2019 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 – 2021-03-31
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| Keywords | DNA Nanostructures / Molecular Robotics / Stochastic Simulations / Quality-Diversity |
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| Outline of Annual Research Achievements |
During this year, we (a) improved the algorithm for exploring structures and the simulation workflow, (b) generated sets of DNA strands capable of dynamically assembling into large structures, and (c) performed experimental validation, confirming the existence of those structures.
The algorithmic exploration was done on a set of three different libraries of DNA strands, with increasing complexity. We designed a framework to allow the automatic generation of reaction sets from candidate systems, which are then fed into a stochastic simulation algorithm. Promising solutions where then forwarded to Nupack, an algorithm for the prediction of DNA structures. Finally, promising systems were output for actual experimental validation.
However, validation was limited and did not give much details about the nature of the structures beyond the existence of large structures. Further experiments are required but were prevented by the outbreak of COVID-19.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
Preliminary experiments showed that candidate systems found by the algorithmic framework produce large structure. Moreover, real-time PCR experiments showed that the number of double-stranded DNA in the system increases non-linearly over time, showing that complex dynamics are at play, as expected from the simulations.
However, the closing of laboratories prevented us from performing additional experiments such as dynamic light scattering to evaluate the size of structures over time or AFM to allow us to see the shape of those structures. Despite the use of a cutting-edge model, we expect a large variability between the result of simulations and actual experiments.
Still, the preliminary results showed that our approach could successfully suggest DNA sets generating complex dynamics assemblies.
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| Strategy for Future Research Activity |
The main plan for the year is to perform the remaining experimental validation and submit to result as a research paper. However, due to the uncertain evolution of the COVID-19 situation, performing those experiments might be challenging. In that case, we will perform additional analysis of our simulation results and submit a research paper focusing mostly on the theoretical aspect of the project, using the experimental results as supplementary material evidence of the feasibility of the approach.
In both cases, we will use the remaining time on the project to streamline the approach, making it as automated as possible, and to provide documentation and tutorials for a wider audience. It is our hope that our framework can help the design and optimization of a wide range of molecular systems.
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| Causes of Carryover |
The remaining budget was aimed to cover experiments that had to be cancelled due to the COVID-19 pandemic. As the situation evolves, we are hoping to use the remaining budget for those experiments as they were originally planned. In particular, we aim to perform Dynamic Light Scattering evaluations of our experimental samples to estimate the size of structures produced over time.
In the case were the situation would prevent those experiments to be conducted in a timely fashion, we plan to use the remaining budget for presenting our current results at an international conference as well as for covering publication fees.
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