Combinatorial DNA nanoparticle libraries for structural biology and materials research
Abstract
Nanoscale structured DNA assemblies have transformative potential for diverse applications in biomolecular and materials science. We have developed the computational tool DAEDALUS (http://daedalus-dna-origami.org/) to facilitate the rapid design of DNA nanostructures based on arbitrary 3D geometries. Recently, we have expanded the scope of our top-down design algorithms to 2D geometries (PERDIX) and highly rigid 3D architectures (TALOS). This fully automated computational platform for DNA nanostructure design complements our current experimental workflow to enable the synthesis of complex DNA origami nanostructures. Application of this DNA nanostructure design and synthesis pipeline towards structural RNA biology or the assembly of hierarchical DNA superstructures for materials research requires the functionalization of DNA origami objects with reactive groups or single-stranded bait sequences. Furthermore, these applications depend on the high-throughput generation of DNA nanostructure libraries with varying geometry, size and functionalization patterns. While our current synthesis workflow leveraging in-house DNA synthesis, can generate large numbers of the required oligonucleotide sequences at the required scale, the manual liquid handling of these libraries becomes exceedingly challenging. Hence, integrating an automated liquid handling system into our experimental pipeline will enable advanced capabilities to synthesize functional DNA origami-based materials for diverse applications pursued in our lab and by collaborators. Acoustics-based robotic systems are the only instruments that combine throughput and versatility with the required precision required for DNA nanotechnology. Currently, no modern liquid handling system is accessible to us in any facility at MIT that provide all of these capabilities. For this reason, we seek to acquire the next-generation acoustics-based Echo 555 with Omix calibration manufactured by LabCyte. This instrument would complement our experimental DNA origami research objectives that are currently funded by the ONR, DoE, NIH, and NSF. We will offer our automated liquid handling capabilities as an enabling facility for the MIT Biological Engineering Department Teaching Laboratory to facilitate practical learning by undergraduate and graduate students interested in nucleic acid nanotechnology and combinatorial library generation for synthetic biology. APPROVED FOR PUBLIC RELEASE..
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 23, 2019
- Source ID
- N000141912344
Entities
People
- Mark Bathe
Organizations
- Massachusetts Institute of Technology
- Office of Naval Research
- United States Navy