Our integrated human practice embodies a journey of identifying social needs and challenges, devising appropriate solutions, engaging with a diverse range of stakeholders, and continuously refining our project in response to their insights and feedback. This transformative approach guides our project from a theoretical idea within the confines of the lab to a solution that is both effective for real-world issues and ethically sound.
To enhance the structure and clarity of our human activities, inspired by a previous INSA Lyon project, we used the Planet Model to observe all the environment's dimensions around an engineering tool and analyze the links and impacts between them. The entire frame work, based on the setting of a planet in universe and depicted in layers, from inside to outside, are Engineering, Economy, Society/Politics, Imaginary, respectively, which are also essential elements of a complete iGEM project. This methodology enables us to gain a holistic and systemic understanding of the entire project, including the technical part, and also wider economic, social and imaginary framework.
Firstly, in addressing the core Engineering problems, we engaged in a series of human practices. These practices involved comprehending the issue, exploring the possible materials and biological pathways for the solution, constructing the synthetic system and validating the anticipated functions with further, iterative improvements.
Surrounding the core is the Economy layer, which is the specific economic environment that our technical tool fits in. In this aspect, we researched companies involved in synthetic biology and current drugs for IBD, including their strengths and weakness, to get a comprehensive view of market viability. We also conceived a lot on commercial translation, managing to improve the aesthetic charm and also lower the expense of our product.
Outside is the Society/politics layer, connected to the ground and most people, where we considered the social relationship and impact of our project. Specifically, for therapy development, we focused on clinical application, doctors’ opinions, patients’ experience, biosafety and ethical concerns.
The outmost layer is Imaginary, the universe part surrounding the planet. It is about the motive that drives the people to opt for a specific type of product, economy, and policy. The decisions made by each society are influenced by their unique perspective on the world, which in turn molds their perception of the role of humans in the global ecosystem. The imaginary part runs through the whole project, from background research, concept design, to human activities, we always take this part into consideration, and it also comprises the unique feature of our project.
A significant number of people have participated in our process of engineering, economy, society/politics and imaginary. We can categorize them into four types: Expert, Entrepreneur, Partner, User.
Intriguingly, when we initially were brainstorming, we started from the imaginary and social need-the traditional culture of burning incense and its miraculous effects, and a call for long-term, non-invasive, patient-friendly drug administration. We designed our synthetic system based on our goal, and it was like constructing a planet in the imaginary universe. And when we were implementing our project, going from engineering to economy, society/politics and imaginary-from the basic core to the ground, and then to the imaginary sky, we kept reflecting on our engineering design and improving it through the information we collected, finally resulting in a product that integrated lab concept, social reality and its expectations. Also, by deploying the Planet Method, we can have an organized view of how we integrated knowledge from different fields into our project, ensuring a true understanding of the project and its interaction with real world from a comprehensive perspective.
Takeaway
The group gave utmost importance to safety training prior to commencing the experiment, tackling laboratory safety concerns even within the context of a level 1 microbiological lab. The experienced mentorship of Li Peng, coupled with the implementation of tailored laboratory rules, guaranteed a high level of safety awareness and curtailed potential hazards throughout the research. Moreover, Dr Li Peng also served as a supervisor and gave us expert suggestions on project design, yeast cultivation and experimental procedures.
Who
Li Peng, the secondary PI of the Tsinghua iGEM team with rich experience.
Why
After determining two possible topics, we were going to enter the pre-experiment phase. To maintain a high level of biosafety, we were required to go through a safety training first. Our lab was a level 1 microbiological lab with a level 2 biosafety cabinet, but there were still numerous potential areas for errors and non-standard operations, which could lead to safety hazards, diminished efficiency, and damage to the maintenance and hygiene of the lab. Therefore, Dr Li Peng, our secondary PI, arranged a biosafety seminar for us.
Dr Ling Peng had been the secondary PI of Tsinghua iGEM team for many years. Consequently, his expertise was exceptionally profound. To make it vivid and relatable, he showed us numerous photos of incorrect operations from previous teams, profoundly conveying his dissatisfaction. He also took us on a tour of the laboratory, pointing out the uses of each bench and refrigerator, explaining the standards for waste classification, and highlighting other potential areas for error. Throughout all subsequent experiments, we established the "last person" laboratory policy, where the last person to leave each day ensures that the lab is left in proper condition. Sometimes, when Dr Li Peng visited the lab and spotted any incorrect practices, he would also take photos and send them to our WeChat group to remind us. The safety and standardization of the lab have thus been firmly established.
Moreover, in the early stages of our Muscure project, since we chose yeast as the chassis organism, it was necessary for us to culture yeast. However, there were relatively few yeast laboratories at Tsinghua University, and we couldn't find a source to obtain yeast, nor did we know how to culture it. It was Dr Li Peng who provided us with the yeast strains he had preserved from the past and taught us how to culture them. Dr Li Peng also gave us his molecular biology laboratory manual, guiding us on the process of yeast transformation. During our initial meetings when we were selecting topics, Dr. Li Peng also listened attentively on the side, offering us advice on feasibility and other aspects.
Dr Li Peng provided us with tremendous support in terms of experimental safety, materials, and methods, largely laying the foundation for our project.
Takeaway
While brainstorming, inspired by Dr Ye Haifeng's research “AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation”, we investigated the possibility of muscone-induced microbe therapy and started our project.
Who
Ye Haifeng, Research Fellow, Ph.D. Supervisor, and Associate Dean of the School of Life Sciences, East China Normal University. He mainly utilizes the concepts and methods of synthetic biology to genetically modify and reprogram cells, and to redesign and construct intelligent gene network regulation systems for the precise treatment of diseases.
Why
During the preliminary brainstorming sessions, our group set its sights on developing an innovative therapeutic approach. We came across a study “AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation” conducted by Dr Ye Haifeng and got inspired. The idea of inhalational administration was particularly appealing due to its potential to mitigate the discomfort and inconvenience associated with other administration form, and it could even be a pleasurable experience. Buring incense could be an elegant act, and resonated with Chinese traditional culture well. We also found another article “Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells”, which engineered Escherichia coli Nissle to produce lactate in the intestine and limit T cell-driven CNS autoimmunity in encephalomyelitis. Combining these two discoveries, we started to contemplate the prospect of a long-term inhalational intestinal microbial therapy for autoimmune diseases.
Therefore, we contacted Dr Ye via email, hoping to get additional information and data of his research. In the email, we inquired if the muscone molecule could diffuse into the blood and permeate into other organs, and whether the whole system could be applied and work in microorganisms.
Dr Ye Haifeng responded enthusiastically to our inquiry. He was delightful to see our study on his article and acknowledged our innovation. In their research, they measured the concentration of muscone through liquid-phase and gas-phase mass spectrometers, revealing the concentration of blood, liver, and lung as 332nM, 444nM, 722nM, respectively. Regarding the system working in microorganisms, he pointed out the challenges and suggested experimental verification.
Dr. Ye's feedback bolstered our confidence in the viability of our project. The data given by Dr Ye was precious, which substantiated the possibility of our project. Meanwhile, his response underscored the importance of selecting an optimal microbial chassis and designing unique synthetic system in it.
Takeaway
Dr Liu Zhihua is an expert in intestinal homeostasis regulation, focusing on the interaction between host and microbiota. The team consulted Dr Liu Zhihua for the choice of yeast chassis. Dr Liu' s insights led to the attention on Saccharomyces cerevisiae, a safe and hugely studied yeast strain, and the relevant research “Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease”, which was quite inspiring for our project. We finally chose Saccharomyces cerevisiae to engineer, and deployed the innate mating pathway for our design.
Who
Liu Zhihua, Associate Professor of Tsinghua University School of Medicine, Editorial Board Member of 《Frontiers Cellular and Infection Microbiology》. She mainly explores the mechanism of intestinal microbiota-host interaction and develops strategies to promote intestinal homeostasis.
Why
When we encountered difficulties in determining the chassis, we communicated with Dr Liu Zhihua, an intestinal immunologist. She generously provided pragmatic suggestions and gave us great inspiration on pathway design.
Since the muscone receptor is a G-protein coupled receptor, and prokaryotes do not have G protein pathway, we could not use the EcN in the previous article and had to seek alternatives. While our understanding of the intestinal bacterial flora was extensive, our knowledge of fungi was limited. Therefore, we sought Dr. Liu Zhihua's expertise via email, inquiring about the yeasts that are resident in the intestinal tract, represent a relatively large portion of the microbial community, confer health benefits to humans, and are deemed safe for clinical applications. In consideration of experimental period and complexity, we also wished the yeast to be fast growing and well-studied, with readily available nutritional deficiency type. To conclude, the ideal chassis was required to be a eukaryotic normal flora in human intestine, with fast growing speed and mature culture method.
According to the thorough reply of Dr Liu Zhihua, Saccharomyces cerevisiae is one of the more abundant yeasts in the intestinal tract and is safer and less of a threat to human health than other more abundant fungi such as Candida. Moreover, as a model eukaryotic organism with a short growth cycle, Saccharomyces cerevisiae has a well-established culture and genetic transformation system, and a large variety of nutrient-deficient mutants that can be suitable for transformation screening with different vectors. She also recommended an article “Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease”, which reported on an engineered Saccharomyces cerevisiae probiotic that has the potential to help treat inflammatory bowel disease. She proposed that the strain modifications in the article could be used as a reference for our experimental design. The strain utilized the innate mating pathway of yeast and functionally linked the human GPCR P2Y2 with modified chimeric yeast Gpa1–human Gαi3 protein. In this way, the engineered yeast could secret CD39-like eATP-degrading enzyme apyrase and suppress experimental intestinal inflammation in mice. This study had been a great source of inspiration. We were struggling with how to design our own signaling pathway, which was complicated with cAMP, but after that we realized a well-defined and less-interrupted intrinsic pathway in yeast. We reviewed additional literature and summarized the methods to produce chimeric mating pathway.
The advice given by Dr Liu Zhihua was pivotal. We determined the strain and signaling pathway design, and the feasibility of the project was significantly validated.
Takeaway
Early in the project, we asked Mr Guo about the current status of using intestinal microbiota to heal autoimmune diseases, and verified the novelty of our project. At a later stage of the project, to ensure the biosafety, we aimed to design a suicide system in yeast. We sought a special intestinal marker, and the trigger of suicide when yeast loss the sense of this marker. We asked for Dr Guo Xiaohuan's suggestion, who is a professional in intestinal immunology and microbiota. He guided us to find metabolites of microbiota and other intestinal factors, and we eventually chose bile acid as the suicide marker.
Who
Guo Xiaohuan, Research Fellow, Ph.D. Supervisor, and Associate Professor of the School of Medicine, Tsinghua University. He has long been engaged in the study of intestinal mucosal immunity and intestinal flora regulation, and has elucidated the mechanism of action of intestinal flora and its metabolites affecting intestinal infections, inflammation as well as the efficacy of anti-tumor therapy.
Why
After we decided on healing autoimmune disease with intestinal flora, we wanted to learn more about the current state of this kind of treatment in the medical field. Since Dr Guo Xiaohuan is an expert in intestinal flora and immunity, we emailed him for consultation.
In Dr Guo's reply, he indicated that clinical studies on the use of intestinal flora to heal autoimmune diseases had not yet been seen, nor had cures been reported at the mouse level. We were exploring an innovative field. He also expressed concerns about the viability of the project, pointing out a number of challenges. In fact, we were not trying to completely cure IBD through intestinal flora, but achieving relief from IBD symptoms in an enjoyable and convenient way, which we were confident to accomplish through concrete design. After talking to Dr Guo, we were clear about the direction of our project.
Later in the project, in addition to the nutrient-deficient type, we felt the necessity to design suicide system to ensure biosafety. This would require an intestine-specific marker-when the yeast cannot detect this marker, it indicates that it has left the intestinal environment and needs to activate the suicide system. We were at a loss when searching for the intestinal marker, so we sent an email to consult Dr Guo again.
Dr Guo replied to us with patience. He first guided us to clarify the issue, whether we were looking for markers of the contents or the intestinal tissue, and recommended a literature “Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis”. After we determined that we needed markers of the content, he suggested some metabolites of microbiota and factors secreted by the intestinal tract, and reminded us to pay attention to the sensitivity of the sensing. In the end, we chose bile acids as our intestinal marker, and the yeast would activate the suicide system when it could not detect bile acids.
Throughout the course of our project, Dr Guo offered a wealth of professional and authoritative insights, which greatly enhanced the scientific rationality of our entire project design.
Takeaway
Challenges in drylab initially included establishing a model to validate the process of muscone diffusion in body. Valuable insights from Liang Xin, the professor of physiology in the School of Life Sciences, inspired us to seek the blood concentration of muscone and the knowledge of pharmacokinetics.
Who
Liang Xin, Associate Professor of School of Life Sciences, Tsinghua University.
Why
A critical aspect of the rationality of our project is to demonstrate that inhaling muscone can elevate the concentration of muscone in the intestines to a level that activates the yeast signaling pathway, meaning that muscone can effectively diffuse into the intestine. However, due to the inability to conduct animal experiments, this must be verified through modeling. Initially, on the WeChat, we consulted Dr Liang, who teaches physiology, to assess the possibility of muscone diffusing into the intestines.
After carefully listening to our ideas, Dr Liang offered several points of caution. First, we need to consider the pathways by which gases might diffuse into the intestines before proceeding with further calculations. Additionally, we should clarify the advantages of muscone inhalation compared to other therapies. In terms of advice, Dr Liang suggested that if quantitative calculations was challenging, we could estimate based on blood concentration reported in the literature—hydrophobic molecules could cross cell membranes, and their concentration in the small intestine might be similar to that in the blood vessels.
Dr Liang's insights were illuminating in our initial drylab experiments. We began to conceptualize the uniqueness of inhalational therapy and meticulously analyze the various pathways through which gas diffusion could occur, which allowed us to refine our understanding of how the therapy might work and to identify the key factors that needed to be considered in our research.
Takeaway
A chimeric mating pathway is essential for the function of engineered yeast, but challenges in protein design, involving the interaction between the receptor and G protein, were overcome with the guidance from Liu Cong, who is a senior in Tsinghua School of Life Sciences, and a previous iGEMer. He suggested us replace the five amino acids in the C terminal of Ga protein, and do codon optimization. We designed the chimeric amino acid sequence and constructed the vector.
Who
Liu Cong, undergraduate student at the School of Life Sciences, Tsinghua University.
Why
In the modification of the mating pathway, we had replaced the segment following the downstream promoter with ldhA, while for the upstream signaling, we must consider the interaction between muscone receptors and yeast G proteins. After reviewing the relevant literature, we summarized three potential approaches: First, without the need for protein modification, the muscone receptor may directly interact with the yeast G protein. Second, we could modify the terminal sequence of the G protein to facilitate its interaction with the muscone receptor. Third, we could induce error-prone mutations in the receptor and screen for mutants that can interact with the G protein. We were uncertain which method was the most reasonable. Knowing that our senior Liu Cong had experience with chimeric proteins, we decided to seek his advice via WeChat.
Our senior listened patiently to our queries. During the discussion, we broached the possibility and methods of creating a chimera by fusing yeast G-proteins with mammalian G-proteins. Our literature review had led us to understand that the key interaction between G-proteins and receptors only involved the five amino acids at the C-terminus, prompting our idea to replace the five amino acids at the C-terminus of the yeast G-protein with those from mammals. However, we were uncertain about this approach and wondered if we could directly substitute codons when designing the sequence. Liu Cong endorsed this method and advised us to perform codon optimization. At last, he also encouraged us to conduct experiments to validate our sequence design.
Liu Cong's response instilled a great deal of confidence in us. In the end, integrating the findings of our literature review with the senior's suggestions, we replaced the five amino acids at the C-terminus of the G protein. This approach was proven to be viable in the following preliminary experiments.
Takeaway
While verifying the concept of our project, the relation between lactate and immune regulation, especially DC function, remained a gap to be solved. In a conversation with Huang Kaifeng, a senior in Peking University Health Science Center, he recommended a relevant article “Downregulation of Membrane Trafficking Proteins and Lactate Conditioning Determine Loss of Dendritic Cell Function in Lung Cancer”. This article can serve as additional evidence for validating our project.
Who
Huang Kaifeng, a graduate student at Peking University Health Science Center.
Why
Because we initially read that literature “Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells”, considering that lactic acid was a substance that was relatively easy to produce, had a mild effect, and minimal toxic and side effects, we decided to use lactate as a downstream product to treat IBD. However, in people's perception, lactate is generally regarded as a food substance, and it is difficult to believe that it has the function of regulating the immune system. There was a gap to be bridged between lactate and the alleviation of autoimmune diseases, and we needed to search for more evidence.
The initial literature discussed how lactate inhibited the function of autoimmunity-related T cell subsets (e.g. Th17) by regulating the function of dendritic cells, thereby alleviating autoimmune diseases. Huang Kaifeng, a graduate student from the Peking University Health Science Center, came to our laboratory for an exchange research program. During one of the lab's discussions, I introduced our project to Huang Kaifeng and inquired about the rationality of using lactate as a therapeutic agent. Coincidentally, Huang Kaifeng had recently read an article about the inhibition of DC function by lactate and recommended it to me. That was “Downregulation of Membrane Trafficking Proteins and Lactate Conditioning Determine Loss of Dendritic Cell Function in Lung Cancer”. This undoubtedly added to the evidence, making our project more substantial.
Takeaway
We sought guidance on the physical delivery methods of muscone. Ultimately, we agreed on two promising approaches. The first involves using an atomizer driven by a microcontroller to disperse muscone throughout a space, allowing one or more users to alleviate IBD symptoms. The second approach suggests using a hydrogel that repeatedly absorbs and releases muscone solution, offering continuous delivery. When combined with a wristband or bracelet, this allows for on-the-go administration. In both cases, muscone can be dissolved in water or alcohol, providing a replenishable and long-term solution.
Who
Xu Youchun, an associate researcher at the School of Medicine, Tsinghua University.
Why
Xu Youchun has extensive experience in the precise manipulation of small samples and fluids, which is crucial for developing innovative solutions in medical and diagnostic fields. His research in microfluidic technology enables the precise control of fluids at very small scales, a skill that aligns perfectly with the challenges of delivering muscone in a controlled and efficient manner. Furthermore, his expertise in hardware design for medical devices, particularly in integrating multiple functions such as fluid control, temperature management, and signal detection into compact systems, provides an ideal foundation for advising on the technical aspects of our project.
Xu's familiarity with both the research and industrialization of biomedical technologies means that he understands not only the theoretical underpinnings but also the practical challenges of bringing a product to market. This dual perspective is invaluable for us as we aim to develop a system that is not only scientifically sound but also feasible for real-world applications. His proven ability to automate and miniaturize complex biochemical processes through engineering innovations suggests that he can offer practical advice on how to make our delivery mechanisms for muscone more efficient, reliable, and user-friendly.
Given his background in microfluidic technologies, Xu is likely to have deep insights into optimizing the design of our atomizer and hydrogel-based delivery systems, helping us to fine-tune the fluid mechanics and ensure that the muscone is dispensed at the correct concentration and rate. Additionally, his patent portfolio demonstrates a track record of solving complex technical problems through innovation, making him an ideal collaborator to help overcome any potential obstacles in our project.
Takeaway
During our academic exchange with PhD students from Dr. Zibo Chen's lab at Westlake University, we gained valuable insights into the forefront of synthetic biology. The focus was on learning how to construct intracellular circuit systems using proteins. These PhD students, who had participated in the iGEM competition during their undergraduate studies, provided us with guidance on our project, sharing their experiences and offering competition advice.
Who
PhD students specializing in synthetic biology at Westlake University.
Why
Traditionally, synthetic biology has concentrated on the modification and utilization of engineered microorganisms and their synthetic products. However, with advancements in biological technologies, scientists can now conduct more detailed research from a molecular perspective. We aimed to delve into the cutting edge of synthetic biology, hence we visited Westlake University for communication.
Dr. Zibo Chen's lab focuses on directly engineering proteins to create protein circuits. This approach, which combines computational biology and synthetic biology, aims to regulate biological metabolic processes and holds potential for treating human diseases. This innovative perspective provided us with new ideas on how to improve our project by focusing on the molecular intricacies of protein engineering.
Additionally, the PhD students, as former iGEM participants, shared their valuable competition experiences with us. They thoroughly reviewed our promotional materials and offered several suggestions to enhance our project.
Takeaway
In the Innovative Biology Laboratory of Shanghai University of Science and Technology, we exchanged views with the members of the Shanghai Tech 2023 and Shanghai Tech 2024 teams on the experience of team project design and team construction. We have learned the successful team building experience of the iGEM team of Shanghai University of Science and Technology, and reflected on our shortcomings in the team inheritance and construction.
Who
Shanghai Tech 2023 & Shanghai Tech 2024
Why
The iGEM team of Shanghai University has made excellent achievements in iGEM competitions in the past few years. In this discussion, we hoped to learn from the successful experience of iGEM team building of Shanghai University, especially in the successful experience of the team inheritance every year. At the same time, we could increase the cooperation channels between teams by expanding the communication with iGEM teams in universities in other cities.
In order to improve the efficiency of communication and increase the understanding of each other, our team members went to the Innovative Biology Laboratory of Shanghai University of Science and Technology to communicate with the Shanghai Tech 2023 and Shanghai Tech 2024 teams face to face. In this exchange, we increased the mutual understanding between the teams of the two schools, and introduced the stories behind the project presentation, which increased the understanding of each other's projects.
In the communication, we found that the iGEM team of Shanghai University of Science and Technology was closer and coherent each year. Every year, the new iGEMers will learn the experimental skills and rules of the competition under the leadership of the old iGEMers, which enables them to better learn the experience and lessons of the team each year, and improve the project design for the next year.
We hope that in the next year, we can learn from some advanced methods of the team of Shanghai University of Science and Technology, and further improve the inheritance between our teams every year. At the same time, through this exchange, we also hope to increase the communication with other iGEM teams, promote the cooperation between the teams, and jointly contribute to the application of synthetic biology.
Takeaway
In the conference room of the School of Bioengineering of East China University of Science and Technology, we communicated with the ECUST team members on the project design and the work of the two teams this year, enhanced the detailed understanding of each other's projects, and put forward some questions and improvement suggestions on each other's projects.
Who
ECUST team
Why
The ECUST team focused on disease prevention in aquaculture, and had conducted a wealth of research and practice in related fields.
In order to improve the efficiency of communication and enhance the understanding of each other, our team members went to the conference room of the School of Biological Engineering of East China University of Science and Technology to discuss with the ECUST team members offline. In this exchange, we fostered greater mutual comprehension between the teams from the two institutions, and shared the stories underpinning the project presentations, thereby enhancing the insight and familiarity with each other's projects.
During the exchange, the students of the two teams had an in-depth discussion on the progress of the project, design process, team building and other aspects, summarized some problems and solutions encountered in the wet experiment and dry experiment, and put forward some problems and suggestions on the project design and development of the experiment.
The ECUST team members put forward many effective suggestions on the colonization and quantitative measurement of our project, which was very helpful for our subsequent work. At the same time, we also hope to increase the communication and cooperation with other iGEM teams, collaboratively contributing to the advance and application of synthetic biology.
Takeaway
Initiated by Huazhong Agricultural University (HZAU-China), “Building the future with unity” 2024 iGEMer Central China Regional Exchange Conference is a large-scale, high-level and influential synthetic biology exchange meeting for college students in central China. It is an important platform for iGEM teams to communicate and learn from. During the conference, the team can show their project results, obtain professional guidance and evaluation, find partners and resources, improve their competitiveness and innovation ability. At the same time, the conference is also an important window in the field of synthetic biology in central China, where young students can understand the latest research dynamics and technological development, expand their vision and thinking, contact more opportunities and challenges, and promote the popularization and development of synthetic biology.
Who
Conference of central China iGEMer Community, consisting of 15 iGEM teams.
Why
Huazhong Agricultural University (HZAU-China) has excellent experience in iGEM competition and conference hosting level. This exchange meeting invited Tsinghua-iGEM to participate in the online to share the project, so it is a pity that we did not participate in the dinner party, games, laboratory visit and other rich activities organized by the sponsor.
In the meeting, we gained new knowledge and ideas from the wonderful reports of other teams. Some of the team's projects were related to us, and some teams encountered some questions similar to us. The judges gave profound questions and rigorous answers.
In our report, we expressed our gratitude for the invitation and the high quality of the conference. The guests asked us questions about the project design and the practical significance of the project, and helped us improve the project.
Takeaway
The Conference of China iGEMer Community (hereinafter referred to as CCiC) is a national conference independently initiated by China's iGEM participating teams. It aims to provide a platform for resource sharing for participating iGEM teams and young enthusiasts of synthetic biology in China, and to promote mutual learning and communication. Since its first holding in 2014, the CCiC conference has been the key focus of the CCiC Executive Committee's ongoing work to maintain the positive and vigorous development of the community, a national summit related to synthetic biology competitions in China, and an important academic communication platform for young enthusiasts of synthetic biology in China. We attended the CCiC th conference, where we shared our project, communicated with numerous teams, and sought collaboration opportunities.
Who
Conference of China iGEMer Community, consisting of 112 iGEM teams
Why
At present, the CCiC conference has become one of the largest academic conferences for college students in the country. At the conference, iGEM teams from all over China come together to exchange project designs and progress, engage in intellectual collisions, and receive targeted questions and suggestions from guests and judges. In addition, there are also exciting lectures brought by experts and scholars in the field of synthetic biology. CCiC 11th was held from July 11th to 14th in Xi'an Jiaotong-Liverpool University, Jiangsu Province of China. We took the chance to attend the conference and immersed ourselves in learning and sharing ideas within the realm of synthetic biology.
At the conference, we presented about our project, MusCure. We shared with everyone the basic concept, design approach, and advantages of MusCure over traditional therapies. At that time, our project was facing a tricky problem: how to successfully colonize our engineered bacteria in the gut. In communication with other teams, we discussed the feasibility and efficiency of using IBD-specific markers as molecular switches to trigger the expression of the ASL3 adhesion protein downstream. Thanks to the communication among our peers, our team ultimately decided to use the IBD-specific marker system as our colonization system.
At the conference, we also distributed the pamphlet we designed to many teams. Our pamphlet includes an overview of IBD, symptoms and causes of IBD, diagnosis and treatment of IBD, an introduction to synthetic biology, and our project MusCure. The pamphlet aims to raise public awareness of IBD and understanding of synthetic biology in a simple way. Our pamphlet is available in four languages: Chinese, English, French, and Arabic. Besides, to cater to the needs of special groups, we have also designed a large print version and an audiobook version.
Peering into the horizon, our optimism for CCiC knows no bounds. As we march forward, we're eager to witness the innovative ideas and projects that will spring forth, driven by the youthful enthusiasm and creativity of conference attendees. Furthermore, we're excited about fostering global collaboration and knowledge exchange, bridging borders to contribute to the worldwide advancement of synthetic biology in healthcare and other domains.
Takeaway
Tsinghua iGEMers is a big family. Collaborating with Tsinghua iGEMers improves our project's feasibility and social impact through insightful suggestions, and practical experiment guidance and experience sharing. This interdisciplinary and cross-grade collaboration enriches the project, facilitates innovation, and ensures its progress and success.
Who
Previous Tsinghua iGEMers and our team members
Why
The collaboration within Tsinghua iGEMers is essential. Only with the collaboration could we do problem-solving and ensure the novelty, feasibility, and applicability of our project.
Firstly, Tsinghua iGEMers guided our project ideas by offering inspiration and feedback. During our initial brainstorming sessions, each group had two seniors participating in the discussions to provide guidance. At the weekly full-group meetings, when we presented our brainstorming ideas, the senior students would listen attentively, offering affirmation and encouragement while also proposing practical suggestions. It was their feedback that stimulated our thinking, ensuring the rationality and feasibility at the early stages of our project.
Secondly, Tsinghua iGEMers provided us with guidance on experimental design, methodology, and scheduling. For instance, when we were designing the chimeric pathway, we sought advice from previous students who had worked on fusion proteins. In the initial stages of our experiments, when we were still unfamiliar with the procedures, such as performing ELISA, shaking cultures, or using ultrasonic crushers and microplate readers, it was the senior iGEMers who guided us through each step. In terms of scheduling, they also planned key milestones based on their experience, such as when to brainstorm, when to finalize the topic, and when to prepare for going abroad, ensuring that the project was completed on time and successfully.
Lastly, collaboration among Tsinghua iGEMers lit interdisciplinary sparks in our project. They came from diverse academic backgrounds, including biology, engineering, and medicine, possessing diverse areas of expertise and unique strengths, which led to a variety of perspectives, innovative thinking, and complement of skills. In a word, communication and collaboration within Tsinghua iGEMers is essential for the development and success of our project.
Takeaway
The team's visit to Bluepha, a company focusing on synthetic biology, facilitated industry connections and provides valuable insights from experts like Li Teng. They suggested that the muscone molecular switch can be used in large-scale microbiological industry, replacing the methyl alcohol promoter, and can improve the safety while lower the expense. Their advice indicated a wider prospect of industrial applications, which was quite inspiring for us. They also offered us practical opinions on research transformation.
Who
As a leading enterprise in China's synthetic biology field, Bluepha leverages synthetic biotechnology for molecular and material innovation. The company is dedicated to the design, development, manufacturing, and marketing of novel biomolecules and materials, which include biodegradable biopolymers like PHA that can spontaneously and completely degrade in all natural environments, functional beverage ingredients that effectively alleviate anxiety, novel functional probiotics that compensate for common metabolic deficiencies in the human body, as well as functional components for the beauty industry.
Why
Our team hoped to listen to the viewpoints of entrepreneurs and manufacturers representing the market to gain insights and collaboration in implementing our project. When searching for enterprises, Bluepha occurred to us. Bluepha is inextricably linked with iGEM and Tsinghua University. The co-founders, Li Teng and Zhang Haoqian, have both served as team leaders for Tsinghua University and Peking University respectively in the iGEM competition, leading their teams to gold medal victories. It was during these competitions that the two founders solidified their commitment to synthetic biology and jointly established the company. In its early days, Bluepha received incubation support from Tsinghua x-lab's Innovation Space and grew steadily. Moreover, Bluepha has also provided iGEM training through its "Bluepha Lab," accumulating rich experience in competition. Therefore, Bluepha would be a suitable choice for us, and we undertook the visit with the goal of bridging lab project and industry production.
We firstly took a tour in the company. In the research and development area of Blupha, we observed the costly array of fermentation tanks and the "dark lab," where we learned about the automated functions of the work platform, including pipetting, coating, and colony picking operations. These facilities enabled rapid strain screening, significantly enhancing the efficiency of R&D. The company also showcased the fermentation tanks used for scaled-up process experiments and the PHA raw material processing in the production workshop, demonstrating its wide application in areas such as flexible and rigid packaging, fibers, and agriculture, and providing users with detailed and comprehensive solutions. The digital platform and R&D system established and developed by Bluepha greatly accelerated product development speed. This platform was not only used for in-house research but would also be open and shared with aspiring tech innovation teams, aiding in overcoming challenges from concept validation to pilot testing. The incubation center reflected the responsibility of a leading enterprise in the field of synthetic biology.
During the exchange session, teachers with rich experience in the iGEM competition provided improvement suggestions for our project, helping us to expand the application scenarios of the project. We also discussed the current status and challenges of the industrialization of synthetic biology projects, sharing valuable experience ranging from market demands to strain selection. Specifically, they mentioned that the muscone molecular switch could be utilized to replace the methanol promoter in Pichia Pastoris for large-scale microbial industrial production, enhancing safety and reducing costs, which highlighted the promising application prospects of our modified elements. They also pointed out some of the difficulties in the transformation of scientific research. Currently, most of the industrialization in synthetic biology progresses from downstream market demands to upstream development, with strain selection based on these demands. Scientific research involving the modification of elements often struggles to find practical applications in production. We realized the importance of the two-way commitment between scientific research work and industrial production.
Our visit to Bluepha has proven to be an invaluable experience, allowing us to gain a deeper understanding of industrial production and project implementation within the synthetic biology field, and inspiring us of wider application scenarios. We are also eager to pursue further collaboration with the industry in the future.
Takeaway
A thorough understanding of clinical condition is vital for our engineering design. We acquired expert advice from the lecture of Dr Li Ji, a gastroenterologist in Peking Union Hospital. He comprehensively explained the classification, epidemiology, diagnosis, etiology and treatment of IBD. We focused on the current treatment, including their strengths and weaknesses, and analyzed the unique advantages of our cure.
Who
Li Ji, Deputy Director, Chief Physician and Master Supervisor of the Department of Gastroenterology, Peking Union Hospital. He specializes in the diagnosis and treatment of difficult and rare intestinal diseases such as inflammatory bowel disease, Cronkhite-Canada syndrome, hereditary gastrointestinal malformation polyposis, eosinophilic gastroenteritis, coeliac disease and autoimmune bowel disease.
Why
Before designing practical therapies for IBD, it is essential that we have a comprehensive understanding of the disease, encompassing both its pathophysiological mechanisms and the current status of clinical diagnosis and treatment. Information found online can be overwhelming, whereas reports from clinicians will be concise, comprehensive, and directly relevant to clinical practice. Therefore, we attended an authoritative report on IBD by Dr. Li from Peking Union Hospital.
Dr. Li began by explaining the definition and classification of IBD. Inflammatory Bowel Disease (IBD) is a group of non-specific inflammatory conditions of the intestines that are chronic and recurrent, and it can be categorized into Crohn's disease, ulcerative colitis, and indeterminate types. In China, there is a noticeable upward trend in the hospitalization rates for IBD. The pathogenesis of IBD is not yet fully understood but is influenced by genetic predisposition, environmental factors (such as infection, sanitation, and gut microbiota), and the body's immune response (such as disorders of the innate immune system). There is no gold standard for the diagnosis of IBD; however, it should be considered when symptoms such as mucusy blood-stained stools and recurrent abdominal pain are present. In terms of medication, the principle is to consider the course of the disease, the patient's age, previous treatment responses, and extraintestinal manifestations, among other factors, with the aim of achieving sustained mucosal healing without the use of steroids. Medications for treating IBD are classified into four major categories: aminosalicylates, corticosteroids, immunosuppressants, biologics and small molecule drugs, with biologics and small molecule drugs being more expensive and less accessible. At Peking Union Hospital, the treatment of IBD involves multiple departments, including outpatient services, endoscopy, and fecal microbiota transplantation, as well as the biologics.
Dr. Li's introduction provided us with an invaluable overview. We had a comprehensive and reliable understanding of IBD, which allowed us to design our project more targetedly. Moreover, the increasing trend of IBD patients in China, the challenges of recurrent and refractory IBD, and the high cost of biologic medications for IBD all underscored the necessity of our project.
Takeaway
Yeast therapy for IBD, while promising, poses clinical, safety, and ethical concerns. Expert advice from Dr. Li Yue emphasized effectiveness, safety and patient experience. She affirmed the increasing trend of IBD patients, with high morbidity in North America and Europe. She explained that the adverse effect of drug was related to the mechanism, and was unavoidable. As for innovative treatment, the butyric acid engineered bacteria and fecal transplantation had not been put into clinical use. In the discussion of patient experience, she mentioned some complications including enterostenosis, with high disability rate. Under her guidelines, we also recruited patients from student community and conducted interviews.
Who
Deputy Director of Education Division, Deputy Director of Clinical Postdoctoral Programme Office, Chief Physician, Professor and Postgraduate Supervisor of Peking Union Hospital. She specializes in clinical diagnosis and treatment of digestive diseases (gastrointestinal disorders, liver disease and pancreaticobiliary disease), experienced in immune-mediated gastrointestinal disorder and inflammatory bowel disease (IBD), and specializing in conducting endoscopy (gastroscopy, colonoscopy, magnifying chromoendoscopy, and enteroscopy).
Why
To gain a deeper understanding of the clinical situation and the feasibility of our therapy, we decided to engage in in-depth discussions with medical professionals. We got in contact with Dr Li Yue, who had extensive medical experience with IBD.
Dr. Li offered us precious advice. She suggested that we search for open-source databases on the gut microbiota and metabolic products of IBD patients to strengthen the evidence base for our project background. She clarified that adverse reactions were related to the drug's mechanism, not the method of administration. The efficacy of medications had its limits, with about 60% effectiveness, and all came with adverse reactions and limitations. The solution was to identify more therapeutic targets.
In terms of innovative therapies, butyric acid was known to be effective, but it was not used directly for treatment. There was literature on engineered bacteria that produce butyric acid, but it had not been successfully translated into clinical practice. Modulation of the gut microbiota, such as fecal microbiota transplantation (FMT), had not become a universally accepted treatment, although the higher the proportion of butyric acid-producing bacteria, the more effective the FMT seems to be, it had not been used clinically.
According to Dr Li, the incidence of IBD was on the rise, with high rates in Nordic and North American countries, and the number of patients in China was also increasing. Some patients were able to work normally, but others might suffer from severe complications with a high disability rate. If we intended to conduct human participant research, we would need to pass the ethical review of the hospital by submitting an ethical application. Dr. Li advised that we should avoid going through the hospital way if possible and conduct interviews within the university student population instead.
Dr. Li provided us with incisive insights into drug design and innovative therapies, and she guidelines led to the patient interviews later.
Takeaway
To get a deeper insight of clinical condition and drug design, we maintained a steady connection with Jiao Yuhao, a senior in Tsinghua School of Medicine and also a gastroenterologist in Peking Union Hospital now. He introduced the general treating methodology, the development of treatment and the corresponding efficacy. As for drug delivery, he explained the main challenges in oral administration and gave suggestions on improving the efficiency of gas delivery. He also provided guidelines on questionnaire design and patient interaction.
Who
Jiao Yuhao, Physician of Department of Gastroenterology, Peking Union Hospital.
Why
In the early stages of the project, after we had settled on the topic of IBD, we were eager to gain insights into the clinical aspects of IBD. However, it was not an easy task to obtain the contact information of medical professionals. Fortunately, one of our team members, who was a medical student, knew a senior, Jiao Yuhao, who had already started working at Peking Union Hospital. Consequently, we reached out to this senior for advice, inquiring about the clinical diagnosis and treatment of IBD, as well as his perspective on the design of our project.
We began by inquiring about the clinical treatment strategies for IBD. Jiao Yuhao explained that treatment strategies were quite complex, with different approaches for Crohn's disease and ulcerative colitis, as well as varying strategies for mild to moderate versus severe active conditions. However, the overall approach primarily involved the use of immunosuppressants/immunomodulators. Traditionally, the treatment core has been the use of intestinal-released salicylate preparations, with the consideration of adding corticosteroids based on the activity of the disease. Nowadays, there are new biologic agents available, such as infliximab, adalimumab, certolizumab, natalizumab, vedolizumab, and ustekinumab, each targeting different pathways. The efficacy in the era of biologics has improved, with an increased likelihood of maintaining disease inactivity or low activity, by about 20%. We also asked about the feasibility of inhalational delivery, to which Jiao Yuhao advised us to calculate the distribution gas volume and assess the dose required to reach therapeutic concentrations. While offering us warm advice, Jiao Yuhao also expressed his full support for our project and offered to help us find patients.
Later on, we sought to demonstrate the advantages of inhalational therapy over oral administration. Since our senior Jiao Yuhao had told us to contact him any time we had questions, we consulted him again when considering the disadvantages of oral medications. Jiao Yuhao mentioned that in principle, drugs could be administered orally with the addition of appropriate adjuvants and controlled-release systems, but oral delivery was still subject to limitations such as the first-pass effect, bioavailability, and toxicity of metabolites. We also took into account that oral administration could be relatively less convenient. Inhalational therapy, on the other hand, retained its unique advantages.
When we were planning to conduct a patient survey, we also consulted Jiao Yuhao about ethical and legal matters. We wanted to know if surveying patients for their opinions required policy review. Jiao Yuhao informed us that survey questionnaires typically needed to include a privacy and confidentiality agreement, which we should place at the beginning of our questionnaire.
We are extremely grateful for Jiao Yuhao's ongoing support and advice. Reliably and heartily, he provided us with a primary understanding of IBD, explained pharmacological knowledge related to our project, and guided us through our clinical investigation.
Takeaway
Li Jingwen, a senior in Tsinghua School of Medicine, also working in microbiome lab, highlighted the challenges in yeast colonization and feedback acquisition, which was thought-provoking and inspired us to improve our project. She also discussed the relatively low efficacy of fecal microbiota transplantation, and stated that IBD was a recurrent disease with no cure. Therefore, it is of great significance to find a long-term, convenient and patient-friendly alleviation.
Who
Li Jingwen, undergraduate student at School of Medicine, Tsinghua University.
Why
Early in our project, we aimed to reach out broadly to people with clinical experience in IBD to provide more background for our project and to exchange ideas about our topic. One of our team members, a medical student, inquired in her department's alumni WeChat group if any senior alumni were working in gastroenterology. A senior alumnus got in touch with her. Although she herself was not in the gastroenterology department, her mother was working in the gastroenterology department at Peking University Hospital, and her future research direction was related to IBD. She expressed interest in engaging in a discussion with us.
Before we had introduced ourselves, she had methodically inquired about our project in detail, including the action mechanism and regulatory mechanism. She also pointed out some of the challenges our project might face, such as how the yeast would colonize, how to monitor population density and the yield, and how to obtain feedback from the control system, which profoundly stimulated our thinking. Following this, she discussed the current clinical status of IBD treatment, which mainly involved anti-inflammatory immunotherapy. Her research focus was on fecal microbiota transplantation, which only elicited a response in about one-third of the patients. She highlighted that the hallmark of IBD was its recurrent nature, and there was no guaranteed cure. Therefore, long-term relief with a good patient experience could be a viable solution. Finally, she reminded us that if there were complex control mechanisms in the yeast, colonization would be the biggest challenge, and we would need to prevent the yeast from being crowded out by the existing intestine flora. This advice was very pertinent and prompted us to start considering methods of colonization.
Since Li Jingwen's own research was in the field of IBD, the advice she provided was incisively to the point. Communicating with her was highly enlightening for us and prompted us to begin contemplating and attempting to address the challenges associated with the clinical translation of our project.
Takeaway
Since the experience of patients is the core of a human-centered therapy design, we recruited and interviewed student patients from various regions in the world. They elaborated the everyday feelings of IBD patients and expressed their wholehearted support for our project, which was encouraging. They also provided valuable suggestions on product design to ensure convenience.
Who
IBD patients.
Why
Medicine revolves around the human core. Our therapy is designed for IBD patients and must necessarily incorporate the opinions of the patients and align with their needs. Due to the particularity of IBD conditions and the confidentiality required for patient interviews, we faced numerous obstacles in reaching out to patients. However, we still managed to interview four patients, one of whom chose to remain anonymous, while the other three were willing to appear on camera. We introduced our therapy to them and listened to their perspectives.
During the interview, we began by introducing ourselves, explaining the purpose of the interview, and ensuring that the patient was fully informed. Subsequently, we inquired about the patient's medical history, such as whether they were suffering from Crohn's disease or ulcerative colitis, the symptoms they typically experienced, the current treatment they were undergoing, as well as its efficacy and side effects. We paid particular attention to the impact of IBD on the patient's daily life, including whether it affected their work, study, social activities, and mental health. Following this, we introduced our Muscure therapy, detailing the administration method and the principle behind the treatment. We asked the patients if they had any suggestions for improving our treatment approach and what their greatest expectations were for the outcomes of our project. Given that our therapy was more convenient and had fewer side effects compared to traditional treatments, we were also interested in whether patients would be inclined towards our inhalational treatment. In the end, we summarized the key points of the interview and expressed our gratitude.
The patients have put forward many enlightening perspectives. For instance, they suggested that making the product in the form of a bracelet or necklace could be more convenient to carry than a medicine sachet. Additionally, on the other hand, their trust in traditional Chinese medicine could enhance the credibility of the sachet in their eyes. Moreover, some patients have expressed their anticipation for the launch of our product and have even volunteered to be testers. Although the actual launch requires rigorous clinical trials, we are deeply moved by the patients' expectations and trust, which also fuels our motivation for research and innovation.
Through interviews with IBD patients, we gained insights into their conditions, treatment histories, and the impact on their daily lives. We delved into their expectations regarding the muscone therapy, thereby clarifying the potential significance and areas for improvement of the project.
Takeaway
We had online meetings with Codemao company and consulted how to design a popular science programming software with synthetic biology background to better popularize the principles and concepts of synthetic biology among teenagers.
Who
Codemao company is an educational technology company focusing on youth coding education, founded in March 2015, dedicated to providing innovative programming learning experience for teenagers aged 4-16.
Why
The concept and principle of synthetic biology for teenagers is too abstract to understand. We hope to analogy the principle of modular programming, putting the biological components in synthetic biology into similar blocks and designing a similar modular programming software, to help teenagers understand the principle and concept of synthetic biology, and make synthetic biology better popular in the adolescent group.
Codemao company is a representative enterprise of youth programming education in China, and its success has promoted the popularization of programming technology among young people. We hope that this exchange will transform our vision of modular programming software for synthetic biology into a specific design and get more advice on software development.
In the discussion, Codemao company fully affirmed our vision for the development of modular science software for synthetic biology, and provided us with many basic tools for the development of modular programming software to further implement our ideas.
Through this exchange, we have had a more detailed design scheme for the idea of synthetic biology popular science software. At the same time, we hope to carry out cross-field cooperation with more enterprises in different fields to carry out more cross-cutting projects related to synthetic biology and promote the wider popularization of synthetic biology in more fields.
Takeaway
Our team had produced a project promotional brochure, and for user-friendly, we were planning to design a large-print edition based on the standard brochure. We consulted Bao Guohong from the Braille Press to understand the standards for large-print manuals and to have her viewpoints on what adjustments we should make. Bao Guohong provided some revision suggestions from the perspective of visual disability, and we created a version of the manual tailored for visually impaired people.
Who
Baoguohong, the editor-in-chief of the China Braille Press.
Why
We had created an informational booklet to promote our project. In order to enhance the attention given to minority groups, we planned to design a large-print edition. Due to our lack of experience in this area, we sought advice from Bao Guohong, the chief editor of the China Braille Press. We sent her our booklet and asked for her advice.
Regarding our primary concerns, Bao Guohong stated that the minimum font size for large-print materials should be 3 points. In terms of typography, it was advisable to avoid using script or cursive fonts, and the line color should be intensified. There should be a clear contrast between the text and the background color; for instance, red text should not be placed on a red background. Specifically, she highlighted areas in our booklet that required improvement, such as changing the text color to blue-purple or dark green, using pure colors for the background, avoiding black backgrounds and ornate fonts, among other suggestions. Additionally, she made recommendations on font selection. As for images, individuals with low vision could see them, but it required more effort. It was preferable to avoid using gradient colors in images. If the image was the main content, it was important to emphasize the colors of the image and either remove or diminish colors that might cause distraction.
Bao Guohong's professional and practical advice was incredibly helpful. Following her suggestions, we refined our science promotional brochure and created a version for the visually impaired, expanding our target audience.