2020 Fiscal Year Research-status Report
Natural selection driven structure building in a tunable DNA-only system
| Project/Area Number |
17K00399
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| Research Institution | Ochanomizu University |
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Principal Investigator |
オベル加藤 ナタナエル お茶の水女子大学, 基幹研究院, 助教 (10749659)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Keywords | DNA Nanostructures / Molecular Robotics / Robustness to failure / Quality-Diversity |
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| Outline of Annual Research Achievements |
During this year we finalized the complete workflow for the exploration of families of nanostructures that can be generated from specific DNA libraries. In this context, an (n,m) DNA library is the abstract list of all strands with N domains taken a set of domain sequences and their complementary sequence. The combinatorial explosion resulting from this definition prevents the exhaustive search of all possible combinations, except in trivial cases. Moreover, the time cost of performing experiments or even realistic simulations is prohibitive and greatly limits the number of systems that can be tested.
For that reason, the developed workflow works by refinement. At the first stage, we combine Peppercorn, a DNA reaction enumerator, with the MAP-Elites quality-diversity algorithm to find sets of strands with the potential to create a variety of structures. The most promising sets are then moved to the second stage, where we optimize the actual DNA sequence to maximize the stability of those structures. Finally, we analyze the properties of the reaction network that led to those structures and evaluate its robustness to the removal of reaction pathways.
We tested our framework on three libraries of incremental complexity, showing a connection between the number of individual domains and the variety of shape created.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
The full exploration framework has been finalized as planned and simulation results are promising. Those results have been presented to the DNA conference (international) and CBI conference (national) and an extended version is currently submitted as a research paper.
The original plan to perform experiments on the most promising sets has been cancelled due to the COVID-19 pandemic. We chose to focus instead on the analysis of simulation data, resulting in the creation of a third stage of our optimization framework (reaction network analysis). While that stage was not original planned in the research project, it provides additional valuable insights on the nature of the systems being optimized.
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| Strategy for Future Research Activity |
The plan for last year focus mostly on applying the current framework to additional libraries. One potential venue for extension would be the use of libraries with variable strand length. That approach is motivated by work on hierarchical self-assembly, showing a large diversity of structures that can be generated from as little as three independent strands. While such behavior can already be encoded by including "dummy" domains at the end of strands, a more direct encoding could help exploration.
Another venue of interest is the use of an automated experimental setup in collaboration with researchers from the Tohoku University, allowing us to add a new experimental step to the existing framework.
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| Causes of Carryover |
Most of the remaining funds will be used to pay the publication fees of the paper providing the latest results of the project.
We will also purchase DNA and buffer for performing experiments, depending on the evolution of the situation with COVID-19 and the availability of an online interface for online experiments.
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