1. Competition Deliverables:
Convince the judges that you have completed the following Competition Deliverable
✔Wiki
✔Project Promotion Video
✔Team Presentation
✔Judging Form
2. Attributions:
Describe what work your team members did and what other people did for your project.
In order to applaud every individual, community, or organization that has contributed to our project, we have compiled their work on the Attribution section of our wiki. We made sure that on this page, we have presented the specifics of their work as well as their contribution to our project, Engine of Starlight. The contribution of every team member was written in chronological order based on the group that they belong to, and reflections have also been taken into account. Although we were not able to present every detail of what each member worked on, every critical step has been covered. Moreover, assistance from every individual, community, or organization was presented as well, both in the Attribution section and on all pages that consist of the related activities. Therefore, we think that we have met this criterion.
3. Project Description:
Describe how and why you chose your iGEM project.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a 1 percent prevalence worldwide. The etiology of ASD remains unknown and likely involves a wide range of environmental factors, complicating its treatment. In the previous two years, team NJMU-China has provided diagnostic and therapeutic assistance to autistic children. This year, we decided to further our efforts in ASD treatment. Emerging evidence has indicated the importance of mitochondrial dysfunction in ASD pathogenesis. Our pathway enrichment analysis also revealed the connection between autism and energy metabolism. Moreover, in our interview with parents of autistic children, we found a need for supplements of gut-microbiota-related metabolites. Based on the above background, we designed four systems to detect and alleviate mitochondrial dysfunction in autistic children. The engineering bacteria in Systems one and two, aiming at improving mitochondrial function, were our main focuses and will be delivered through microencapsulation in System 3, while System 4 is an L-lactate testing strip.
4. Contribution:
Make a useful contribution for future iGEM teams.
We think that we have met this criterion because, firstly, we created ten new basic parts and four composite parts, measured them, and documented their characteristics on the iGEM registry page. Secondly, we made five handbooks, including The Scientific Research Skills Handbook, The Laboratory Safety Handbook, The Lab Equipment Handbook, The Experiment Handbook, and The Synthetic Biology Handbook. The handbooks are available in both Chinese and English and can be previewed or downloaded for further reference. We also collaborated with other iGEM teams to form the Gut Alliance and developed an open platform for future iGEM teams worldwide to share gut-related problems they come across. In addition, we organized the Learn with Us program for students in our school, educating them on synthetic biology and scientific research. In terms of human practices, we also developed approaches that future teams may find useful as they carry out their HP activities.
1. Engineering Success:
Demonstrate engineering success in a part of your project by going through at least one iteration of the engineering design cycle. This achievement should be distinct from your Contribution for Bronze.
We have gone through at least one iteration of the engineering design cycle in each system. For system 1, we designed the engineering bacteria to boost NAD+ levels, successfully amplified the PncA gene from L168, constructed the pLDHLH673-PncA expression system in Lactobacillus plantarum L168, and tested its function indirectly. For system 2, we aim at preventing the possible accumulation of heavy metal ions in autistic children. We successfully constructed and transformed the plasmid pET28a-MT to Escherichia coli Nissle 1917 and tested its functions through various experiments. For system 3, we designed a drug delivery system through microencapsulation. We took electron micrographs to prove the successful building and calculated their survival rate in simulated gastrointestinal fluids for functional testing. For system 4, we aim at sensing the elevated lactate levels to detect mitochondrial dysfunction. We successfully constructed and transformed the plasmid ALPaGA-lacZ to Escherichia coli Nissle 1917 and test its function by observing the color reaction on filter paper. For each system, we also concluded our successes and failures at every step and made plans to learn and improve.
2. Collaboration:
Collaborate with one (or more) 2022 iGEM team(s) in a meaningful way.
We think we have met this criterion since we have collaborated with many iGEM teams in our country and around the world during our time as iGEMers. All of our team members value collaboration, and we took the opportunity to participate in collaborations of different forms, including meetups, lectures, and merch designing. Meanwhile, we hosted several activities so that other iGEM teams would hopefully benefit from them as participants. Besides our partnership with iGEM WHU-China and NAU-China, we also joined our fellow iGEMers in the NIA meetup, the Global Meetup, and three meetups in education. In addition, we cooperated with iGEM NFLS_Nanjing in a discussion on biosafety and established the Gut Alliance with eight other iGEM teams. Together, we developed an open online platform for teams focusing on the human gut. More details are available in the Collaboration section of our wiki.
3. Human Practices:
Explain how you have determined your work is responsible and good for the world.
We have designed our human practice approaches to push the project forward, help people with ASD, support parents of autistic children, and promote synthetic biology. Specifically, we realized that supplements were great expenses for families with autistic children from our visits to surrounding communities and, based on literature research, decided to focus on mitochondrial dysfunction to treat ASD. After deciding upon the subject, we handed out different questionnaires to parents to determine whether we were going in the right direction. We also held fortnightly seminars to share our reflections on previous works and have interviewed experts to further improve the project. The project was modified through communication with other iGEM teams as well. In terms of output, we organized various forms of educational activities and stepped forward into entrepreneurship by developing two business plans and a piece of hardware. Thus, we believe that we have met this criterion.
4. Proposed Implementation:
Explain how you would implement your project in the real world.
Before launching the project, we conducted thorough research, including related laws, biosafety and bioethics, and the acceptance of synthetic biological products among our target audience. The comment from professionals, doctors, and autistic people and their families benefited us a lot at this stage. Since our end users are mainly children with ASD, we handed out questionnaires to their parents to learn about their willingness to use our product, and the result was positive. We also interviewed biotechnological companies to test the feasibility of implementation and learn about the market. After several discussions and revisions, we came up with a relatively comprehensive business plan for the bacteria aimed at treating mitochondrial dysfunction and designed a piece of hardware for the testing strip. Safety was of paramount importance to us as well and we evaluated our conduct based on related regulations at every step. More details can be found on the Implementation page.
1. Integrated Human Practices:
Demonstrate how your team responded to your human practices reflections, research, and/or engagement. You should show how your activities impacted your project purpose, design, and/or execution.
We made sure that our human practices played a role at different stages of our project and gave us a better look at its influences on the world. We have reached out to people of different social and educational backgrounds throughout the season to have a better understanding of our project and gain more insights to make improvements accordingly. Understanding the experiences of professionals and patients and getting their feedback about our project comes first on our list. In this process, we found support for the designing, execution, and overall goals of our project through communication with stakeholders, experts, and parents of autistic children. We also networked with other teams and progressed with them. Meanwhile, we prioritized related education because we saw the importance of public awareness during our human practices. We believe that we have met this criterion and more details are available in the Integrated Human Practice section.
2. Improvement of an Existing Part:
Make a new Part that improves the function of an existing Part. This improvement must be distinct from your work for Bronze and Silver medals.
Enter the part number for the existing part you are improving in the box below:
Part Number: BBa_K2578811
Enter the part number of your new part in the box below:
Part Number: BBa_K4205000
3. Project Modeling:
Use modeling to gain insight into how your project works or should be implemented. Explain your model's assumptions, data, parameters, and results in a way that anyone could understand.
Our work in modeling included two analysis modules: structural analysis and mathematical modeling. Structural analysis refers to the analysis of the 3D structure of proteins and nucleic acids, including protein-protein, protein-small molecular compound, and protein-nucleic acid complex. Since the experimental protein structures deposited in the public dataset account for only a fraction of existing protein sequences, there is a need for efficient computational protein structure prediction, such as homology modeling, comparative modeling, and threading techniques, to explore potential functions of proteins outside the scope of the public dataset. Mathematical modeling models the biological dynamics of the engineered bacteria mathematically. Given certain experimental findings, we can build a series of the ordinary differential equation to depict the functional role of the engineered bacteria, upon which we were able to predict the outcomes of applying the same engineered bacteria under similar scenarios.
4. Proof of Concept:
Expand upon your Silver medal work for Proposed Implementation and develop a proof of concept for your project.
Based on our Silver Medal work of Proposed Implementation, we went further to prove our concept in the following four aspects: literature research, lab work, human practices, and implementation. Our efforts in literature research laid solid foundations for the project and helped push it forward. In terms of wet lab work, we have designed and carried out experiments to demonstrate the functions of the four systems and have received promising results. Additionally, structural analysis and mathematical modeling helped us in the verification of the functions as well. Human practice activities, inputs and outputs included, also assisted in the iteration process. Finally, beside a piece of hardware for the testing strip, we also 3D printed the test kit and made an instruction manual to further prove the concept, and in order to modify the business plans, we contacted more experts and received positive feedback from entrepreneurs and experts.
5. Partnership:
Collaborate throughout the year with at least one other 2022 iGEM team on a set of shared objectives related to both of your projects. This partnership should go beyond a Silver medal collaboration.
We think that we have met this criterion because we have established close partnerships with two other iGEM teams, iGEM WHU-China and iGEM NAU-China, throughout the season. We kept in close touch with the two teams throughout the season, and our cooperative activities helped shape our projects at different stages, including ideation, design, demonstration, modification, commercialization and art & design. All of the teams were able to make improvements to their projects based on the questions that the other team posed during the meetups. Our collaborative work also involved modeling and different aspects of human practices as well as design. Due to the pandemic, we held most of our meetups online via Tencent Meeting. This, however, doesn't mean that the experiences were not enjoyable and unforgettable, nor does it mean that the mutual learning experiences were not valuable for all of us. More details are available on the page for Partnership.
6. Education and Communication:
Develop and implement education, science communication, and/or outreach materials related to synthetic biology.
We made an effort to educate and develop opportunities for individuals of all age groups and backgrounds in four main aspects: synthetic biology, ASD, basic skills in scientific research, and other subsets of biology. We were determined to create an inclusive environment where everyone involved could have fun while learning and tried our best to provide follow-up support for anyone who showed an interest in these areas. When designing our activities, we made sure that the materials and objectives were adjusted each time to match the specific group. In addition, we made feedback questionnaires for each activity to revise and improve it based on the feedback comments collected and double-check that we were following the safety policies. Our aim was to promote mutual learning experiences and encourage open dialogues among our audience. We also developed a strategy for all educational activities to follow. Therefore, we think that we have met this criterion.
