RNA conformations. Finally, this work integrates an educational component that details pedagogical strategies for teaching advanced RNA-related topics, namely solution nuclear magnetic resonance (NMR) spectroscopy dynamics experiments and NMR relaxation data analysis to undergraduate students.