Description

Introduction

In today’s highly competitive and challenging society, the successful advancement of any project relies on scientific planning, effective execution, and continuous optimization. Throughout the development of our project, our team has consistently upheld a rigorous, responsible, and innovative attitude. We have systematically integrated project milestones and stage achievements, deeply articulated the core significance of the project’s inception, and successfully realized a hybrid practice model that combines both online and offline approaches. By doing so, we established a closed-loop mechanism of “Practice – Review – Optimization – Implementation,” laying a solid foundation for the long-term development of the project.

Figure 1: Home Wiki

At the outset, our team carried out a comprehensive and meticulous integration of project schedules and stage outcomes. A detailed project timeline was established, dividing the overall work into clearly defined phases, each with specific milestones and task objectives. Regular project progress meetings and a real-time reporting mechanism allowed us to closely monitor the advancement of each stage and promptly address any deviations through timely adjustments.

Project Establishment Stage

Before finalizing the project topic, our team conducted extensive information collection through multiple channels: literature review, questionnaire surveys, expert consultations, and repeated brainstorming sessions among team members. Based on this multidimensional and multilayered research, we ultimately identified lactic acid chemotaxis engineered Escherichia coli for the de novo biosynthesis of all-trans retinoic acid (ATRA) in the treatment of liver cancer as our iGEM 2025 project.

Prior to officially confirming the project, the team spent nearly a month conducting a systematic, multidimensional, and interdisciplinary “pre-research” phase:

• Literature research: Using Web of Science, PubMed, and CNKI as the core databases, and extending to patent libraries, arXiv, and past iGEM track reports, we conducted over 120 keyword searches, carefully reviewed 186 high-level papers, summarized 87 potentially reusable BioBricks, and compiled a “Research Gap and Opportunity Map.”
• Interviews: We conducted in-depth semi-structured interviews with several top-tier hospitals (average duration: 52 minutes), obtaining 7 sets of unpublished frontline data and identifying 9 implicit regulatory “thresholds.”


Figure 2: Interviews

• Brainstorming: The team adopted a “dual-cycle” creativity mechanism:
  • Monday Free Divergence Cycle: Encouraging bold hypotheses, generating 137 initial ideas.
  • Thursday Convergent Evaluation Cycle: Assessing ideas with a four-dimensional scoring matrix (technical feasibility, commercial potential, ethical compliance, and iGEM judging preferences). After 5 rounds of screening and 2 rounds of SWOT-AHP quantitative analysis, the pool was narrowed to 3 candidate topics.


Figure 3: Brainstorming

• Cross-validation: We matched literature hotspots, interview insights, and top-ranked brainstorming ideas, applying a 0–1 integer programming model to calculate a “fitness index.” The ATRA liver cancer treatment project scored 0.92, far ahead of other candidates, and was unanimously established as the team’s research focus.

Thus, we did not merely “choose” a project, but rather anchored it within a robust and sustainable framework spanning data, societal needs, technology, and ethical considerations.

Project Initiation Phase

At the germination stage of our project, we carried out a systematic integration of knowledge and innovative transformation across disciplines, regions, and languages. Starting from authoritative global data sources such as The Lancet, WHO, FDA, the National Cancer Center of China, Zhongshan Hospital affiliated with Fudan University, and the Third Affiliated Hospital of the Naval Medical University, we searched, screened, compared, and translated hundreds of papers published within the past five years in top journals including Signal Transduction and Targeted Therapy, Science Immunology, and Nature Nanotechnology. From these, we extracted the latest evidence on the epidemiology, risk factors, treatment modalities of liver cancer, and the multi-cancer applications of ATRA.

Subsequently, we conducted cross-validation and trend projection of key indicators—incidence, mortality, etiology, high-risk population profiles, and survival rates of surgery/targeted/immunotherapy/cell therapy—at four levels of granularity (global → China → regional → hospital). This yielded a comprehensive map of the current status of liver cancer that combines an international perspective with local depth.

On this basis, focusing on the original drug all-trans retinoic acid (ATRA) developed by Chinese scientists, we provided a full-chain interpretation covering:

• Mechanistic level: induction of differentiation, immune microenvironment reprogramming, AKT inhibition, and loss of stemness in tumor-initiating cells;
• Clinical evidence: Phase III RCT showing OS 16.2 months and ORR 24.5%;
• Health economics: cost per treatment cycle of RMB 329 (≈1/30 of typical IO combinations);
• Real-world accessibility: coverage in primary hospitals increased from 35% to 60%.

Furthermore, we incorporated into the analysis:

• 60% cost reduction achieved by cell-engineered yeast biosynthesis of ATRA;
• Expansion across multiple indications (APL, MDS, breast cancer, psoriasis, diabetic nephropathy);
• Novel delivery systems (liposomal ATRA, PLGA microspheres);
• Socioeconomic impacts of insurance reimbursement, DRG/DIP payment reforms, and regional market balance.

Ultimately, through a unified academic language, hierarchical headings, a progressive five-part structure, and more than ten high-resolution figures, we transformed fragmented information spanning basic research, clinical practice, industry, and policy into a comprehensive background document. The output is logically coherent, data-traceable, guideline-informative, and industry-applicable—providing a “one-click reference” knowledge base to support subsequent project progress, experimental design, human practices, and outreach.

Project Implementation Phase

1. Expert Interviews

To better understand current treatments for liver cancer, we interviewed two surgeons: Dr. Qin from Shengjing Hospital and Dr. Li from the First Affiliated Hospital of China Medical University. Their clinical experiences were complementary. Dr. Qin noted that patients were usually aged 40–60, with a male-to-female ratio of ~3:1, while Dr. Li emphasized both physical and psychological suffering. Both observed that many patients only sought medical attention when severely ill.

Figure 7: Doctor Li

On treatment, both mentioned morphine analgesia, drainage for ascites, and partial hepatectomy in severe cases, but noted the high recurrence rate. They stressed lifestyle adjustments including diet, exercise, and sleep. Dr. Li recommended research on drug-resistance and development of ADC therapies (e.g., HER3-ADC), while Dr. Qin highlighted the cost factor. They acknowledged that no ATRA-based liver-cancer therapy currently exists, confirming the novelty of our approach.

2. Patient Surveys

To further capture patient perspectives, we distributed 319 questionnaires across four medical centers, recovering 311 valid responses (96.3%). Results showed that 78% of late-stage patients were willing to join ATRA+chemotherapy trials, with only 17% expressing concerns about transport or side effects. Economic data revealed a monthly out-of-pocket average of 8,700 RMB, with 48% of families earning under 30,000 RMB annually.

These findings directly supported travel-subsidy policies and insurance negotiations for low-cost therapies, while enabling more inclusive clinical-trial recruitment.

Figure 8: Patient Survey

The database built—linking “patients–needs–economy”—became a cornerstone for health-economic modeling and real-world evidence.

3. Patient Information Collection

Our survey and interviews enabled systematic collection of patient information:

• Symptoms: Right upper abdominal pain, weight loss, fatigue, jaundice, palpable masses, and complications triggered by treatment operations.
• Triggers: HBV infection, metabolic fatty liver, alcohol and tobacco use, aflatoxin exposure, chronic liver diseases, metabolic disorders, and hereditary factors.
• Treatment options: Ranging from surgery, ablation, transplantation, and systemic therapy (targeted/immunotherapy, TACE, HAIC) to drugs such as lenvatinib and tislelizumab. Lifestyle interventions were also emphasized.
• Impact on life: Physical suffering, appearance changes, psychological burden, high treatment costs, social stigma, and distrust toward conventional medicine.

Figure 9: Wechat Group(a)

Figure 10: Wechat Group(b)

Many patients expressed skepticism toward existing drugs yet showed strong curiosity and hope for innovative therapies, highlighting the necessity for safe, effective, and affordable new treatments like our engineered ATRA approach.

3.1 Analysis of 3D Tumor Geometry for BCLC Stage Characterization

Summary. To quantitatively link tumor morphology to clinical staging, we processed 3D models of hepatocellular carcinoma (HCC) tumors, extracted comprehensive geometric features, and performed statistical & visual analyses. These descriptors show strong correlations with the Barcelona Clinic Liver Cancer (BCLC) staging system, providing a data-driven foundation for our diagnostic tool.

1) Data Overview and Sample Distribution

We first examined the sample distribution across BCLC stages (A, B, C, D). The dataset is imbalanced in a way that reflects real-world prevalence—an important consideration for downstream modeling and evaluation.

2) Geometric Feature Extraction

From each 3D tumor mesh, we computed a wide range of descriptors:
Size: Volume, SurfaceArea, BBox_X/Y/Z_dim, BBox_Volume.
Shape complexity: Sphericity, Compactness, Convexity, Solidity.
Structural distribution: Anisotropy, AspectRatio_MaxMin/MaxMed/MedMin, Extent.
Statistical distances: Mean/Std/Skew/Kurtosis of vertex distances to the centroid.

3) Descriptive Analysis and Staging Trends

Descriptive statistics across stages reveal clinically meaningful trends: Volume/SurfaceArea increase from A→D, while Sphericity/Compactness tend to be higher in early stages. Advanced tumors show elongated and irregular shapes, consistent with lower Sphericity and higher Anisotropy.

4) Feature Correlation and Redundancy Check

Correlation analysis reveals expected relationships (e.g., Volume ↔ SurfaceArea/BBox_Volume). Sphericity positively correlates with Compactness and negatively with Anisotropy, indicating complementary shape descriptors. Mesh complexity metrics (NumVertices/NumFaces) show relatively low correlation with shape features, adding orthogonal information.

5) Multivariate Relationships and Dimensionality Reduction

Pairwise analyses (e.g., Volume vs. Sphericity) show separability between stages when combining features. Principal Component Analysis (PCA) further condenses these descriptors: PC1 and PC2 explain 54.3% of total variance (PC1: 34.3%, PC2: 20.0%), with visible clustering of BCLC stages in 2D space.

6) Stage-Specific Geometric Profiles

Radar charts summarize normalized geometric signatures for each stage: Stage A—high Sphericity & Compactness, low Volume; Stage B/C—intermediate/transitional patterns; Stage D—very high Volume & Extent, low Sphericity.

Conclusion. Computational morphology (size, shape complexity, structural distribution, and vertex-distance statistics) aligns strongly with BCLC staging. These findings underpin our subsequent machine-learning classifier, moving toward a reliable computational aid for liver cancer staging.

4. Drug and Therapy Outlook

Despite mistrust in current therapies, patients often responded positively when introduced to new drugs with innovative mechanisms, such as FDA-approved dual immunotherapy agents. This demonstrates a strong unmet demand for novel therapies. Our solution, employing ATRA-producing E. coli Nissle 1917 with lactate chemotaxis, directly addresses concerns of efficacy, safety, and sustainability.

By emphasizing environmentally friendly, probiotic-based delivery systems, we designed a therapeutic approach that aligns with patient expectations and regulatory trends, while alleviating misconceptions about liver cancer and its treatment.

During the implementation phase, we observed that patients often lacked basic knowledge about liver cancer and its treatments. Many held misconceptions such as believing that only long-term alcohol abusers would develop liver cancer, that the disease is strictly hereditary, or that health supplements could prevent or cure liver cancer. Such misunderstandings sometimes led patients to misuse supplements as medicine, causing confusion about drugs, conditions, and healthcare professionals.

To address these issues, our Human Practices team collaborated with Jilin University to produce a popular science brochure on synthetic biology. This brochure aimed to clarify common misconceptions, provide accurate scientific information, and promote public understanding of both synthetic biology and innovative therapies. By simplifying complex concepts into accessible language and visuals, the brochure helped patients, families, and the general public better appreciate the significance of our project and the potential of ATRA-based treatment for liver cancer.

Figure 11: Popular Science Brochure

5. Visual Documentation

During this phase, we systematically implemented a “visual evidence chain.” At the video level, we recorded experiments in 4K with dual cameras, capturing aseptic operations, inoculations, and drug-sensitivity dilutions, with timestamps and voiceover to ensure reproducibility. At the image and text level, high-frame photos and lab notes documented our team’s rigorous attitude.

We also iterated process flowcharts, quality-control tables, and risk-assessment matrices. Together, this built a traceable system integrating video, imagery, and text, providing strong visual support for later scale-up.

Figure 12: Drug and Therapy Outlook

6. Collaborations and Conferences

Throughout the project, we actively engaged in collaborations and conferences to broaden our perspectives and strengthen our project. Highlights include our plasmid exchange with OUC-Haide, participation in the Northeast iGEM Regional Exchange (Xinmin), and presenting at the 12th CCiC Conference in Beijing. These activities not only enabled knowledge sharing but also provided valuable feedback, inspiring improvements in our project design. For detailed records of interviews, exchanges, and outcomes, please visit our Communication page.

7. Promotion and Branding

7.1 Dual-Track Outreach: "One Article, Multiple Platforms; One Screen, Multiple Views"

In the promotion stage, our strategy followed the dual-track approach of "one article, multiple platforms; one screen, multiple views". On the article side, we focused on WeChat, publishing multiple in-depth posts centered on ATRA and liver cancer, while simultaneously showcasing our team spirit. On the video side, we regularly updated science popularization videos on Bilibili, which gained significant viewership. This strategy successfully achieved cross-platform resonance through “WeChat in-depth engagement + Bilibili viral diffusion.”

Figure 17: Dual-Track Outreach(a)

Figure 18: Dual-Track Outreach(b)

7.2 Cultural and Creative Products

We designed cultural and creative products integrating our team identity. The design incorporated the acronym “syphu” (Shenyang Pharmaceutical University), combined with gear elements inspired both by engineering concepts in synthetic biology and by the gear motif in the iGEM logo. The colorful design of the five letters represented our perseverance during the competition and our contributions to society. Transparent shells symbolized our team’s sincerity toward knowledge and commitment to the iGEM spirit, while the gears reflected our dedication to exploration and innovation throughout the experimental process.

Figure 19: Cultural and Creative Products

7.3 Logo

The project logo plays a crucial role in any project, prompting us to reevaluate our aesthetics. Its significance goes beyond visual appeal; it is a visual representation of the project’s identity, values, and goals. Moreover, a well-designed logo can effectively convey the mission and vision of the project, ensuring clear and memorable communication across various platforms. Therefore, the project logo is essential for effective communication within the team.

Figure 20: Logo Design

During our team-building process, the logo underwent several design iterations, and we also endowed it with unique meaning. 2025 signifies that it was designed for the 2025 iGEM competition, representing the year of participation. The gear-inspired technological elements symbolize the engineering applications of various biological components, reflecting the characteristics of Shenyang Pharmaceutical University and our research field. The combination of gears and letters embodies the principles of engineering applied to biological systems in synthetic biology. The vibrant and dynamic colors further highlight the inherent diversity and creativity of synthetic biology.

Project Integration Phase

Entering the project integration phase, we transformed the previously scattered massive searches, multiple expert interviews, data cleaning, and visualization drafts into a coherent and consolidated framework. All the fragmented information once stored across five different folders—epidemiology, mechanistic studies, clinical trials, cost estimation, and policy scenarios—was reorganized under a progressive logic: Problem Pain Points → Solutions → Differentiated Advantages → Commercialization Pathway → Social Value.

This process culminated in the creation of a condensed English PowerPoint presentation that clearly communicated the essence of our project. Within the same week, we also deconstructed the assumptions, data sources, competitive landscape, risk matrices, financial models, and funding rhythms underlying the presentation into a well-structured business plan. The document was written with clarity and logical rigor, ensuring that future project stages could quickly reference critical parameters without ambiguity.

By adopting this dual-output approach—“PPT for presentation” + “Business Plan for execution”—we effectively compressed our early scattered efforts into a roadshow-ready, proposal-ready, and implementation-ready integrated package. This provided a one-stop set of materials to support subsequent project progress, experimental design, external communication, and stakeholder engagement.

Figure 20: Integration