Department of Chemistry
University of Connecticut
Using enzymes to build, break and read hybrid DNA nanomaterials: from nanoscale self-assembly to intracellular gene regulation:
Biology has evolved the quintessential nanoscale assembly of nucleic acids, lipids, and proteins in the form of a virus. Viruses are built from self-assembled peptide subunits surrounding charged nucleic acids, packaged within a lipid-like envelope. Viral coat proteins are enzymatically degraded, in a location-specific manner, releasing contents into the surrounding environment. Our lab seeks to mimic not only the assembly, but the programmed disassembly, of biomolecule-based nanomaterials through a combination of chemical crosslinking strategies and enzymatic assembly steps. Using a hybrid DNA surfactant and a peptide-based self-assembly method, we have built a series of crosslinked micelle systems that break down in response to the presence of various stimuli, including pH and enzymes. The nanocapsule displays highly specific responses in the presence of closely related proteases and can be modified with inorganic nanoparticles for monitoring its stability using electron microscopy. Integrating natural biochemical ques into the assembly and degradation pathways of nanomaterials brings us one step closer to designing precision biomaterials, paving the road for greater accuracy in applications ranging from gene delivery to biosensing.
Jessica Rouge earned her BS in Biochemistry in 2006 from Boston College, where she conducted research in the laboratory of Shana Kelley. While there, she helped develop an aqueous route for synthesizing semiconductor quantum dots with tunable emission profiles using DNA building blocks as ligands. Next, Jessica earned a PhD in Chemistry in Bruce E. Eaton’s laboratory at the University of Colorado in 2012. While in Colorado, she learned of the incredible diversity of structures and functions that the biomolecule RNA possessed, along with the utility of in vitro selections for isolating highly specialized RNA structures known as aptamers. Although in vitro selections are traditionally used for identifying aptamers that target specific proteins and biomolecules, Jessica explored RNA’s potential to mediate the formation of inorganic nanoscale structures, much like an organism can guide the formation of bones and shells. After completing her PhD, Jessica began her postdoctoral studies in 2013 in the laboratory of Chad A. Mirkin at Northwestern University. There, she applied the skills she learned for interfacing RNA and inorganic materials for developing enzymatic assembly approaches useful for synthesizing RNA gold nanoparticle conjugates with the potential for intracellular gene regulation applications. Using this approach, she was able to target the knockdown of two separate genes with a single nanoparticle construct. In 2015, Jessica joined the faculty of the University of Connecticut as an Assistant Professor in the Department of Chemistry, where she combines the chemical diversity of nucleic acids with the synthesis of nanoscale materials in new ways to tailor the properties of hybrid nanomaterials for stabilizing and delivering nucleic acids. She was recently recognized with an NSF CAREER grant for her work designing hybrid nanomaterials with highly selective degradation properties, useful for both biological and catalysis applications.