Date: May 13th, 2024
Time: Monday evening, 18:00
Location:Xuehai Building A435, Jiangning Campus, Nanjing Medical University
On May 13th, 2024, after joint discussions, NJMU-CHINA and CHINA-HUBU-WUHAN co-hosted an exchange meeting. The exchange focused on the content, progress, and team-building aspects of each project, where both teams enthusiastically shared their experiences and explored ways to improve.
Details:
1. Project Introduction
This year, NJMU-CHINA's project is "Memory and Happiness Puzzle" – an engineered bacterium for treating brain neurological diseases.
By modifying Lactobacillus plantarum L168, the bacteria can release tetrahydrofolate and theanine, which help alleviate Alzheimer's disease (AD) symptoms. Recent studies have found that the interaction between LirB3-APOE4 can activate interferon-stimulated genes, impairing microglial phagocytosis and promoting amyloid-beta (Aβ) deposition, thereby increasing the risk of AD. Using molecular docking (AutoDock) and surface plasmon resonance (SPR Biacore) technology, the team identified tetrahydrofolate, a gut microbial metabolite, as an effective LilrB3 binder. Studies also showed that theanine significantly alleviates AD symptoms. By integrating key enzyme gene sequences and a suicide switch, the team engineered Lactococcus lactis L168 to produce tetrahydrofolate and theanine. Once ingested, this engineered probiotic reaches the gut, releases these compounds, and enters the brain via the gut-brain axis. Tetrahydrofolate binds to the LilrB3 receptor, blocking the APOE4 interaction, inhibiting Aβ deposition, and thereby improving AD symptoms.
The NJMU-CHINA subgroups shared their current progress. The experimental group introduced their experimental design, progress, and results, while the HP (Human Practices) group shared their human practice activities, especially the synthetic biology education sessions conducted in primary schools, which received widespread praise from teachers and students. The modeling team also discussed the challenges they faced during the modeling process.
This year, CHINA-HUBU-WUHAN's project is "Multiple Effects of One Bacterium -- Synbiotics Microbial Therapy."
Their project mainly focuses on using synbiotic microbial therapy to treat diabetes and hypertension patients. Through an oral delivery system, the GRAS strain ZMO is delivered into the body, where it expresses in E. coli, self-destructs, and releases the drug to take effect. The modeling team primarily used Swiss-model for structure prediction, Schrodinger software for molecular docking, and Hawk Dock for docking.
The CHINA-HUBU-WUHAN experimental group, modeling group, and HP group shared their current progress as well. The experimental group introduced their experimental design, progress, and encountered problems, as well as lessons learned from previous experiments. The HP group shared their product commercialization strategies and stakeholder interview designs, while the modeling team discussed the algorithms they studied and their application to their project.
2. Open Exchange
During the free exchange session, members of NJMU-CHINA and CHINA-HUBU-WUHAN discussed the issues they encountered in the experiment and modeling process, offering constructive suggestions to each other. Both teams also engaged in in-depth discussions on HP activities and project promotion. We are especially grateful to CHINA-HUBU-WUHAN for their valuable suggestions regarding our experiment and human practice activities, which not only broadened our perspectives but also inspired future activity designs. Through this exchange, we solved numerous practical problems, gained new collaboration opportunities, and further strengthened the friendship and cooperative spirit between the two teams.
Meanings:
The exchange concluded successfully, and our team gained valuable insights into practical project design from the other team, which we will use to continuously improve our own project. We extend our gratitude to the students from Hubei University and hope for more opportunities to exchange and share with other teams in the future.
Date: July 14, 2024
Time: 10:00
Location: Business School, Xi'an Jiaotong-Liverpool University, Suzhou
During the CCIC conference, we engaged in an in-depth exchange with the XJU-CHINA team, where everyone freely shared their thoughts. We discussed potential future collaborations in Human Practices (HP), as well as exchanged experiences in experimental and modeling aspects.
Details:
Firstly, we presented our project, "Memory Puzzle," detailing our work on an engineered bacterium designed to treat neurological brain diseases. Our team focused on developing a modified Lactobacillus plantarum L168, capable of releasing tetrahydrofolate and theanine to alleviate Alzheimer's Disease (AD) symptoms.
The XJU-CHINA team then introduced their project: a polyethylene microplastic crusher. They are exploring a sustainable and convenient method for degrading polyethylene (PE). Through literature reviews, database screening, and simulated molecular docking, they identified enzyme gene sequences with a strong affinity for PE. After bacterial engineering and heterologous expression, they evaluated the enzymes' PE degradation capabilities.
The XJU-CHINA team demonstrated a comprehensive HP workflow, from initial investigation to practical feedback and conclusion dissemination, forming a logical loop. In contrast, our current HP activities lack purposeful preliminary research. It is essential for us to conduct targeted interviews with experts and stakeholders centered around depression and AD, supplemented by questionnaire surveys and relevant analyses. Additionally, our HP activities and design must be closely integrated with our overall team project.
Regarding modeling, we observed that many teams utilized molecular docking methods, prompting us to refine our existing work and complete metagenomic analyses, identifying suitable cohorts for comprehensive analysis.
In the experimental aspect, we learned that they designed 23 plasmids to compare effectiveness and have already completed 5, demonstrating rapid progress despite the large workload. This encourages us to accelerate our experimental progress, aiming to finish all plasmid experiments, complete the construction of engineered bacteria, and validate the self-destruct switch with cell experiments during the summer.
Significance:
The XJU-CHINA team’s approach to screening small molecules, validating them through molecular docking, and introducing plasmids into bacteria for mass production closely aligns with our strategy. Although our projects aim to address vastly different issues, the exchanges in HP, modeling, and experimental aspects were incredibly enriching for us. We look forward to more online exchanges and collaborations in the future.
Date: July 14, 2024
Time: 10:00
Location: Business School, Xi'an Jiaotong-Liverpool University, Suzhou
During the free exchange session at the CCIC conference, we had an in-depth discussion with the team from Tianjin University, where everyone spoke freely about potential future collaborations in HP, as well as shared experiences in experiments and modeling.
Details:
First, we introduced our project briefly. This year, our project, "Memory Puzzle," focuses on developing an engineered bacterium to treat neurodegenerative diseases. We modified Lactobacillus plantarum L168 to release tetrahydrofolate and theanine, aiming to alleviate symptoms of Alzheimer's Disease (AD).
The TJUSX-CHINA team’s project involves using an innovative drug delivery platform based on a network of probiotics adhesion and interaction. They designed a “Microbe Spidey” super bacterium, including Escherichia coli Nissle 1917 and Lactococcus lactis F44 strains. Through a biotin-avidin-based intestinal adhesion system and a quorum sensing-based interaction system, this probiotic functions like "Spider-Man," forming a "web" within the intestine to overcome the challenges of weak colonization and complex interactions among microbial communities. This approach has the potential to significantly impact gastrointestinal diseases and gut-brain axis research.
The TJUSX-CHINA team excels in online science popularization with diverse formats, which inspired us to prioritize online outreach and promptly update and share our activities. In terms of modeling, the TJUSX-CHINA team closely integrated their dry lab and wet lab experiments, demonstrating the concept of using modeling to guide and optimize wet experiments continuously. Some teams even showcased innovative ideas, such as incorporating electronic concepts into their designs, while our team’s focus on a more unique disease stands out.
Regarding experiments, the TJUSX-CHINA team designed plasmids involving complex genetic circuits, with various switches interacting and inducing responses, presenting a highly novel concept. However, ensuring that each component functions correctly in such a complex design is key to achieving the desired results, requiring substantial effort in the validation process—something we can learn from.
Meanings:
Both the TJUSX-CHINA team and our team are focused on neurodegenerative diseases and the gut. There are numerous aspects in HP, experimentation, and modeling where we can learn from and exchange ideas. We look forward to further interactions and collaborations in the future.
Date: July 27th,2024
Time: 17:00
Location: Shared Tearoom.Nanjing.China
On July 27, 2024, after mutual consultation between both universities, NJMU-CHINA and NAU-CHINA jointly held an exchange meeting. The team members from both sides engaged in in-depth discussions about their respective projects' content, progress, and team building, eagerly sharing their experiences and exploring areas for improvement together.
Details:
1. Project Introduction
Firstly, team members from both sides conducted brief introductions to their projects. The NJMU-CHINA team introduced the "Memory Puzzle" project, providing a detailed explanation of our engineered bacteria designed for treating neurodegenerative brain diseases this year—modified Lactobacillus plantarum L168, which is capable of releasing tetrahydrofolate and theanine to alleviate symptoms of Alzheimer's disease (AD). In addition, our team's modeling and HP groups presented their current progress and the technical challenges faced, which piqued the interest of NAU-CHINA team members, who also raised some questions and suggestions about our project.
Subsequently, members of the NAU-CHINA team introduced their project for this year: SAMUS: Self-healing Adhesive Materials for Underwater Soft-robot. NAU-CHINA aimed to address the issue of soft robots being easily damaged in the complex and ever-changing marine environment by developing a new material with excellent self-healing capabilities. This material would help underwater soft robots repair themselves after damage, significantly extending their lifespan and providing strong support for ocean exploration. They created a fusion protein as a "double-sided adhesive" by combining mussel foot proteins with squid ring teeth proteins, allowing the self-healing material to adhere firmly to the substrate. Additionally, they designed a circular mRNA using the RNA self-cleaving ribozyme mechanism to produce highly repetitive squid ring teeth proteins. These proteins form a network structure through β-sheet interactions, enabling self-repair after damage. The NAU-CHINA experimental, mathematical modeling, and HP groups also shared their current progress.
2.Open Exchange
During the open exchange session, members of NJMU-CHINA and NAU-CHINA discussed problems encountered in their experiments and mathematical modeling processes, and both sides offered constructive suggestions. The two teams also engaged in in-depth discussions on HP activities and project promotion. Special thanks to the NJMU-CHINA team for their valuable advice on our integrated human practices, which not only broadened our perspective but also inspired future activity designs. Through this exchange, we not only resolved numerous practical issues but also discovered new opportunities for collaboration, further strengthening the friendship and cooperative spirit between the two teams.
At the end of the exchange, both teams enhanced their friendship through board game activities. In a relaxed and lively atmosphere, the offline exchange concluded perfectly, laying a solid foundation for future collaboration.
Meanings:
This inter-university exchange meeting not only deepened the mutual understanding between the two universities but also sparked new inspiration for the iGEM teams, fostering continuous mutual learning and encouraging innovation. It effectively built a bridge for communication between the two universities. During the meeting, everyone freely expressed their ideas, raised questions, and offered suggestions for each other's projects. We hope that in the future, both university teams can work together, support each other, and move forward hand in hand.
Date: July 14, 2024
Time: 10:00
Location: Business School, Xi'an Jiaotong-Liverpool University, Suzhou
During the CCIC, we had an in-person exchange with the China Pharmaceutical University (CPU-CHINA) team. We introduced each other's projects and shared the work done by each group, exchanging experiences in experiments and modeling. We also discussed plans for deeper collaboration in Human Practices (HP) and the future of synthetic biology.
Details:
Firstly, we introduced our project to the CPU-CHINA team: "Memory Puzzle" — an engineered bacterium designed to treat neurological brain diseases. We detailed our work on developing an engineered Lactobacillus plantarum L168 to release tetrahydrofolate and theanine, which aims to alleviate symptoms of Alzheimer's Disease (AD).
Next, the CPU-CHINA team presented their project, which focuses on a treatment for Fusobacterium nucleatum (Fn)-mediated colorectal cancer (CRC). They have engineered Bifidobacterium longum (BL) capable of simultaneously eradicating cancer cells and pathogens, aiming to create a more affordable and effective probiotic solution for colorectal cancer treatment.
Our exchange centered around experimental aspects. We observed that many teams designed plasmids with complex genetic circuits, incorporating various interacting switches and induction relationships, which were quite innovative. However, ensuring that each component functions correctly under such complex designs is crucial to achieving the final outcome, and this requires substantial effort during the validation process — something we found worth learning from.
Moreover, regarding the self-destruct switch, many teams still utilize common switches such as the arabinose switch. In contrast, our self-destruct switch is relatively more novel and could be considered a highlight, potentially qualifying us for the Best Composite Part or Best Safety Award. Additionally, unlike the Bifidobacterium used by the CPU-CHINA team, no other team has adopted Lactobacillus plantarum so far, which remains a distinctive innovation for us, deserving a detailed introduction on our wiki.
Significance:
During the exchange, everyone freely expressed their views, raising questions and suggestions for each other's projects. We gained numerous insights and inspirations for our presentation and wiki work. This exchange not only deepened our mutual understanding and cooperation between the two universities but also heightened our expectations for more offline interactions in the future, fostering further collaboration in HP, experimentation, and modeling.
The Conference of China iGEMer Community (CCiC) is a national exchange meeting initiated independently by iGEM teams in China, aiming to provide a platform for resource sharing, mutual learning, and exchange among iGEM teams and synthetic biology enthusiasts across China.
From July 12 to 14, our team attended the 11th CCiC at the Business School of Xi'an Jiaotong-Liverpool University. At the conference, we gathered with iGEM teams from across China to exchange ideas, share project designs and progress, and engage in intellectual discussions. After presenting our project, the guests and judges asked targeted questions and provided suggestions, such as questioning the causality in our research. This feedback made us realize the importance of clearly explaining the link between gut microbiota imbalance and neurological disorders in our PPT background introduction. Additionally, experts and scholars in the field of synthetic biology delivered keynote speeches and participated in roundtable discussions on topics like future commercialization, providing us with new perspectives and directions.
During the free exchange sessions, we had face-to-face discussions with teams from universities such as Northwest University, Xinjiang University, and China Pharmaceutical University, sharing ideas on HP, modeling, experiments, and overcoming technical challenges. Through these interactions, we constantly reflected and learned. For instance, our exchange with China Pharmaceutical University made us realize the importance of clearly explaining the advantages of our engineered strain compared to directly ingesting small-molecule drugs and other strains used by other teams. While communicating with Xinjiang University, we noticed that many teams employed molecular docking techniques, which highlighted the need for us to not only refine our existing work but also complete metagenomic analyses, streamline our thought processes, and tell our story more effectively.
Participating in the 11th CCiC not only deepened our understanding of our project and plans but also strengthened our connections with other iGEM teams, establishing good collaborative relationships with several universities. We will maintain these connections and continue to participate in future exchange activities.
Date: July 28, 2024
Time: 16:00-17:30
Location: Online
To enhance communication among iGEM teams and authentically showcase the challenges and solutions encountered in the process of independent learning and innovation, 12 teams, including ZQT-Nanjing and BNUZU-China, jointly explored the boundaries of technology and ethics. The meeting was attended by experienced iGEM coach Mr. Liu and esteemed education expert Mr. Zhao, who provided feedback and guidance. Throughout the meeting, we freely exchanged ideas with other teams and instructors, sharing our experiences and insights in HP and experimental processes.
Details:
During the meeting, we mainly discussed our HP and experimental approaches.
HP (Human Practices):
Our HP approach is divided into three phases: research discovery, practice feedback, and conclusion dissemination.
In the early stages, we conducted purposeful research surrounding our team’s design, including expert interviews, stakeholder visits, questionnaires, and appropriate analysis. During this process, we identified issues such as the living difficulties faced by depression patients and societal misunderstandings about depression. With these issues in mind, we designed and conducted a series of practical activities. These activities ranged from engaging children to the elderly and included online and offline events, where we promoted synthetic biology and raised awareness about depression. We also volunteered at depression rehabilitation centers to interact closely with patients.The feedback obtained during the practice process was addressed through expert interviews, exchanges with other teams, and continual improvements to our practice design. Eventually, the refined activities were shared, such as publishing a series of educational videos online, thereby forming a logical closed loop from research discovery to practice feedback and then to conclusion dissemination.
Experiments:
First, during the experimental design phase, reasonable design is key. We emphasized setting appropriate control groups, including both negative and positive controls, to ensure the reliability of experimental conditions and avoid false-positive or false-negative results. We also stressed the importance of reproducibility, conducting multiple repetitions to ensure data accuracy.
Second, during experimental operations, we strictly adhered to Standard Operating Procedures (SOP). Every step, from reagent preparation to sample handling, was executed precisely to minimize human error, using high-precision pipettes to ensure consistent volumes. Additionally, we employed automated equipment to reduce human error. We carefully selected appropriate experimental methods, consulting literature to ensure that each method was validated and suitable for our purposes, especially in critical steps like DNA extraction and protein expression. Lastly, our team prioritized timely data analysis and feedback. After each experiment, we immediately analyzed the data using statistical methods to assess the significance of the results, identifying any anomalies and making necessary adjustments.These measures helped us effectively control experimental errors, ensuring the reliability of our iGEM project outcomes.
In terms of experimentation, we asked the team from Southern Medical University about using toxic bacterial strains. They responded that they selected a non-toxic Corynebacterium strain that survives only in mangrove soil, ensuring it posed no health risks to humans and addressing ethical and safety concerns. Regarding HP activities, we listened to the Zhejiang University of Technology team’s experience in conducting HP work and gained valuable insights.
Meanings:
This SCL roundtable meeting provided a platform for us to present our latest research achievements and share experiences, promoting communication and collaboration between different teams. We had the opportunity to hear expert opinions on our HP and experimental approaches, broadening our perspectives, deepening our understanding of synthetic biology, and providing us with a clearer direction for future HP and experimental work.
