Team:Carnegie Mellon/Hum-Overview

From 2012.igem.org

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The impact of synthetic biology depends on the number and quality of scientists making significant contributions to the field. Future scientists will rise from current high school students who are excited about science and gain a solid background in math and science in their formative years. To this end, we decided to raise the awareness of high school students about the interdisciplinary field of synthetic biology and to also teach them about the process of scientific research.
As an additional outcome, the proposed methodology of using an electronic circuit equivalent for modeling biological phenomena can be replicated and used beyond the context of our current project.

We decided to create teaching materials for high school students inspired by our team’s research project. Our goal was that these materials can be easily used by a science teacher in a lecture in a Biology or Chemistry course to:

  1. Explain what Synthetic Biology is;
  2. Illustrate the opportunities created by Synthetic Biology in improving human well being;
  3. Discuss ethical concerns related to Synthetic Biology;
  4. Enable the students to understand how our biosensor works.

To bridge the gap between the background of a high school student and the complexity of our project, we built an affordable, microcontroller-based, hardware platform and associated, open-source, digital simulation software. In designing the demonstration platform, we exploited the relationship between biological networks in synthetic biology and electronic circuits in electrical engineering. Specifically, we created a circuit kit that emulates in hardware our biological construct and in software both the response of the biological construct to specific cell conditions and the fluorescence measurement. It is important to note that the kit is INTERACTIVE (students can easily change electronic components to simulate different biological or external changes and the outcome of these changes), RELATABLE (the students can directly use the kit) and EASILY SHARED AND IMPROVED (the list of electronic components, circuit diagrams etc. are in the public domain and the software is open source).

The teaching materials we have created, specifically a power point presentation and an electronic circuit kit, have become part of the Lending Library of Kits of DNAZone, the outreach program of the Center of Nucleic Acids Science and Technology (CNAST) at Carnegie Mellon. The kits in the Library are loaned to high school teachers in the Pittsburgh area to be used in teaching Math and Science. We identified for the teachers how the use of our kit can help the High School students meet specific objectives from the Pennsylvania Academic Standards for Science, Technology, and Engineering Education and the Pennsylvania Assessment Anchors. We have also tested the kit in several demonstrations in the Summer of 2012 to high school students enrolled in the Summer Academy of Math and Science (SAMS) at Carnegie Mellon.

A very important original property of our approach to Human Practices stems from the fact that the teaching materials we created are available to teachers in any Pittsburgh Public School District who can borrow them from the Lending Library of Kits and use them even after the work of the current CMU iGEM team ends. Another original factor is the fact that we identified for the teachers which objectives from the Pennsylvania Academic Standards for Science, Technology and Engineering they can teach using the kit. This identification should eliminate the barrier to adoption of the kit by teachers faced with tight time schedules to cover these objectives.

System Implemented with the Kit

As described here, our team engineered a fluorescence-based sensor that provides information on both transcription strength and translation efficiency of a promoter. The sensor is noninvasive, easily applied to a variety of promoters, and capable of providing results in a time frame that is short when compared to current technologies for the characterization of promoters.

The sensor is based on the use of an RNA aptamer (termed Spinach) and a fluorogen activating protein (FAP). The complexes of Spinach (mRNA-DMHBI in the Figure) and FAP (FAP-MG in the Figure) with specific dyes, DFHBI and MG, respectively, are fluorescent. Measurements of the fluorescence intensity of these complexes enables one to determine the concentration of mRNA and expressed protein for a given promoter. Analysis of the fluorescence data with an appropriate model leads to the transcription strength and translation efficiency for each promoter.

The goal was to create a model of our biosensor that clearly represents its main components and makes clear how the biosensor works. We also planned to enable the students to simulate changes in the “environment” and to observe the outcome of these changes. To achieve this goal, we built an affordable, microcontroller-based, hardware platform and also developed an associated, open-source, simulation software.

The combined hardware/software platform allows the students to directly manipulate electronic components, which are formal equivalents of the BioBricks used in our sensor, and to observe the effect of changing these components on the current or voltage output, which is the equivalent of the fluorescence intensity in our lab experiments. In using the kit, the students get a feel for how different promoters are compared using the biosensor; they can rank "virtual promoters" in the order of their strength. Students who use the kit gain hands-on experience and understand how all the parts of the biosensor work together to measure the mRNA and protein levels, without working in the wet lab. The figure on the right is a photograph of the hardware platform on which the correspondence between the biological components of the biosensor and the electronic components of the kit are identified.

The software used in the platform is based on the model derived for the analysis of the fluorescence data obtained with the biosensor. We have also created a GUI that allows the students to modify the parameters used in the model and to visualize on a computer display the current/voltage output (which is the equivalent of the fluorescence output in our experiments).

To obtain feedback for how high school students use the circuit kit, the team has given several presentations about synthetic biology and our project to high school students enrolled in the SAMS and in AP Biology at Carnegie Mellon University. We have also sought and obtained feedback on the kit from Dr. Janet Waldeck, Physics teacher at the Pittsburgh Allderdice High School in Pittsburgh. The feedback and input gained from these presentations was used to refine the kit.

Broader Impact in Biological Modeling Methodology

The methodology used to build the electrical equivalent of the biological processes is not unique to the problem we are solving in this project. Starting from first principles modeling, one can use the methodology followed in our circuit kit implementation and emulate the behavior of the processes governing other biological phenomena by using simple controllers and circuit components. This shows that interdisciplinary training is not only desirable, but can also be beneficial for solving synthetic biology problems, thereby underscoring the importance of such training starting from high school through college.

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