Grant: Discovery Grants Program - Individual

Nucleic acids are tremendously versatile molecules. Aside from their role in information storage and transfer, DNA and RNA play active roles as functional molecules. They can act as catalysts, participate in ligand binding and play a role as material for building nanoscale molecular devices. However, functional nucleic acids are often thought of as a black box. The fine details of how these types of molecules work is not known. Their structures, how they interact with other molecules, how they fold into an active molecule are poorly understood. Moreover, the design of new applications that use functional nucleic acids are hindered by our lack of knowledge of how these molecules work. Research in my laboratory aims to tackle this lack of understanding and learn how functional nucleic acid molecules perform their complex functions. As an additional benefit, as we better understand the details of how functional nucleic acids carry out their tasks, we will use this knowledge to engineer new applications and to design structures with new binding abilities. As a model system for discovering how functional nucleic acids work, my laboratory is focused on understanding how the cocaine-binding DNA aptamer operates. Specific projects detailed in this proposal include determining the structure of the cocaine-binding aptamer bound to its target ligand, cocaine. We will use a combination of nuclear magnetic resonance (NMR) and small angle X-ray scattering (SAXS) techniques to determine the three-dimensional structure of the free and ligand-bound aptamer. We will also study the binding of the cocaine aptamer to a range of ligands and in a range of conditions in order to understand how the aptamer binds its target and to discover new aptamer-ligand pairs. Another goal of my research is to use the cocaine aptamer to form chains that assemble upon ligand binding. Together, my proposed research will shed light into how a functional nucleic acid works and apply this knowledge into new applications.