Overview

Our approach to Human Practices was not a parallel track but the central nervous system of our project, HpBuster. We operated on a core philosophy of holistic integration and bidirectional dialogue, guided by a dynamic and purpose-driven methodology. This meant iHP was a continuous process woven into every stage of our work, where the needs of the world actively shaped our project, and in turn, our project sought to contribute meaningfully back to the world.

The strength of our iHP was its broad and authentic stakeholder engagement. We interviewed H. pylori patients and consulted with clinicians to understand the real-world challenges of antibiotic resistance. Our scientific direction was guided by 12 academic experts, while over 20 industry pioneers from 12 companies informed our path from lab to market. Finally, we fostered deep, one-on-one exchanges with 8 iGEM teams, part of our broader dialogue with dozens in the community.

Our iHP architecture was designed to mirror the project’s lifecycle and its two-way dialogue with the world. It began with “Origin & Mission,” where our engagement with patients, the public, and clinicians anchored our work to a genuine societal need. This led to the core of our process, “Feedback-Driven Engineering,” a continuous loop where external insights actively refined every aspect of our project, including the core system’s design, our safety framework, public communication strategy, and future entrepreneurial vision. Finally, our project radiated influence outwards through “Scientific Community Outreach,” where we contributed our findings and platforms back to the broader scientific community.

Figure 1: An overview of our integrated human practice framework.

Part 1 - Origin & Mission: From Societal Needs to Project Mission

Our project, HpBuster, originated in the spring of 2025 from two initially unrelated ideas: one aimed to regulate microbial community dynamics by disrupting inter-population communication, and the other sought to use live therapeutics for treating gastrointestinal infections. The merger of these concepts during a brainstorming session led us to a new strategy—clearing pathogens by interfering with their interactions. We preliminarily selected Helicobacter pylori (H. pylori) as our target due to its widespread impact and the known challenges of existing treatments.

However, a promising idea born in the lab is only the first step. To transform this initial concept into a truly meaningful project, we needed to answer a profound question: “Why is our work truly important?” To find the answer, we turned our gaze beyond the laboratory to the real world, systematically listening to the voices of patients, the public, and frontline clinicians. This series of investigations was designed to validate our direction and, more importantly, to allow real-world needs to shape our mission and technical design from the very beginning.

Listening to Patients: Voices of Pain and Hope

To deeply understand the real experiences and unmet needs of individuals with H. pylori infection throughout the entire process of diagnosis, treatment, and recovery, we conducted in-depth interviews with patients of different ages and varying symptoms. These conversations revealed a reality full of contradictions: whether the infection was symptomatic or silent, existing therapies brought distress to patients in various ways.

A young patient’s experience was both painful and profound. After being infected with H. pylori, he suffered from frequent burping and gastroenteritis for a long time; any raw, cold, or greasy food would trigger discomfort. This not only severely affected his daily diet and quality of life, but the recurring illness also led to physical weakness, disrupting his normal work and life. While undergoing “quadruple therapy,” he experienced severe side effects, including a high fever of 38°C after taking one of the antibiotics (minocycline hydrochloride), which forced him to switch medications mid-treatment. He painfully recalled that while the potent antibiotics eradicated H. pylori, they also destroyed his normal gut flora, leading to prolonged gastrointestinal dysfunction afterward.

The experience of another middle-aged patient represents a different demographic. He discovered his infection incidentally during a routine company health check-up and had no obvious symptoms. Although he did not feel strong side effects during his triple therapy, he clearly understood that “taking antibiotics is bad for the body and can also lead to drug resistance”. He stated that because H. pylori infection is not an acute emergency, he would be very willing to try a new, safer probiotic therapy with fewer side effects.

These two distinct experiences point to a clear clinical pain point: The current antibiotic-centered eradication regimens, while effective, come at a heavy cost. For symptomatic patients, the treatment process can be accompanied by severe adverse reactions that seriously impact their quality of life. For asymptomatic carriers, concerns about the “all medicines have side effects” principle and antibiotic resistance make them eager for gentler treatment options. These direct voices from patients have solidified our belief that developing a “living drug” capable of precise targeting, avoiding side effects, and protecting the intestinal microecology is an urgent task to meet the real needs of patients.

Figure 2: Conducting an in-depth interview with a patient to understand the real-world challenges of H. pylori infection and treatment.

Understanding Public Perception: A Mandate from Survey Data

To understand public perspectives on H. pylori, we conducted a survey collecting 487 valid responses. The analysis reveals a clear need for improved treatment options, validating our project’s direction.

Public Cognition: A Mix of Awareness and Misconception

Public knowledge of H. pylori is moderate. Over 70% of respondents rated their own understanding as “average” or lower. While a majority (85.22%) correctly identified oral-oral transmission, significant misconceptions persist, with many incorrectly believing it spreads through respiratory (36.96%) or blood-based (16.22%) routes. This knowledge gap exists despite high awareness of its primary danger, as over 83% knew of its link to gastric cancer. This shows that while people recognize the threat, they lack precise knowledge for prevention, highlighting a need for public education.

Figure 3: Survey data on public understanding of H. pylori transmission routes, revealing a mixture of correct knowledge and common misconceptions.

Current Treatment: Effective but Burdensome

Among respondents with a history of infection, 77.08% had received the standard “quadruple therapy.” Although over 75% found it effective, the treatment experience was poor. Over 66% of patients suffered from side effects, most commonly gastrointestinal discomfort (24.32%) and oral odor (20.27%). When asked what needed improvement, patients ranked “long treatment duration” and “high drug load” as their top concerns, followed by “severe side effects” and “high recurrence rate.”

Figure 4:The prevalence of side effects experienced by patients during standard antibiotic therapy for H. pylori.

Figure 5: Patient-reported aspects of current *H. pylori* treatments most in need of improvement, with treatment duration and drug load being the top concerns.

Public Expectations: High Demand for Novel Therapies

The shortcomings of current treatments have created a strong public desire for better alternatives. Our proposed “engineered probiotic therapy” was met with overwhelming enthusiasm, as 82.29% of respondents were willing to try it. The most influential factors driving this acceptance were “efficacy” and “safety/side effects,” which ranked far above “cost”.

Figure 6: Public willingness to try a novel engineered probiotic therapy, showing high acceptance among survey respondents.

Figure 7: Key factors influencing patient decisions to adopt a new therapy, with efficacy and safety being the most important.

These results send a clear message: patients seek a high-quality treatment experience, not just an effective one. The core demands are fewer side effects, a simpler regimen, and a lower recurrence risk. The public’s high acceptance of a novel probiotic solution provides a strong mandate for our project.

Consulting with Clinicians: Expert Insights on a Global Challenge

To validate our project from the strategic perspectives of clinical medicine and public health, we conducted an in-depth interview with M.D. Zhanlong Shen, a leading gastroenterology expert. His insights confirmed our earlier findings from patients and the public, and elevated our project’s significance to addressing a global health challenge.

Figure 8: A strategic synthesis of our dialogue with Dr. Zhanlong Shen, highlighting the clinical bottleneck of antibiotic resistance and validating our proposed solution.

Dr. Shen identified the “most central and urgent bottleneck” in current H. pylori treatment as severe antibiotic resistance, which has led to a significant decline in eradication rates. He also highlighted that treatment side effects are a major clinical challenge, causing approximately 20% of patients to discontinue medication early and contributing to treatment failure.

Crucially, when discussing future trends, Dr. Shen endorsed “adding specific probiotics as an adjuvant therapy” to increase efficacy and alleviate side effects. This provides a strong clinical and authoritative validation for our core approach of using an engineered probiotic as a novel therapeutic agent.

Chapter Summary:

By integrating the urgent needs of patients, the general expectations of the public, and the profound insights of clinical experts, we have distilled the core mission of our project: to create a novel “living drug” based on engineered probiotics to tackle the severe challenge of antibiotic resistance and provide a highly effective, safe, and low-side-effect treatment option for the hundreds of millions of people infected with H. pylori worldwide. This is not a minor improvement on existing therapies but a bold exploration aimed at reshaping the treatment paradigm. These voices from the real world are the foundation and starting point of all our work.

Part 2 - Core System Refinement: From Blueprint to Breakthrough

As a central component of our broader Human Practices efforts, this section, “Core System Refinement,” details the engine room of our project’s technical development. While other parts of our iHP address our mission, safety, and public engagement, our focus here is on the direct, iterative loop connecting expert consultation with tangible laboratory progress. Our objective is to demonstrate how we systematically translated dialogue into data, refining our project’s foundational modules—Adhesion, Sensory & Therapeutic, and Delivery—through a structured cycle of feedback and implementation.

Figure 9: Our DCRI (Design-Consult-Refine-Inplement) Strategy.

The methodology governing this refinement process is our Feedback-Driven Engineering Loop (DCRI). Each engineering challenge began with an initial Design, which we then critically evaluated by Consulting academic and industrial experts. Their insights empowered us to Refine our strategies—identifying potential flaws and optimizing our approach—before committing to lab work. Finally, we would Implement these improved designs through rigorous experimentation, with the results informing the next cycle of innovation.

The following case studies showcase this engineering-focused dialogue in action. By embedding this feedback loop into our R&D, we ensured that the foundational science of our project was not only ambitious but also practical, safe, and strategically sound, providing a solid technical base for the broader goals of our entire iHP endeavor.

Adhesion Strategy: From Delayed to “Always-Ready” Adhesion

Overview

To maximize therapeutic efficacy, our engineered yeast must not only sense and act, but first and foremost, remain anchored at the site of infection. The design of our Adhesion System, therefore, represented one of our earliest and most fundamental strategic challenges. This section details the foundational pivot we made in response to expert feedback, a critical decision that shaped the architecture of our entire project. We began with a concept where adhesion was inducible, triggered only upon sensing H. pylori. However, early consultations challenged this idea, raising concerns about metabolic load and a critical time-lag that could render our system ineffective in the dynamic gastric environment. This led us to re-evaluate and ultimately adopt a more robust constitutive expression strategy, ensuring our yeast is always ready to bind its target.

Consultation: Re-evaluating the Adhesion Strategy with Prof. Qingsong Wang and Dr. Long Qian

Date: March 9, 2025

Experts:

• Prof. Qingsong Wang, Associate Professor, School of Life Sciences, Peking University
• Dr. Long Qian, Associate Investigator, Center for Quantitative Biology, Peking University

Background & Purpose:

Our initial design aimed to link the adhesion system directly to the sensing system. The yeast was engineered to first detect Nα-methylhistamine, a signal molecule unique to H. pylori, and subsequently trigger the expression of the C1ND adhesion domain on its surface. This approach was conceived to conserve the yeast’s metabolic energy, ensuring that the adhesion proteins were only produced when the target pathogen was present. The purpose of our consultation during this early brainstorming stage was to present this concept to Professor Qingsong Wang and Dr. Long Qian. We aimed to leverage their expertise in biochemistry and computational synthetic biology to discuss the design’s feasibility and gather critical feedback before proceeding.

Insights from the Conversation:

Both experts provided critical feedback that challenged our initial assumptions. They raised two primary concerns:

1. Plasmid Metabolic Load: They pointed out that integrating a complex inducible system, which includes both sensing and adhesion components, onto a single plasmid would create a significant metabolic burden for the yeast cells. This high plasmid load could negatively impact the yeast’s growth, stability, and overall therapeutic function.
2. Sensing Delay Effect: he experts highlighted the critical issue of a “time-lag.” The process—from detecting the signal molecule to transcribing the gene, translating the C1ND protein, and successfully displaying it on the cell surface—would not be instantaneous. They argued that this delay could significantly reduce the system’s effectiveness; the yeast might flow past the infection site in the stomach before it could firmly attach.

Action & Outcome:

Based on this crucial expert feedback, we made a pivotal change to our project design. We decided to decouple the adhesion system from the sensing system. The gene encoding the C1ND adhesion domain was placed under the control of a strong constitutive promoter, ensuring it is always expressed on the yeast surface.

This strategic shift simplified the genetic circuit, reduced the metabolic load on the host, and critically, eliminated the risk of the time-lag effect. Our engineered yeast is now “always ready” to bind to H. pylori upon encounter, ensuring immediate and efficient localization at the infection site. This early consultation was fundamental in shaping a more reliable and effective design for our adhesion system.

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Delivery System: Forging the “Landing Craft”

Overview

With a robust strategy in place to ensure our yeast remains anchored to H. pylori, our next critical challenge was to engineer its core function: the ability to sense the pathogen and deliver a targeted therapeutic response. This section details the iterative refinement of this crucial system, which underwent a fundamental redesign catalyzed by expert consultations. Our initial path, based on a split-ubiquitin nanobody system, was fraught with potential obstacles. Through dialogue with experts in microbial engineering and synthetic biology, we pivoted to a more viable and innovative GPCR-based sensing mechanism, systematically optimized our genetic pathways, and established rigorous validation protocols, forging a clear and scientifically sound path forward.

Consultation 1: Pivoting Our Sensing Strategy with Dr. Long Hong

Date: July 10, 2025

Expert: Dr. Long Hong, School of Life Sciences, Peking University

Background & Purpose:

Our initial design for the sensory module was based on a split-ubiquitin nanobody system intended to recognize surface antigens on H. pylori. However, we quickly ran into a wall of potential obstacles. We were concerned about steric hindrance from the yeast cell wall, as well as the system’s potential instability and inefficient signal transduction within a complex in vivo environment. To find a more viable path forward, we consulted Dr. Long Hong, an expert in microbial engineering and protein display technology, to discuss a fundamental shift in our approach: moving from nanobodies to a GPCR-based system.

Insights from the Conversation:

Dr. Hong, a distinguished researcher in microbiology and protein engineering, immediately validated our concerns. He pointed out that the dense yeast cell wall would likely prevent a nanobody from effectively binding to the pathogen. Drawing from “yeast display” technology, he suggested methods for localizing membrane proteins to the cell surface to overcome this spatial barrier.

This insight prompted us to propose a new idea: what if, instead of recognizing a surface antigen, we detected a metabolic byproduct of H. pylori, such as histamine, using a GPCR? Dr. Hong confirmed this was a highly promising direction. He further enriched our strategy by suggesting we could adapt secretion systems from E. coli, which use signal peptides like MBP, for our therapeutic protein. He advised us to research secretion signal sequences native to our chassis, S. boulardii. Beyond the core biology, Dr. Hong also offered practical advice on downstream technologies like microcapsule preparation and even offered to help us access key instrumental resources.

Action & Outcome:

This interview was the turning point for our sensory module. Guided by Dr. Hong’s expert advice, we made the decisive choice to abandon the nanobody approach and commit fully to a GPCR-based metabolite-sensing pathway. We immediately began a deep dive into the literature, screening for suitable GPCRs, optimizing signal peptides, and designing our yeast surface display system. Dr. Hong’s insights and generous offer of support dramatically accelerated our project’s redesign, laying a robust foundation for all subsequent work.

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Consultation 2: Technical Deep Dive on GPCR Engineering with Bohan Li

Date: July 3, 2025

Expert: Bohan Li, Graduate Student, Yulong Li Lab, Peking University

Background & Purpose:

As we moved forward with our GPCR strategy, we encountered a new set of technical bottlenecks, specifically in the construction of chimeric G-proteins. We needed to know how to rationally select G-protein alpha-subunits for combinatorial screening, understand the precise molecular cloning details, and get an expert opinion on the overall feasibility of our plan. These details were critical for the functional implementation of our sensory module. We sought the expertise of Bohan Li, a senior graduate student in the renowned Yulong Li Lab at Peking University, to guide us through these technical nuances.

Insights from the Conversation:

Bohan Li provided clear, actionable guidance that transformed our abstract plan into an executable roadmap. He recommended a systematic screening of combinations between histamine receptors and G-protein families and illuminated the standard method for constructing chimeric G-proteins by replacing the C-terminal 5-11 amino acids. He also clarified a key detail in our expression strategy: the GPCR requires a signal peptide for proper membrane insertion, but the G-protein itself does not. His advice provided the technical clarity we desperately needed to move forward efficiently.

Action & Outcome:

Armed with Bohan Li’s advice, we completely overhauled our experimental plan, transforming it from a concept into a highly efficient workflow. We designed a systematic screening protocol, established a small-scale chimeric G-protein library, and perfected our molecular cloning strategy. These targeted improvements unlocked our progress, making our project far more executable and dramatically increasing our R&D efficiency.

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Consultation 3: Ensuring Safety and Rigor with Associate Professor Zhexian Tian

Date: August 14, 2025

Expert: Prof. Zhexian Tian, Peking University

Background & Purpose:

As we developed our therapeutic module, we faced critical questions not just of efficacy, but of scientific integrity and responsibility. We were unsure about the specific safety protocols for culturing Pseudomonas aeruginosa and needed to establish a reliable, gold-standard method for quantifying biofilm. Furthermore, we had to critically evaluate the real-world feasibility of our therapeutic enzyme, AiiA. To ensure our project was built on a foundation of safety and scientific validity, we consulted microbiology expert Prof. Zhexian Tian.

Insights from the Conversation:

Prof. Tian began by instilling in us the paramount importance of laboratory safety. On the technical side, he recommended crystal violet staining followed by a plate reader assay as the definitive method for biofilm quantification. Regarding our AiiA enzyme, Prof. Tian offered a crucial molecular perspective: because AiiA targets the highly conserved quorum sensing system, the risk of developing resistance is relatively low. This insight provided critical validation for our therapeutic approach, but he stressed the importance of experimentally validating its degradation efficiency.

Action & Outcome:

Following Prof. Tian’s guidance, we immediately embedded a new layer of rigor and safety into our project’s DNA. We established a standardized and normalized workflow for biofilm quantification and designed a comprehensive suite of experiments to systematically evaluate our AiiA enzyme. Prof. Tian’s mentorship did more than refine our methods; it ensured the successful and responsible execution of our project, reinforcing the core principles of sound science.

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Sensory & Therapeutic System: Building the “Smart Missile”

Overview

Having engineered a yeast capable of both adhering to and acting upon its target, the final piece of our technical puzzle was ensuring it could survive the journey through the harsh gastrointestinal tract to reach the site of infection. This section chronicles the development of a robust delivery system, a journey that evolved from a simple encapsulation concept to an advanced, integrated microfluidics platform. We faced significant technical hurdles, including the structural collapse of our microbeads and critical safety constraints related to propulsion materials. Through targeted consultations with academic and industrial experts, we systematically navigated these challenges, demonstrating an iterative design process that transformed our delivery vehicle into a precise, scalable, and innovative solution.

Consultation 1: Refining Encapsulation Strategy with Dr. Long Hong

Date: July 10, 2025

Expert: Dr. Long Hong, School of Life Sciences, Peking University

Background & Purpose:

Our initial plan for creating microbeads to encapsulate our yeast cells was based on the emulsification–internal gelation method for producing sodium alginate beads. This method was conceptually feasible and well-supported by existing literature, offering the advantage of lower equipment requirements. However, our team identified potential concerns regarding the control of particle size and the overall reproducibility of the process. We understood that significant variations in bead size could impact the consistency and reliability of subsequent experiments. In contrast, microfluidic systems were known to offer superior control and uniformity, but at the cost of higher technical complexity. To determine the most effective path forward, we consulted Dr. Long Hong, leveraging his experience with alginate gel systems and cell immobilization techniques to help us weigh the trade-offs between these two methods.

Insights from the Conversation:

Dr. Hong provided a clear assessment of our options. He affirmed the distinct advantage of microfluidic systems for achieving uniform particle size, a critical factor for precision applications. However, he also acknowledged the technical challenges and steeper learning curve associated with implementing such systems. Dr. Hong advised that the emulsification–internal gelation method was a reasonable and practical starting point for our project. He reasoned that if our initial application phase did not demand extreme precision, this simpler method would be sufficient to produce the necessary materials for proof-of-concept experiments, allowing us to make progress without being delayed by complex technical optimizations.

Action & Outcome:

Based on Dr. Hong’s input, we adopted a phased strategic approach. We decided to begin our experimental work using the simpler emulsification method. This allowed us to initiate our proof-of-concept studies promptly, utilizing accessible resources and techniques. In parallel, we designated microfluidics as a long-term optimization pathway for our delivery system. This decision enabled us to proceed efficiently with our biological validation work while simultaneously conducting the necessary research and design for a more advanced fabrication method. This approach retained the potential for future scalability and precision while ensuring immediate progress.

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Consultation 2: Addressing Magnesium Coating with Prof. Qing Chen

Consultation 3: Exploring Industrial Feasibility and Safety Constraints

Date: July 2025

Partners Contacted: Hangzhou Furui Jie Technology co., LTD, Engineering For Life (EFL), Beidi Technology co. LTD, BMF Precision Tech, Guangdong Institute of Semiconductor Micro-Nano Manufacturing Technology, Quantum Design China, Nanjing Nanoeast Biotech co., LTD, Thencure co., LTD

Background & Purpose:

As our project progressed, two significant practical issues emerged that required an industrial perspective. The first was the recurring collapse of our alginate beads during the freeze-drying process. The second, more critical issue concerned the regulatory and safety restrictions on the use of magnesium nano-powder, which we had learned posed potential explosion risks. To evaluate viable solutions and understand the real-world constraints, we reached out to several industrial companies with expertise in materials, biotechnology, and equipment manufacturing.

Insights from the Exchanges:

The feedback from our industrial partners was invaluable. Regarding the freeze-drying issue, experts confirmed that advanced equipment and specialized protective agents were available and could likely solve the bead collapse problem, but they also cautioned that the necessary process optimization would be both complex and time-consuming. The feedback on magnesium nano-powder was definitive: all companies emphasized the strict safety regulations governing its use. They confirmed that its application would require anti-explosion certification, a significant regulatory hurdle that would severely limit the feasibility of our approach, particularly for future clinical or commercial development.

Action & Outcome:

These discussions directly influenced a major strategic decision. Based on the clear safety and regulatory feedback, we decided to deprioritize approaches involving magnesium nano-powder. We shifted our focus to developing safer, more scalable alternatives, such as using bulk magnesium powder or biocompatible inorganic substitutes that would not carry the same risks. This early engagement with industry allowed us to align our project with practical constraints, preventing us from investing further resources into a technologically and regulatorily challenging path.

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Consultation 4: Overcoming Freeze-Drying Challenges with Prof. Xuan Zhang

Consultation 5: Developing an Integrated Janus Micromotor System

Date: August 4 & August 10, 2025

Expert: Dr. Shujing Wang, Microfluidics Fabrication Platform, Peking University; Engineers at Dxfluidics Ltd.

Background & Purpose:

To overcome the limitations of a multi-step fabrication process and to integrate the encapsulation and propulsion functions more effectively, we advanced our design to a microfluidics-based system for fabricating Janus particles. The design consisted of a single particle with two distinct hemispheres: one made of alginate hydrogel for encapsulating the yeast, and the other made of calcium carbonate (CaCO₃), which would function as a safe and biocompatible micromotor. This integrated approach required expertise in microfluidic device design and fabrication.

Insights from the Conversations:

Our development of this system was a collaborative effort. Dr. Shujing Wang, an expert at the Peking University Microfluidics Fabrication Platform, confirmed the feasibility of our proposed design. She provided a key technical suggestion to optimize the oil phase in the microfluidic device by using soybean oil with 1% Span-60, which she advised would improve the stability and uniformity of droplet formation. We also collaborated with engineers at Dxfluidics Ltd. Working together and referencing relevant literature, we jointly designed custom microfluidic chips that were then manufactured by the company to meet our specific experimental requirements.

Action & Outcome:

With the combined support of academic expertise and industrial manufacturing capabilities, we successfully designed and partially validated a reliable microfluidics-based method for producing Janus particles. This advanced solution ingeniously integrates encapsulation and micromotor propulsion functions into a unified entity. The development of this platform effectively overcomes previous challenges of particle collapse and magnesium safety, while providing our project with a precise, scalable, and innovative delivery system.

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Part 3 - Safety Framework Construction: From Precaution to Contribution

For any project involving the release of a genetically modified organism, safety is not merely a component; it is the foundational bedrock. From the outset, we built our project upon a robust framework of safety, evolving our understanding and practices through a three-stage process: learning from foundational principles, designing rigorous validation, and contributing our findings back to the community.

Figure 10: The three-stage evolution of our safety framework.

Initiation: Learning from Experts and Peers

Our safety journey began by internalizing foundational warnings. Dr. Shen Zhanlong, a gastroenterology expert we interviewed, cautioned us about the systemic risks of introducing a genetically modified microorganism (GMM), specifically highlighting horizontal gene transfer, disruption of native gut microbiota, and environmental spread. This expert advice established a high bar for our project’s safety from day one.

We then turned to our peers to understand the state-of-the-art in safety design. At the Live Biotherapeutics Exchange Meeting we hosted, we were profoundly inspired by the innovative safety architectures presented. While team TJUSX showcased robust multiple “kill switches,” it was iZJU-China’s DNA origami-based CRISPR delivery system that represented a paradigm shift for us. Their design, which physically separates therapeutic function from replication, demonstrated a proactive philosophy of “Safety by Design” rather than merely reactive containment. This concept became a core tenet of our thinking. Subsequently, during the CCiC poster session, persistent questions from judges and peers about our project’s long-term ecological impact acted as the final catalyst, pushing us to translate theoretical understanding into a concrete validation plan.

Figure 11-13: The initiation of our safety framework, sparked by foundational expert advice (top) and catalyzed by critical questions from peers and judges at the Live Biotherapeutics Exchange Meeting (bottom left) and CCiC (bottom right).

Development: Designing a Rigorous Experimental Framework

The pressing questions from the community created a clear directive: we needed a robust method to assess our engineered yeast’s ecological impact. Experts at BGI confirmed this urgency, noting that effective colonization would likely require continuous administration, making its long-term effects a critical question. With a well-defined problem, we sought a methodological solution from the team at Xbiome. They provided the crucial missing piece: a powerful suggestion to use a metagenomic method like the micro-method (mipro) to assess the impact by stably passaging fecal samples.

Figure 14-15: Our visits to BGI (left) and Xbiome (right), where we received critical expert advice that shaped the design of our comprehensive ecological safety assessment protocol.

This actionable advice allowed us to design a comprehensive experimental protocol to co-culture our engineered yeast with fecal microbiota. The plan included a multi-dimensional analysis, featuring metagenomic sequencing to track community structure, short-chain fatty acid (SCFA) detection to assess metabolic function, and endotoxin assays to monitor inflammatory potential. This framework, born from community feedback and refined by industrial expertise, was designed to provide a holistic view of our project’s ecological safety.

See our Safety journey

Accomplishment: Co-developing Safety Standards

We believe that pivotal safety insights should be shared and codified. The presentation from iZJU-China at our exchange meeting was a key turning point. Their elegant use of DNA origami was more than just a clever technique; it was a tangible example of the proactive “Safety by Design” philosophy that had resonated so strongly with us.

This specific example crystallized the day’s discussions into a powerful realization: these advanced safety concepts were too valuable to remain as isolated ideas within a single meeting. This became the direct catalyst for our proposal to iZJU-China: to collaborate and transform these innovative principles into a lasting, practical resource for the entire community. Our two teams joined forces to co-draft a set of Safety Standards for Live Biotherapeutics. The workload was shared: our Peking team drafted the core standards and consulted with enterprises for revisions, while iZJU-China enriched the document with relevant iGEM project examples and handled the graphic design. This collaborative process transformed the reflections from a single meeting into a practical guide, ensuring our safety journey culminated not just in a safer project, but in a valuable contribution to the collective wisdom of iGEM.

Figure 16-18: The iGEM Safety Standard for Engineered Live Biotherapeutic Products, co-authored by our team and iZJU-China, transforming our collective safety insights into a practical resource for future teams.

See our Safety journey

Part 4 - Public Communication Strategy: From Dialogue to Trust

During the initial stages of our project, an interview with a professor from our university’s School of Environmental Sciences left a profound impact on us. He expressed a clear and strong opposition to gene editing and synthetic biology. While we understood that public attitudes vary, this direct encounter with academic skepticism was sobering. It made us realize that we could not remain passive. To prevent misconceptions and reduce unnecessary panic, we understood that a rational and empathetic public communication strategy was not just an option, but an essential responsibility.

Foundational Education

Our first step was to proactively address misinformation. On our official WeChat account, we launched a series of popular science articles to build a foundational understanding. These posts systematically introduced the core concepts of synthetic biology, clarified common public misconceptions, and detailed the rigorous risk control strategies that govern the field. This foundational work led to more targeted efforts, such as our collaboration with the CJUH-JLU-China team on their popular science booklet, “Debunking Myths in Synthetic Biology.” Our chapter focused specifically on debunking the myth that “engineered probiotics are ‘unnatural’ and dangerous to ingest,” aiming to enhance public scientific literacy.

Figure 19: Our contribution to the "Crushing the Myths of Synthetic Biology" popular science booklet, a collaborative effort with team CJUH-JLU-China. This chapter directly addresses public misconceptions by explaining the safety of our engineered probiotic chassis.

Strategic Refinement

To further refine our approach, we sought advice from our corporate partners. Junchangyi taught us to ground our communication in a deep understanding of patient pain points and to strategically “create acceptance” through endorsements like iGEM awards and expert collaborations. Similarly, Xbiome advised us to frame our narrative around the benefits—a gentler, more efficient treatment—rather than the intimidating details of “genetic engineering.” We immediately put this into practice. In our subsequent educational courses for students, we consciously avoided complex explanations of gene circuits. Instead, we used vivid, relatable metaphors, describing our engineered probiotics as “probiotic special forces” on a mission to “attack” harmful bacteria, making the science accessible and positive.

Part 5 - Entrepreneurship & Future Vision: Translating Science into Societal Impact

We believe that a promising research project must ultimately answer the question of “how to move from the lab to the real world.” This conviction was reinforced early in our project during our consultation with M.D. Zhanlong Shen, who emphasized that a truly impactful therapeutic must consider the entire lifecycle, including production processes, quality control, regulatory requirements, and public communication. This advice became the guiding principle for our industrial outreach. To explore the future industrialization path of our project, we stepped out of the academic ivory tower to learn from pioneers in the field, seeking to understand the full picture of bringing a scientific vision to reality.

Figure 20: Our entrepreneurial roadmap, illustrating how interactions with competitions and industry leaders guided our project's development from an initial idea to a strategic plan.

BioHackathon: Defining Our Social Value

Participating in the iGEM BioHackathon during our early brainstorming phase was a critical turning point. Our initial idea of using aptamers to detect harmful environmental small molecules was questioned by judge Mr. Florian Kroh regarding its timing and theoretical nature. This crucial feedback forced us to recognize that a successful iGEM project must be anchored to a clear and genuine societal need. Consequently, we revisited our ideas and ultimately chose to focus on treating Helicobacter pylori, a direction with a defined clinical need and higher social value. This experience taught us to frame our project from a “problem-solving” perspective, a mindset that proved essential for our subsequent industrial explorations.

Figure 21-22: Our participation in the iGEM BioHackathon, where critical feedback from judges helped us pivot to a project with clear clinical and social value.

Bluepha: Defining a Practical Path

With our problem defined, our next challenge was to shape a solution that was not only scientifically sound but also practical and impactful. To gain an early industrial perspective, we consulted with Dr. Haoqian Zhang, a Peking University alumnus and the founder and CEO of the biotechnology company BluePHA. Dr. Zhang emphasized that a well-executed synthetic biology project should be either “complex and elegantly engineered” or “simple and highly practical.” This principle became a core tenet of our design philosophy. His advice to analyze existing commercial solutions, such as the probiotic therapy Pylopass™, was invaluable, prompting us to research the competitive landscape and refine our project’s unique value proposition. This dialogue provided us with a high-level strategic framework and reinforced the importance of grounding our technical design in real-world viability, setting the stage for more detailed industrial investigations.

Figure 23: Core design philosophy from Mr. Haoqian Zhang of BluePHA, which guided us to build a practical and impactful solution.

Junchangyi: Entrepreneurship with a Human Touch

Dr. Zhang’s strategic advice gave us a foundational industry perspective. To delve into the specific operational details of industrialization—from large-scale production to regulatory pathways—we initiated a series of targeted visits to leading companies in the synthetic biology field. Our journey into this industrial landscape began at Junchangyi, a pioneering company specializing in Fecal Microbiota Transplantation (FMT) and the industrialization of living biotherapeutics.

Figure 24-26: Our visit to Junchangyi, where we learned about the industrialization path for living biotherapeutics and the importance of human-centered design.

Our discussion with their general manager, Mr. Zhenyu Wang, gave us a holistic view of the entrepreneurial landscape. We were deeply impressed by their “practice first, do first” entrepreneurial methodology and their outline of the complete path from an idea to a final product. A key takeaway was the importance of “creating acceptance” for new technologies by establishing authority through publishing papers and applying for patents. This concept directly inspired our subsequent collaboration with iZJU to jointly develop safety standards for live biotherapeutics—our own effort to “create acceptance” for the entire field.

See our Safety journey

Furthermore, their “people-oriented” innovation of changing a product from a saline dilution administered via cannula to a simple oral capsule made us realize that excellent engineering design must incorporate humanistic care for the user.

BGI: Insights on Scale-up and Compliance

That same day, our exchange at BGI, a global life sciences leader with unparalleled expertise in genomics, large-scale production, and regulatory affairs, allowed us to focus on the most critical backend issues of industrialization. Experts at BGI confirmed the wisdom of choosing a chassis like Saccharomyces boulardii, whose mature history of industrial application helps circumvent scale-up and process amplification problems. The key challenge, they noted, becomes verifying that our genetic modifications have not altered its original production characteristics. They also illuminated the stark regulatory differences between “drugs” and “functional foods,” which directly informed our product positioning.

Figure 27-30: Exchanging with experts at BGI, which provided critical insights on production scale-up, regulatory compliance, and quality control.

Most importantly, their advice on using high-throughput sequencing to monitor genetic stability was formative. We immediately integrated this critical insight into the Quality Control (QC) section of the Safety Standards for Live Biotherapeutics that we were co-developing with iZJU-China, transforming an industrial best practice into a community-wide guideline.

Xbiome: AI-Driven Strategy and Positioning

Our industrial exploration culminated in a visit to Xbiome, a cutting-edge AI-driven drug discovery company focused on the gut microbiome. Their work revealed the power of technology in modern R&D. We learned that AI-powered high-efficiency screening can dramatically shorten the traditional R&D process from years to months, a crucial insight for making our project more cost-effective.

Critically, our discussion with Xbiome clarified the strict regulatory distinction between genetically engineered microbes as “drugs” versus “health supplements.” They pointed out that engineered organisms cannot be sold as supplements interiorly. This feedback was pivotal, causing us to abandon our initial idea of mixing our engineered yeast powder into biscuits and instead adopt a more medically appropriate capsule-based delivery system. These invaluable, real-world lessons from our enterprise visits provided us with a clear and pragmatic understanding of our project’s future path to applicatio.

Figure 31-34: Our consultation at Xbiome, which provided pivotal regulatory advice that finalized our product's positioning and delivery strategy.

SWOT Analysis: Charting Our Path Forward

To synthesize the invaluable insights from our industrial outreach and formulate a clear, forward-looking strategy, we conducted a comprehensive SWOT analysis. This framework integrates the high-level strategic advice from Bluepha, the practical entrepreneurial wisdom from Junchangyi, the scale-up and regulatory knowledge from BGI, and the cutting-edge R&D perspective from Xbiome.

Our analysis confirms the project’s core Strengths, including its response to a clear market need for new H. pylori treatments, the use of the industrially proven S. boulardii chassis, and our innovative, multi-system therapeutic design. We also honestly assessed our Weaknesses, primarily the early, lab-phase nature of our technology and the manufacturing complexities associated with a genetically modified organism and a novel delivery system.

Crucially, this analysis illuminated significant Opportunities. There is a distinct market gap for effective non-antibiotic treatments, and our project can be positioned as a cutting-edge “live biotherapeutic.” We also see a clear opportunity to leverage AI to accelerate R&D and to take a leadership role in co-developing safety standards for the entire field. Finally, we identified key Threats, including the stringent regulatory pathway for a GMO drug, the challenge of gaining public acceptance, the need to secure strong intellectual property, and the presence of intense market competition. This strategic framework provides us with a realistic and actionable roadmap for navigating the complex journey from laboratory research to real-world clinical application.

Figure 35: A comprehensive SWOT analysis for the Industrialization of Our Live Biotherapeutic, synthesizing our industry learnings to evaluate our project's commercial potential.

Part 6 - Scientific Community Outreach: Weaving a Web of Collective Wisdom

We hold a core belief that science, at its best, is not a monologue delivered from an ivory tower, but a vibrant, living conversation. No project is an island, entire of itself; its true potential is only unlocked through the dynamic interplay of communication, intellectual collision, and generous mutual assistance with peers. Driven by this philosophy, we consciously chose to step out of our lab and immerse ourselves in the broader scientific community. We were not just presenters of our work; we were active listeners, eager students, and passionate collaborators, seeking to share our vision for HpBuster and, in turn, have it sharpened and enriched by the collective wisdom of others. We knew that by joining hands with like-minded pioneers, we could transcend the boundaries of our individual projects and contribute to the grand, collaborative tapestry of synthetic biology.

Live Biotherapeutics Exchange Meeting

Recognizing a shared struggle among iGEM teams venturing into the complex world of live biotherapeutics, we took the initiative to host a dedicated symposium. The gathering blossomed into a vibrant congregation of 28 teams from 24 universities. We shattered the initial formality with a “lightning introduction” ice-breaker, creating a whirlwind of creativity that immediately bonded the room.

Figure 36: 28 iGEM teams from 24 universities gather at the Live Biotherapeutics Exchange Meeting to discuss the frontiers of synthetic biology.

The intellectual tone was set by our honored guest, Director Liu Chenli from the Shenzhen Institute of Advanced Technology (SIAT). His opening words resonated deeply, framing “safety” and “controllability” not as mere technical checkboxes, but as the very lifelines upon which the future of our field depends. This powerful message became the guiding principle for the day’s discussions.

Figure 37: Director Liu Chenli of SIAT delivers the opening address, emphasizing "safety" and "controllability" as the lifelines for the future of live biotherapeutics.

Inspired by this charge, the symposium unfolded around three critical pillars. Teams took the stage to share their work, first wrestling with The Navigator’s Dilemma of Targeted Delivery and Sensing. Then, we delved into The Architect’s Blueprint for Designing Therapeutic Logic, exploring the sophisticated genetic circuits that transform microbes into smart therapeutics. The final and most critical session confronted The Guardian’s Oath of Safety and Controllability. Each presentation was more than a showcase; it was a catalyst for collaborative problem-solving, sparking deep dialogues on engineering trade-offs, the philosophy of genetic design, and our shared ethical duties.

Figure 38: A Peking team member presents our project design during the "Targeted Delivery and Sensing" session, contributing our solution to one of the field's key challenges.

Figure 39: From engaging questions from fellow iGEMers (left) to insightful feedback from experts like Dr. Bing Zhai (right), deep interaction was the key to collaborative problem-solving.

Yet, the most poignant moments of connection occurred in the spaces in between. The animated chatter during the poster session, the informal debates over coffee, and the powerful symbolism of the “Problem Wall”—a board where anonymous research hurdles were met with a flurry of helpful suggestions—all spoke to a community built on trust and mutual support.

Figure 40: Animated discussions during the poster session fostered intellectual exchange among teams and built a community founded on mutual trust and support.

Figure 41: The "Problem Wall" embodied the event's collaborative spirit, allowing participants to anonymously post research hurdles and crowdsource solutions from the community.

The day concluded with a heartfelt speech from Dr. Bing Zhai of SIAT. She spoke not as a distant authority, but as a compassionate mentor, sharing real-life clinical stories that reminded us to ground our ambitions in a profound reverence for life. Her words were a powerful charge to us all: as scientists holding “Pandora’s box,” we must wield our power with humility, humanistic care, and unwavering creativity.

Figure 42: In her closing speech, Dr. Bing Zhai of SIAT encouraged us to wield the power of synthetic biology with humility and creativity, rooted in humanistic care.

Synbio Challenges

The very next day, on August 6, 2025, we found ourselves in Shenzhen for the 4th Synthetic Biology Innovation Competition, a premier academic event guided by the Chinese Society of Biotechnology. Competing in the Red Track (Medical, Health) , our project was put to the ultimate test, and we were thrilled when our “Construction of Engineered Saccharomyces boulardii for the Treatment of Helicobacter pylori” was awarded the Gold Medal. The final presentation was a crucible; we not only had to present our innovative design with clarity and conviction but also address challenging questions announced just before the finals. Drawing on our experimental data and supporting literature, we fluently defended our project’s feasibility and scientific rigor under a barrage of sharp questions from the judges. It was a moment that solidified our confidence and validated our hard work.

Figure 43: Presenting our HpBuster project during the SynBio Challenges Finals.

Figure 44: Our project wins the Gold Medal at the 4th Synthetic Biology Innovation Competition, a significant validation of our hard work and therapeutic potential.

But the competition was more than just a contest; it was a festival of ideas. During the lively poster session, we shared our design concepts with students and faculty, and the feedback we received sparked crucial ideas for improvement. Listening to the candid stories of young entrepreneurs who had navigated the perilous journey from academia to industry gave us a sobering, yet inspiring, glimpse into our own potential futures. The “Carnival Night” was another highlight, where activities from a playful “Plasmid Kill” game to a thought-provoking “Synthetic Gene Debate” allowed us to connect with other teams, share our understanding of synthetic biology, and build valuable friendships. Through these interactions, we came to a deeper realization that the responsible development and regulation of this emerging technology is the shared duty of all life scientists.

Figure 45-46: Engaging in deep scientific discussions during the poster session (left) and sharing our project's vision in an interview (right).

Figure 47: Our team members connect with other participants during "Carnival Night," building friendships and a shared vision in a relaxed, interactive setting.

the 12th Conference of China iGEMer Community (CCiC)

Our journey culminated at the 12th Conference of China iGEMer Community (CCiC) and the 2nd Global Bio-developer Conference, held from August 6-8 at the Beijing Zhongguancun Exhibition Center. This was the grand symphony. Through our PPT roadshow and detailed poster, our project became a nexus for conversation, drawing in seasoned researchers, industry veterans, and fellow iGEMers. It was here that a challenging question about the long-term ecological safety of our engineered yeast, posed by a senior professor, forced us into a deep and necessary re-evaluation of our project’s containment strategy. The collaborative spirit was palpable; a serendipitous and lengthy discussion with the Fudan team, who were also navigating the labyrinth of GPCR modification, yielded a breakthrough perspective that untangled a knot in our own design. We also had friendly exchanges with other teams, such as Nanjing Agricultural University (NAU), further strengthening our community bonds.

Figure 48-51: Immersion in the CCiC Community. Clockwise from top left: Our team proudly representing Peking iGEM; presenting our work during the roadshow; the vibrant atmosphere of the conference; and engaging peers during the poster session.

Beyond our project, we aimed to contribute to the broader dialogue. Our dry lab captain initiated and organized a Syncamp (self-organized meeting) session on AI Virtual Cells (AIVC). The topic captured a forward-looking trend, sparking intense interest and a highly engaging discussion among attendees about the future of integrating AI with synthetic biology. The crowning moment was when our poster was named a Top 10 project (4th place) in the synbiopunk-challenge. This recognition was not just an award; it was a powerful affirmation from the community we so deeply respected, a sign that our voice was heard and our contribution valued.

Figure 52-54: A Crowning Moment at CCiC. The certificate (right) and the award ceremony (top left) mark a key achievement in our iGEM journey, and our dry lab lead on the self-organized meeting on AIVC (bottom left).

Through this rich tapestry of interactions, our project was transformed. It evolved from a concept born in our lab into a robust, well-vetted, and community-enriched endeavor. We returned not just with data and feedback, but with a renewed sense of purpose and a profound appreciation for the collaborative spirit that is the true heartbeat of scientific progress.