- author = "Anupama J. Thubagere",
- title = "Programming Complex Behavior in {DNA}-based Molecular Circuits and Robots",
- school = "Biology and Biological Engineering, California Institute of Technology",
- year = "2017",
- month = "23 " # may,
- keywords = "genetic algorithms, genetic programming, Bioengineering",
-
URL = "
https://thesis.library.caltech.edu/10323/",
-
URL = "https://resolver.caltech.edu/CaltechTHESIS:06082017-194534497",
-
URL = "
http://thesis.library.caltech.edu/10323/1/Anu_Thubagere_BBE.pdf",
-
DOI = "
doi:10.7907/Z9WD3XMS",
- size = "137 pages",
-
abstract = "Integrated electronic circuits, like those found in
cellphones and computers, are ubiquitous in our
information-driven society. The success of electronics
has, in part, been due its modular architecture that
enables individual components to be independently
improved while the overall device functionality remains
unchanged. Over the last two decades the emerging field
of dynamic DNA nanotechnology has been trying to apply
the underlying philosophy of electronics to biochemical
circuits. DNA nanotechnology employs rationally
designed DNA molecules as building blocks of
biochemical circuits that can, in principle, enable
powerful applications like diagnostics and
therapeutics.
Researchers in the field of DNA nanotechnology have developed simple elements to construct biomolecular systems with desired functions. They have also developed molecular compilers for defining design principles. The cost of DNA synthesis has decreased by over three orders of magnitude in the past decade. This has lead to a non-trivial number of small scale circuits, like DNA-based logic gates and chemical oscillators, being implemented. However, the scalability of this approach has yet to be clearly demonstrated.
In this thesis, we will discuss our main contributions to facilitating the advancement of DNA nanotechnology by developing systematic approaches for constructing modular DNA building blocks. These modules can be used to construct bio-chemical circuits and molecular robotic systems. The performance of the modules can be individually tuned and integrated into large-scale systems.
Using automated circuit-design software and cheap unpurified DNA, we demonstrated the design and construction of a complex synthetic biochemical circuit consisting of 78 distinct DNA species. The circuit is capable of computing the transition rules of a cell updating its state based on its neighbouring cells, defined in a classic computational model called cellular automata. Using a bottom-up approach, we first characterized the component necessary for basic Boolean logic computation. We then systematically integrated more circuit elements and eventually constructed the full circuit. By developing a systematic procedure for building DNA-based circuits using unpurified components, we significantly simplified the experimental procedure. By using unpurified DNA components, we reduced the cost and technical barrier for circuit construction, thus making the design and synthesis of complex.
Next we demonstrated a cargo sorting DNA nano-robot, using a simple algorithm and modular building blocks. The DNA robot has a leg and two foot domains for exploring a two-dimensional DNA origami surface, and an arm and hand domain for picking up randomly located cargos and dropping them off at their designated locations. It is completely autonomous and is programmed to perform a random walk without requiring an external energy source. Further, we demonstrated sorting multiple copies of two distinct cargo species on the same origami. Additionally, by compartmentalising each sorting task on a single origami, we showed that two distinct sorting tasks can be implemented on different origami simultaneously in the same test tube. The recognition of a cargo is embedded in its destination, therefore it is possible to scale up the system simply by having multiple types of cargos. The same robot design can be used for performing multiple instances of distinct tasks in parallel. The different modules can be integrated to perform diverse functions, including applications in time-release targeted therapeutics.",
-
notes = "Caltech
Anupama Thubagere Jagadeesh
Biology and Biological Engineering
Advisor: Lulu Qian Richard M. Murray (co-advisor)",
