Visualizing and Directing Dynamic DNA Nanostructure Assembly With Single-Molecule Resolution

Funding Details
Natural Sciences and Engineering Research Council of Canada
  • Grant type: Research Tools and Instruments - Category 1 (<$150,000)
  • Year: 2014/15
  • Total Funding: $150,000
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Project Summary

The use of DNA in nanotechnology has become increasingly widespread with far-reaching advantages: these natural nanoscale building blocks are self-assembling, are able to organize species such as drugs, nanoparticles, and other biomolecules, and can store and read information to target specific molecules. DNA nanotechnology promises to revolutionize a wide range of in vitro diagnostics and therapeutics in the coming decade due its robust, programmable, and native biological character. Traditional analysis methods limit DNA nanotechnology development because they cannot simultaneously enable dynamic and structural information to be obtained about DNA nanostructures. Typically synthesis is performed in a test tube and visualization is performed on a dry surface using an Atomic Force Microscope, removing DNA nanostructures from their native solution environment and disrupting their properties. This infrastructure project will create a novel directed-assembly imaging platform for analyzing, visualizing and optimizing DNA nanostructures in a solution environment, based upon emerging nanoscale imaging technology called "CLiC". As recently covered by Genome Web (August 2014) and PNAS Cover Commentary (October 2014), this pragmatic nanotechnology "CLiC"s DNA into an adjustable templated nanoscape chamber, yielding crisp images of structural dynamics over long time periods and opening the door to dynamic manipulation of assembled shapes. It can visualize and manipulate DNA nanostructure constituents while they assemble, providing a mechanistic understanding of their formation and allowing us to create new kinds of structures. It can elucidate the mechanisms underlying the release of cargo by and digestion of DNA nanostructures when they interact with other small molecules in solution. The proposed research brings together experts in DNA nanotechnology, single-molecule imaging, molecular dynamics and kinetics, and in vitro diagnostics (ranging from cancer biomarkers to genomics). It creates a unique, world-class nanoscience research station to be used by tens of interdisciplinary trainees.