Grant: Canada Research Chairs

RNA vaccines became a household name during the global pandemic. These powerful tools to fight COVID-19 were made possible due to the introduction of modifications that enhance RNA stability in cells. Indeed, although nucleic acids (DNA and RNA) are the most basic molecules of life, being required to store and transmit genetic information, their nucleotide building blocks are commonly chemically modified to enhance their structural stability and function. In nature, nucleic acids are modified to control gene expression and build properly functioning proteins. Synthetic modified nucleic acids have also been designed for medicinal uses such as therapeutics, antimicrobials or tissue engineering, as well as for nanomaterials to build nanowires or nanomachines. Unfortunately, the lack of knowledge regarding how modifications change the structure and function of nucleic acids raises questions such as why nature introduces modifications and how modifications can be used to their full potential in valued applications. Dr. Wetmore will use computer modeling to find answers by gaining a fundamental understanding of the chemistry of modified nucleic acids. As a CRC, Wetmore will use sophisticated computational techniques and complex models to explore exciting new developments related to natural and synthetic nucleic acid modifications, and enzymes that process modified nucleic acids. Calculations are critical tools for solving these problems, being powerful predictors of experimental outcomes and providing information necessary to guide future experimental studies. Wetmore’s research will address the lack of data for the effects of transfer RNA modifications on protein synthesis. This is an important first step toward understanding human diseases (cancer, diabetes, neurodegeneration) associated with modification errors. She will also uncover the fundamental chemistry of modifications synthesized for use in nucleic-acid-based aptamer and siRNA medicines. By understanding why certain chemical substitution types and patterns enhance drug function, her work will help unlock the ability to treat many diseases. Finally, Wetmore will clarify how enzymes in nature cleave strong bonds that hold nucleic acids together. This insight will guide future work geared towards designing new drugs for treating diseases linked to mutations in human enzymes and developing ways to process modified nucleic acids as tools in biochemistry or to synthesize new biomaterials for nanotechnology.