Team:TokyoTech/HP/Gold Integrated

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iGEM Tokyo Tech

Gold: Integrated Human Practices


Overview


By integrating with our Human Practices and the results from our wet lab experiments and modeling, iGEM2017 Team TokyoTech have executed our project with improved design in accordance with comments from general public, and have strengthened the public engagement of a two-way dialogue between our team and the public through this summer. (See here to know how we integrated our project)


How did we integrate them?


Fig. 1 Roadmap of integrated human practices

At an early stage of our project design, we decided to establish co-culture system between bacteria and human cells regardless of the practical application. For 10 years, our team has used E. coli for the project. However, we had to use something new to adopt a paradigm shift in iGEM community. Thus, we added human cells to explore the interaction between them in our body. Also, as described in the Project-Description page, biological activities of a human are maintained by both human and bacterial cells. In this context, the artificial co-culture systems in vitro must be paid more attention, but such systems have hardly developed so far in synthetic biology. Now, it is the time to change mind from single to multi species culture! Otherwise, we may misunderstand biological activities!!


In May Festival held in University of Tokyo, we introduced our project to the general public in the poster session. The audiences gave us a lot of advice and valuable comments that later led us and our project to move forward. One of them advised us that we should apply the project for the field of therapeutics. That advice opened up a door for the application of our project which had hovered up a level of fundamental research.


We had planned to use Caco2 cells derived from intestine, but our PI advised us that EA.hy926 cells derived from vessels are better for the therapeutic application. For example, there is an idea in which bacteria are utilized as conveyers of therapeutic agents. To this end, bacteria should be delivered to the diseased part like cancer tissue through blood vessel. Therefore, we considered that sustainable and safe settlement of bacterial cell to endothelial cells is important. We accepted that advice and started to culture the EA.hy926 cells and transduced the artificial gene circuits.


Our PI gave us a chance to discuss the direction of our project with the experts from molecular biology in Keio University. At that time, our project had a problem of what we call "Cross-talk." In this case, cross-talk means that the signaling molecules from the transduced human cells are unexpectedly accepted by other native human cells; the signaling should take place only between the transduced human cells and bacterial cells. Some of the experts suggested to us that we should use a plant hormone to prevent it, because such plant hormones are expected to be accepted hardly by native human cells.


Based on the advice from the experts, we decided to use iP(Isopentenyl adenine) as the alternative signaling molecule from human cells to E. coli.


Interaction between HP and Experiment


Fig. 2 Roadmap: How we integrated Human Practices and our experiment

From our full year experience in iGEM, we realized the necessity of verifying from a different point of view. In other words, we realized that we researchers ourselves must also continuously reflect on the risks and costs and benefits of the researches. In the workshop that we attended as our initial activity in iGEM, we learned from social scientists, the danger of grounding on the deficit model, which fixes on the idea that the general public is ignorant, and the importance of the two-way dialogue between society and researchers.