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DoD MURI: Translating Biochemical Pathways to Non-Cellular Environments

In this Multidisciplinary University Research Initiative (MURI), established in 2012, we are seeking apply the organizational power of DNA nanotechnology to the challenge of translating biochemical pathways to non-cellular environments. The pathways that convert mass and energy in all living organisms are dependent on the precise arrangement of participating elements, and the ability to exert control over these pathways outside the cell could make enzyme catalyzed production of molecular species and conversion of various forms of energy more efficient. Our multidisciplinary team consists of six leading researchers from four top-rated universities, with expertise in DNA nanotechnology, computational biology and biophysics, protein chemistry and bioconjugation, photo-biochemistry, porous material synthesis and single molecule biophysics. This research is being supported by the Department of Defense MURI program through the Army Research Office (ARO).


Our Mission

MURI Mission

 

Develop bottom-up self-assembly approaches to translate biochemical pathways to non-cellular environments


Our Team

MURI team

 

11 Postdocs, 10 Graduate students

A multidisciplinary team with expertise in DNA nanotechnology, computational biology and biophysics, protein chemistry and bioconjugation, photo-biochemistry, material chemistry and single molecule biophysics to design, model, construct and characterize a series of DNA templated biochemical pathways.

Principal Investigator
Hao Yan, ASU
hao.yan@asu.edu; 480-727-8570
Biodesign Institute, Arizona State University

Co-PIs and Subcontract
Neal Woodbury, ASU
Don Seo, ASU
Mark Bathe, MIT
William Shih, Harvard
Nils Walter, U. of Michigan
Jinglin Fu, Rutgers U.

Program Directors
Dr. Stephanie McElhinny & Dr. John Prater
Army Research Office


Major Meeting

MURI Kickoff Meeting
Arizona State University, Tempe, AZ, USA
July 20, 2012

MURI Year 1 – 6 month review
Arizona State University, Tempe, AZ, USA
February 27, 2013

MURI Year 1 – annual review
Hilton Arlington, Arlington, VA, USA
October 28, 2013

MURI phase I review
Arlington, VA, USA
July 29, 2014

MURI Year 3 – annual review
January 28, 2015

Muri Team skype


Major Review Results

"The PIs have clearly been working hard over the past year and they have made excellent progress."

"Overall, substantive progress has been made in the first year, especially with the design and characterization of the DNA nanostructure-based elements for assessing multi-enzyme performance and for the assembly of the light harvesting complexes."

"The experimental work is all nicely coordinated with work on single molecule modeling and characterization. The single molecule analysis is a considerable strength of the MURI team."

"The integration of complementary experimental and theoretical tasks in the MURI is a significant strength of the program."


Major Accomplishments

Mass Conversion Pathways – Multi-Enzyme Systems

  • Designed and constructed multi-dimensional DNA scaffolds for enzyme organization  -- DNA nanocages, channels and 2D & 3D lattices. (Yan & Shih labs)
  • Designed and constructed substrate-channeled multi-enzyme complex – a swinging arm system, DNA scaffolded liposome. (Yan, Woodbury & Walter    labs)
  • Investigated the activity enhancement property of compartmentalized enzymes in DNA nanocages with both bulk and single molecule measurements. (Yan, Walter and Shih labs)
  • Used super-resolution fluorescent microscopy to characterize the single molecule kinetics of the DNA scaffolded molecular complex and enzyme complexes and integrated with theoretical modeling to improve the experimental designs. (Walter, Yan and Bathe labs)
  • Developed novel materials as optimal electrode surfaces for the multi-enzyme systems –transparent and conducting porous material and functionalized graphene. Investigated molecular diffusion through the porous materials using single molecule measurements. (Seo, Yan and Walter labs)

Energy Conversion Pathways – Photosynthetic systems

  • Engineered fluorescent dye conjugated reaction center to enhance and control the absorption cross-section of photosynthetic reaction center. (Woodbury & Yan labs)
  • Designed and constructed a DNA scaffold for stepwise energy transfer to reaction center proteins. (Yan & Woodbury labs)
  • Implemented calculation of light energy transfer in DNA nanostructures conjugated with dye molecules. (Bathe & Yan labs)
  • Implemented Brownian Dynamics calculations in order to model effects of time-dependent DNA nanostructure motions on light-harvesting efficiency. (Bathe lab)
  • Developed protocols to assemble light harvesting and reaction center proteins onto 2D DNA scaffolds (Woodbury & Yan labs).
  • Tested the incorporation of reaction center proteins into transparent and conducting porous materials (Woodbury & Seo labs).

Publications

  1. A. Johnson-Buck, J. Nangreave, D. Kim, M. Bathe, H. Yan, N. G. Walter, Super-Resolution Fingerprinting Detects Chemical Reactions and Idiosyncrasies of Single DNA Pegboards, Nano Letters, 13, 728-733 (2013).
  2. M. Liu, J. Fu, C. Hejesen, Y. Yang, N. W. Woodbury, K. Gothelf, Y. Liu, H. Yan. A DNA Tweezer-actuated Enzyme Nanoreactor, Nature Communication 4, 2127 (2013).
  3. A. Johnson-Buck, J. Nangreave, S. Jiang, H. Yan, N. G. Walter, Multifactorial Modulation of Binding and Dissociation Kinetics on Two-Dimensional DNA Nanostructures, Nano Letters, 13, 2754–2759, (2013).
  4. Pan, K., Boulais, E., Yang, L., Bathe, M. Structure-based model for light-harvesting properties of nucleic acid nanostructures. Nucleic Acids Research, 42, 2159-2170 (2014).
  5. Perrault SD, Shih WM. Virus-inspired membrane encapsulation of DNA nanostructures to achieve in vivo stability. ACS Nano 8, 5132–5140, (2014).
  6. Johnson-Buck, A.; Jiang, S.; Yan, H.; Walter, N.G. DNA–Cholesterol Barges as Programmable Membrane-Exploring Agents, ACS Nano, 2014, 8, 5641-5649.
  7. J. Fu, Y. Yang, A. Johnson-Buck, M. Liu, Y. Liu, N. G. Walter, N. Woodbury, H. Yan.  Multi-enzyme complexes on DNA scaffolds capable of substrate channeling with an artificial swinging arm, Nature Nanotechnology, doi: 10.1038/nnano.2014.100, (2014).
  8. K.-W. Jeon, D.-K. Seo Concomitant Thionation and Reduction of Graphene Oxide Through Solid/Gas Metathetical Sulfidation Reactions at High Temperatures, Phosphorus, Sulfur Silicon Relat. Elem. 189, 721-737 (2014).
  9. P. Dutta, S. Lin, A. Loskutov, S. Levenberg, R. Saer, T. Beatty, Y. Liu, H. Yan, N. Woodbury, An Engineered System to Enhance and Control the Absorption Cross-section of Photosynthetic Reaction Center, J. Am. Chem. Soc. 136, 4599–4604 (2014).
  10. P. K. Dutta, S. Levenberg, A. Loskutov, D. Jun, R. Saer, T. Beatty, S. Lin, Y. Liu, N. W. Woodbury, H. Yan, A DNA-Directed Light-Harvesting/Reaction Center System, 136, 16618-16625 (2014).
  11. Das, B.; Reanude, A; Volosin, A.; Lei, Y.; Seo, D.-K. Nanoporous Delafossite CuAlO2 from    Inorganic/Polymer Double Gels: A Desirable High-Surface-Area p-Type Transparent Electrode Materials“ Inorganic Chemistry (2015) doi:10.1021/ic5023906.

Submitted:

  1. Jeon, K.-W.; Seo, D.-K. “Direct Thionation on Graphene Oxides with Phosphorus Decasulfide under Solvothermal Condition” Submitted.
  2. Z. Zhao, S. Dhakal, J. Fu, A. Andreoni, Y. Liu, N. G. Walter, H. Yan, “Nano-caged Enzymes with Enhanced Activity and Stability” Submitted.
  3. S. Dhakal, M. Adendorff, H. Yan, M. Bathe, N. Walter et al., “Rational design of DNA-actuated enzyme nanoreactors guided by single molecule analysis" Submitted.

Manuscripts in Preparation:

  1. Z. Ge, M. Liu, A. Andreoni, J. Fu, Y. Liu, H. Yan, Orientation Control of cytochrome c in DNA Nanostructures and Its Electron Transfer to Gold Electrode, in preparation.
  2. Min J, Wickham S, et al. O-Bricks: Cylindrical NanoPegboards Assembled from DNA, In preparation.
  3. Jeon, K.-W.; Seo, D.-K. “Direct Fabrication of Langmuir-Blodgett Films of Reduced Graphene Oxides via Thio Functionalization“, In preparation.
  4. Volosin, A.; Seo, D.-K. “Fabrication of Aerogel-Like Continuous Coatings of Antimony- Doped Tin Oxide via Nanoporous Carbon Template”, In preparation.
  5. Sharifi, R., Pan., K., Adendorff, M., Hallatschek, O., Bathe, K.J., Bathe, M. Finite element framework for long time-scale Brownian Dynamics of nucleic acid assemblies. In preparation.

Manuscripts in Preparation:

  1. Boulais, E., Sawaya, N., Aspuru-Guzik, A., Bathe, M. Computational framework for in silico analysis of excitonic properties of DNA-dye assemblies. In preparation.
  2. A. Johnson-Buck, Y. Yang, J. Li, H. Yan, Nils G. Walter, Rapid Unbiased Transport by a DNA Walker Utilizing Toehold Exchange, in preparation.

Patents

  1. D.-K. Seo, K.-W. Jeon, WO/2013/123308 (PCT/US2013/026314) Multifunctional   Materials and Composites (Publication Date: Aug. 22, 2013).
  2. Provisional Patent filed: “Self-assembly of Nucleic Acid” on DNA brick technology (Inventors: Y.  Ke, L. Ong, W. Shih, P. Yin)

Spinoff Company: Leccel LLC. (Founder: D.-K. Seo)