Expanding the function and utility of nucleic acids

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Better known as the blueprint of all living organisms on earth and the foundation of modern biology, nucleic acids - both DNA and RNA - have been repeatedly shown to have other talents, which include the ability to function as catalysts (enzymes) and molecular detectives (receptors). A growing number of natural and man-made nucleic acids with intriguing catalytic or binding functions have been discovered, and their existence has inspired scientists from many disciplines to investigate their fundamental properties and use them to develop new concepts as well as diverse applications in chemistry, biotechnology, materials science, nanotechnology and medicine. My group has been studying three different classes of functional nucleic acids: DNAzymes, aptamers and riboswitches. A DNAzyme is a man-made DNA-based “molecular engine” that can speed up a chemical transformation. An aptamer is a man-made DNA or RNA “molecular detective” that can pinpoint a specific molecular target (like a biomarker of a disease) from a complex molecular mixture. A riboswitch is a cellular RNA-based “molecular switch” that tells a cell whether it needs to synthesize a specific molecule for supporting its living activities. Therefore, DNAzymes, aptamers and riboswitches are important molecules to study for fundamental knowledge acquisition as well as for practical applications. We will pursue four specific aims within this proposed NSERC Discovery Grant program. First, we will establish a versatile, ultra-sensitive biosensing platform that integrates aptamers as stimuli-responsive molecular switches with a powerful signal amplification technique. Second, we will develop DNAzymes that catalyze an important new chemical reaction, RNA methylation, as an effort to continue the expansion of the catalytic repertoire of DNA. Third, we will develop riboswitch-based biosensors that make it easy to examine molecular functions in living cells. Last but not least, we will engineer intricate DNA-based nanomachines that incorporate DNA aptamers and DNAzymes as essential functional components. It is expected that through these studies, we will generate new knowledge about DNAzymes, aptamers and riboswitches, which in turn will lead to the development of new molecular systems that scientists can utilize to answer fundamental questions about biological catalysis and molecular recognition. The proposed work will also create new approaches towards developing bioanalytical applications for safer food, a better environment and more effective diagnostic methods for Canadians and people around the world. Furthermore, this grant will allow my laboratory to develop talented, next-generation scientists, which will help ensure Canada’s future competitiveness in science, technology, and knowledge-driven global economy.