Army-ECASE: Develop Synthetic Compartments For Enhanced And Regulated Biochemical Reactions
Abstract
Statement of objectives: The proposed research will apply the organization power of structural DNA nanotechnology to the development of bio-mimetic compartments with controlled spatial confinements, regulated transmembrane diffusions and feedback functions. The specific aims are: (1) Development of synthetic compartments with controlled geometry and confined local environments. (2) Development of DNA-scaffolded transmembrane nanopores with controlled open and close. (3) Chaperone-like encapsulation of biochemistry pathways with enhanced catalysis and improved stability. (4) Feedback regulation of a compartmentalized biochemical pathway. Methods to be employed: DNA nanostructures with specific geometries will be designed and used as the assembly scaffolds. Self-assembled DNA nanoscaffolds will be used to confine lipid vesicles with rationally programmed shapes and sizes. Biochemical reactions will be encapsulated by the engineered compartment with activities regulated by transmembrane nanopores or proximity assembly circuits. The structural assembly and conformational switch will be characterized at single-molecule level, including atomic force microscope, transmission electron microscope and single-molecule fluorescence microscopy. Enzyme kinetics measurements will be employed to evaluate the functional performance of nanoreactors. Significance: Our proposed strategy of synthetic compartments involves the development and integration of several key bio-mimetic elements, including controlled spatial confinements, transmembrane nanopores, feedback regulation and proximity assembly. The proposed research will establish multidisciplinary approaches that combines DNA nanotechnology, bioconjugation, enzymology, vesicle assembly and single-molecule characterization. The proposed research promises to deliver several technical breakthroughs that will enable the engineering of regulatory biomolecular complexes on the nanoscale. Synthetic and bio-mimetic reactors have great potential for broad applications ranging from chemical synthesis, functional biomaterials and biofuel production to therapeutics and diagnosis. In addition, the proposed study will increase our fundamental understanding of protein functions under confinements and explore unconventional enzyme activities in artificial local environments. These will help the construction of chaperone-like compartments for stabilizing proteins in noncellular environments. In line with Army goals, the project outcomes will provide the scientific foundations for future development of smart nanoreactors to achieve functions such as feedback regulation and gated transmembrane diffusion. The synthetic compartments to be explored in this project will find future utility in applications of revolutionary catalysis, bioenergy storage and conversion, and bio-target sensors. The proposed research will aid the development of adaptable platforms on which biocatalysis, biofuel production and biosensor devices can be integrated, activated and regulated. This will harness new capabilities to enhance warfighter protection and performance.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 01, 2019
- Source ID
- W911NF1910240
Entities
People
- Jinglin Fu
Organizations
- Army Contracting Command
- Rutgers University
- United States Army