Our team, XJTLU-Science-China, has reached out to 32 experts from various fields, 4 schools, 2 research institutions, 4 hospitals, 8 iGEM teams, and 1 community.
Social Need and Project Origin
Triple-Negative Breast Cancer (TNBC) is one of the most aggressive subtypes of breast cancer, accounting for approximately 10-15% of all breast cancer cases. Unlike other subtypes of breast cancer, TNBC lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2, which means it cannot benefit from endocrine therapy or HER2-targeted therapy, making treatment options extremely limited. Currently, chemotherapy is the primary method for treating TNBC. However, existing treatment methods face significant limitations, particularly in terms of efficacy, treatment duration, and managing side effects.
Real-Life Challenges and Urgent Needs
Through interviews with patients and doctors, we deeply felt the severe impact of current treatment regimens on the quality of life of patients. Patients commonly reported that while chemotherapy could control the tumor in the short term, the side effects were severe and the treatment effect lasted only a limited time. Low long-term survival rates, along with high rates of recurrence and metastasis, are major challenges for TNBC patients. At the same time, many doctors also mentioned that the lack of effective targeted therapies makes current treatments too singular, and there is an urgent need for a new, more precise treatment regimen that can effectively improve the quality of life and long-term efficacy for patients.
We interviewed a 45-year-old TNBC patient, whose experience revealed the shortcomings of existing treatment methods. Sun cuiyun’s story began with a routine physical exam, where a doctor discovered a lump in her right breast that was less than 2 cm in diameter. At that time, there were no obvious signs of pain or skin changes, and she was busy with work, so she did not pay much attention. However, three months later, the lump gradually grew and became tender, prompting her to visit the hospital. After imaging tests (including breast ultrasound and mammography), the doctor suspected the lump might be malignant. A biopsy and immunohistochemical tests eventually confirmed her diagnosis: TNBC. For Sun, this diagnosis was undoubtedly a heavy blow, especially when she learned that TNBC lacks effective targeted therapies, and current treatments rely solely on chemotherapy.
“The doctor told me that chemotherapy is the only option right now, but the side effects are huge.”
— Sun cuiyun
She mentioned that chemotherapy not only caused severe physical discomfort, such as full-body swelling and severe hair loss, but also significantly reduced her quality of life. She expressed strong dissatisfaction with the existing treatment methods, stating that this treatment was “like killing one thousand enemies, but injuring oneself eight hundred.” While the side effects could temporarily control tumor growth, they severely damaged her health and quality of life. Nonetheless, she also expressed that if she could endure the first five years, the recurrence and metastasis rate would significantly decrease, so she remained optimistic and faced the treatment with hope for the future.
Challenges and Needs from Clinical Doctors
In an interview with Professor Min Tao, Head of the Oncology Department at the First Affiliated Hospital of Soochow University, we gained a clearer understanding of the practical challenges in treating TNBC. Professor Tao pointed out that the treatment of TNBC has always been a significant challenge in oncology. Although chemotherapy can delay disease progression to some extent, due to the lack of specific targets, the effects usually last for a short period, and the risk of recurrence and metastasis always exists. He mentioned that patients often suffer from both physical and psychological burdens, and as doctors, they feel helpless with such limited treatment options.
“Triple-negative breast cancer lacks effective targeted treatments. While chemotherapy can temporarily control the tumor, the side effects are severe, and patients’ quality of life significantly decreases. We urgently need a more precise, gentle, and effective treatment approach.”
— Professor Min Tao
Professor Tao emphasized that with advancements in technology, emerging therapies such as immunotherapy, nanoparticle technology, and bacterial therapies have made some breakthroughs. However, these technologies are still in the preclinical or early stages and have not been widely applied. Therefore, exploring more precise drug delivery platforms is key to solving the treatment challenges of TNBC. Doctors urgently need a method to accurately target drug delivery within the tumor microenvironment to reduce damage to healthy tissues and improve treatment efficacy.
Project Inspiration and Technical Breakthroughs
In recent years, the scientific community has gradually realized that tumors are not composed solely of abnormally proliferating cells, but are instead complex ecosystems. Within this system, in addition to tumor cells and host immune cells, there exists a long-neglected “third resident” — intratumoral bacteria.
Studies have shown that bacteria can be detected in many solid tumors (including breast cancer, pancreatic cancer, and lung cancer). These bacteria are not “accidental invaders,” but are able to survive long-term within the tumor microenvironment. By regulating immune responses, participating in metabolic pathways, and even influencing drug efficacy, they play a profound role in tumor occurrence and development. In particular, in Triple-Negative Breast Cancer (TNBC), the enrichment of intratumoral bacteria is significantly higher than in normal tissues, suggesting a close relationship with the tumor’s unique pathological environment.
Inspiration from Dr. Cai Shang
In this field, the research of Dr. Cai Shang’s team at Westlake University provided us with direct inspiration. Through metagenomic sequencing, in situ hybridization, and single-cell level analysis, they revealed the presence of specific bacterial communities within TNBC tissues. These bacteria are not only capable of surviving inside tumor cells but may also play a key role in tumor progression.
Our Technical Path
Driven by these scientific advances and urgent societal needs, we proposed the idea of using engineered bacteria to construct a drug delivery platform. We chose Staphylococcus epidermidis and Staphylococcus xylosus, which have stronger colonization abilities inside TNBC cells, and expressed the fnbA gene from Staphylococcus aureus within them to enhance adhesion specificity to cancer cells. At the same time, we placed drug expression downstream of the hypoxia-inducible promoter P_narT, ensuring that the drug is released only in the hypoxic tumor environment, thereby achieving precise, gentle, and controllable therapy.
This inspiration did not arise out of thin air but was formed by combining the accumulated results of intratumoral bacteria research with the urgent needs of clinicians and patients. We believe that this platform not only offers a new therapeutic approach for TNBC but also opens a new direction for future cancer treatment.
Stakeholder
During the course of the project, we referred to the IHP Handbook compiled by Stanford University, based on this, decided to proactively seek feedback from stakeholders related to our project. This decision was not coincidental but based on our deep understanding of the need to closely align our project with societal demands. We wanted to ensure that our research always remained in line with societal needs, avoiding disconnection from reality, and ensuring the project could bring tangible societal benefits.
Our Stakeholders
Our stakeholders primarily include the next generation, patients, potential patients, researchers, doctors, and pharmaceutical companies. Their feedback has provided us with the drive to improve our project and has helped us ensure that the project direction remains aligned with societal needs and has practical application feasibility.
How We Adjusted the Project Based on Feedback
Through in-depth communication with stakeholders, we continuously adjusted and optimized our research plan. After receiving feedback, we found that the current treatment options not only lacked precision but also had short-lived effects, significant side effects, and severely reduced the quality of life for patients. Therefore, we decided to further develop and improve our drug delivery platform, ensuring that it could meet patients’ actual needs in terms of precision, gentleness, and efficacy.
Wet Lab
During the experimental process, we received valuable help and guidance from field experts. Each expert’s advice helped us overcome difficulties in our experiments, ensuring the smooth progress of the project. Below are the specific feedback and improvements made:
Dr. Yongtao Zhu (2024/12-2025/03)
- Expert Contribution:
In the early stages of the team’s establishment, Dr. Yongtao Zhu actively communicated with the school, assisting in team building, and worked with Dr. Chun Chen to make an outstanding contribution to team member selection. As our main PI, Dr. Zhu provided us with many experimental reagents, antibiotics, and bacterial strains, which greatly advanced the progress of the project. His lab technician, Ge, also taught us some experimental techniques, helping us quickly get started. - How We Improved:
Dr. Zhu’s support allowed us to smoothly conduct experiments in the early stages, especially in preparing experimental materials and providing technical guidance, ensuring our research could start smoothly.
Dr. Lijuan Liu (2025/07)
- Issue We Found:
When our team started constructing fluorescent protein plasmids and the GFP-Fnbp plasmid, we initially planned to use the overlap PCR method. However, this method had several issues, such as being time-consuming, having a low success rate, and being difficult to operate, which slowed down our experimental progress and caused significant frustration. - Expert Advice:
To address this, we sought help from Dr. Lijuan Liu. After careful analysis, Dr. Liu’s team recommended using the One-step Cloning method for cyclization. This method was faster, simpler, and brought us great convenience. - How We Improved:
By adopting this method, we successfully locked the GFP-Fnbp construct into a circular form, solving the issues that had previously troubled us. The culture plates that had once frustrated us now quietly glowed under the UV transilluminator, and each green halo silently testified to the valuable lessons we had learned. With this improvement, our experimental efficiency significantly increased, and we successfully overcame the previous technical bottleneck.
Mr. Ziwen Xie (2025/03-2025/04)
- Issue We Found:
At the beginning of the project, we felt that our understanding of bacterial physiology was shallow, especially in designing the primitive modification system, which felt like an insurmountable barrier. - Expert Advice:
Mr. Ziwen Xie guided us to condense our iterative plan into simpler stages and remove redundant checkpoints. At the same time, he pointed out potential pitfalls we might encounter, such as subtle polymorphisms in restriction enzyme sites, unexpected metabolic burdens, and potential off-target recombination risks. Mr. Xie emphasized that ensuring each subsequent step was both feasible and rigorous was crucial. - How We Improved:
Based on Mr. Xie’s advice, we optimized the experimental design by breaking down complex processes into clearer and more simplified steps, avoiding unnecessary experimental steps. This not only made the experiment more feasible but also increased its accuracy. Mr. Xie also helped us guide the reagent procurement list, connected us with local biotechnology companies for sequencing and primer synthesis, and filled in gaps in our experimental experience.
Mr. Ziyang Lu (2025/06-2025/08)
- Issue We Found:
During a low point in the project, the shortage of experimental materials and the stagnation of progress caused significant pressure. - Expert Contribution:
Mr. Ziyang Lu generously provided a large number of antibiotics and experimental supplies, ensuring that our research could continue. He not only solved our shortage of experimental materials but also frequently visited the laboratory to provide us with moral support, helping us overcome technical difficulties. - How We Improved:
Mr. Lu’s help allowed us to maintain continuous motivation during the experiment. With his support, we not only obtained the necessary experimental materials but also became more familiar with the laboratory equipment and software under his guidance, enhancing our adaptability to the experimental environment and accelerating research progress.
Dry Lab
In the work of the modeling team, we also encountered some key technical issues, but through timely feedback and expert advice, we made the necessary adjustments to ensure the accuracy of the modeling process. Below are the specific issues, advice, and improvements for the modeling team:
Kevin (2025/06)
- Issue We Found:
During the early MD simulations, we were unable to generate RMSD images, which prevented the data from being effectively used for subsequent analysis. - Expert Advice:
Professor Kevin suggested we refer to the “trajectory PBC unwrap” section of the tutorial, especially regarding how to properly handle trajectory files. - How We Improved:
Following Professor Kevin’s suggestion, we added parameters such as -pbc nojump and -center -pbc mol -ur compact during the MD simulation process, successfully generating the RMSD image, which provided reliable data support for subsequent analysis.
Kevin (2025/07)
- Issue We Found:
During the MD simulation, the presence of metal ions in the protein complex caused instability in structure predictions. - Expert Advice:
Professor Kevin suggested we use AlphaFold3 for predictions and check the structural prediction results after adding manganese ions. - How We Improved:
Following Professor Kevin’s advice, we used AlphaFold3 to re-predict the complex structure and compared it with similar protein complexes in the literature. We ultimately determined the impact of metal ions on the model and optimized it.
Through the help of experts in the experimental group, we not only overcame the technical difficulties encountered in experiments but also received valuable guidance and support at every stage. From the provision of experimental materials to the optimization of experimental steps, and even the breakthrough of technical bottlenecks, each expert’s contribution greatly advanced the progress of our project. With their feedback, we continuously adjusted and improved our experimental design, ensuring that our research outcomes could reach high standards in both scientific rigor and practical application, thus contributing to innovation in the field of cancer treatment.
At the same time, the modeling group also achieved key breakthroughs under the guidance of experts. Whether it was the generation of RMSD plots or handling the stability of structure prediction involving metal ions, the modeling group gradually solved these problems under the advice of Professor Kevin. Through parameter optimization and structural reconstruction, they provided solid theoretical support for the entire project, allowing experimental data to be interpreted and validated more accurately.
It was precisely the dual advancement of experiments and modeling that enhanced our project in both theory and practice, ensuring the completeness and reliability of our research.
Safety and Feasibility Assessment
In the implementation of our project, safety and feasibility were two critical evaluation dimensions. To ensure the smooth progress of the project, we conducted rigorous reviews and assessments of both aspects from the outset.
Safety Assessment
Safety assessment was our top priority, especially with regard to the use of genetically engineered bacteria as a drug delivery platform. Since our research involves modifying microorganisms, we must ensure that the bacteria do not pose potential risks to the environment, patients, or other organisms.
We consulted with experts in the field, including Dr. Luo Ming, Deputy Director of the Oncology Department at Taihe Hospital, and Professor Tang Jianming from Lanzhou University, to evaluate our experimental design and research methods. Their feedback was very insightful, particularly highlighting issues related to immune responses and infectious risks. They reminded us to pay special attention to the safety of the modified bacteria to prevent them from causing adverse effects on the normal physiological systems of patients beyond tumor treatment.
Expert Recommendations:
Both Dr. Luo and Professor Tang pointed out that while the current delivery method is innovative, its safety still needs further verification. They suggested that we move the safety validation to the animal experiment phase in order to realistically simulate the drug’s behavior in vivo and assess its impact on organisms. This recommendation became the foundation for our subsequent safety validation and provided direction for future animal experiment designs.
We fully understand that safety assessment is not a static process but an ongoing one that evolves as experiments progress. Therefore, we decided to entrust the subsequent safety validation to future research teams, ensuring its long-term effectiveness and continuous improvement of the project.
Feasibility Assessment
The goal of the feasibility assessment is to ensure that our drug delivery platform can advance smoothly in terms of technical implementation, clinical translation, and social acceptance. Throughout this process, our team communicated with multiple iGEM teams, receiving valuable guidance and advice.
We had an online discussion with Sustech-Med, where we addressed issues within the project, particularly the challenges in technical implementation and clinical translation.
We particularly participated in discussions at CCIC, engaging with members from teams such as Yiye, CJUH-JLU-China, XJU-China, and Sustech-Med. These teams provided us with feedback on the feasibility of our project and supported us in the following areas:
- Project Design:
Several teams provided valuable advice on the technical implementation and clinical feasibility of our drug delivery platform, highlighting potential technical bottlenecks and optimization directions. - Technical Guidance:
In areas like bacterial engineering and drug delivery systems, members from other teams shared different experimental methods and research ideas based on their experiences, helping us optimize our experimental design. - Social Acceptance and Clinical Translation:
The teams also emphasized challenges regarding social acceptance, ethical issues, and clinical translation. They suggested that we engage in broader social communication to raise public awareness.
Through our communication with these teams, we received in-depth technical and social feedback, further confirming the technical path of our project and providing new ideas and more feasible solutions for our subsequent research.
Especially during the feasibility assessment phase, we had in-depth discussions with Professor Zhang Haibo and Researcher Wang Lei from Qingdao Institute of Bioenergy and Bioprocess Technology. They offered many constructive suggestions and directions for the project’s feasibility. They pointed out that although our drug delivery platform has great potential, there is still room for improvement. They proposed several feasible directions, such as:
- Drug Selection:
They suggested that we explore replacing the current drug with one more suitable for our delivery platform to enhance efficacy. - Combination Therapy:
They also recommended exploring the feasibility of using multiple drugs in combination, which could improve treatment efficacy and possibly reduce drug resistance issues.
The feedback from Professor Zhang Haibo and Researcher Wang Lei greatly broadened our perspective and gave us a deeper understanding of the project’s feasibility and future development direction. We will continue to incorporate their suggestions, exploring new drugs and treatment options to ensure the project progresses smoothly from a technical standpoint.
These communications and evaluations helped us further confirm the technical path of our project and provided new ideas for our subsequent research. Through close collaboration with various teams, we are more confident that, despite the technical challenges our project faces, it has strong feasibility for real-world applications.
In the upcoming work, we will continue to stay in close contact with other teams and experts to ensure the project progresses smoothly in all aspects, especially in technical optimization, clinical translation, and social acceptance. We believe that cross-team collaboration will lay a solid foundation for the success of the project.
Safety and feasibility assessments are key steps in ensuring the success of our project. Through feedback from experts and teams, we have clarified the direction of safety assessments and decided to leave the subsequent validation work to future research teams for further improvement. At the same time, the feasibility assessment has received support and guidance from multiple iGEM teams, particularly feedback from Professor Zhang Haibo and Researcher Wang Lei of Qingdao Institute of Bioenergy and Bioprocess Technology, which provided new feasibility ideas for our project. We are confident that, with more technical optimization and cross-team collaboration, our project will continue to evolve in a more feasible direction and ultimately bring innovative solutions to cancer treatment.
Education and Public Engagement
In our project, education and public engagement were not only aimed at popularizing synthetic biology knowledge but also at increasing societal understanding and acceptance of our research outcomes. Through various forms of educational activities, we interacted with students and the public of all age groups, gaining their feedback while continuously adjusting and improving our educational methods.
Educational Feedback and Improvement
In our educational activities, especially in the reading club, middle school teaching, and high school summer school sessions, we received many valuable suggestions from teachers and students. This feedback helped us continuously optimize our educational content and methods.
Feedback from the Reading Club:
In the elementary school reading club, we worked with Teacher Zhang Hairong and selected the ancient Chinese text “Liezi: Tangwen - Yanshi’s Creation of the Mannequin” to introduce the ethical issues of synthetic biology through classical biomimicry stories. While the class atmosphere was initially very lively, we found that directly diving into the explanation of the classical Chinese text made it difficult for children to connect the story to our project, resulting in less classroom interaction.
Teacher’s Suggestion:
Teacher Zhang Hairong suggested that before the lecture, we should first briefly introduce the iGEM competition background and our project content so that the students could better understand the story’s meaning and relate it to modern synthetic biology applications.
Our Improvement:
Following Teacher Zhang’s advice, in subsequent activities, we began with a brief introduction to the iGEM competition and our project background before introducing the ethical topics and cultural stories. This approach made the students’ understanding of the class content deeper, and the interaction became more active.
Feedback from the Middle School Teaching Session
In the middle school classroom we conducted in collaboration with Ms. Fang Yun, we designed a highly interactive teaching model. The classroom was full of Q&A sessions, and the students showed strong curiosity and enthusiasm, creating a very lively atmosphere throughout the lesson.
Teacher’s suggestion:
Ms. Fang Yun fully acknowledged the effectiveness of this teaching method at the middle school stage, but at the same time reminded us that this highly Q&A-dependent classroom model may not work well in higher grades. As students’ knowledge base and ways of thinking evolve, high school and above students need teaching designs with clear logical chains and gradually deepening content, rather than relying solely on interaction to maintain classroom effectiveness.
Our improvements:
Based on her suggestions, we placed greater emphasis on logical progression and knowledge structure building in subsequent teaching designs. While retaining interaction, we gradually added content arranged in a step-by-step manner, ensuring that higher-grade students could build a complete knowledge framework during interactions, rather than staying at the level of scattered Q&A.
Feedback from the High School Summer School:
In the high school summer school activity with Teacher Yongtao Zhu, we served as teaching assistants, helping students collect environmental bacterial strains and conduct Gram staining experiments.
Teacher’s Suggestion:
Teacher Zhu pointed out that the class should not only involve students’ hands-on activities but also stimulate their thinking. He suggested that we guide students to form hypotheses before the operation and help them establish a theoretical framework during the experiment to ensure that they connect practice with theory.
Our Improvement:
We adjusted the class design, and in subsequent lessons, this “operation-thought-summary” closed-loop approach significantly improved students’ depth of thinking and the quality of their questions. Students were able to better understand the principles behind the experiments.
Efforts to Improve Social Acceptance
To improve societal acceptance of synthetic biology, we actively participated in the “Smash the Myths of Synthetic Biology” manual project organized by CJUH-JLU-China. This activity brought together 33 iGEM teams, each proposing the myths they most wanted to dispel about synthetic biology, and refuting them with scientific evidence and vivid case studies.
Our Contribution:
In this activity, we collaborated with other iGEM teams to improve public understanding of synthetic biology, clarify misconceptions, and demonstrate the real applications and potential of synthetic biology through practical examples. We particularly emphasized the potential contributions of synthetic biology to medicine and environmental protection, interacting with the public through Q&A sessions, popular science articles, and other means to resolve their concerns.
Through our participation in this activity, we not only increased societal awareness of synthetic biology but also strengthened cooperation with other iGEM teams, forming a strong collective force to advance scientific development.
Future Education and Public Engagement
In the future, we will continue to invest more efforts in education and public engagement. We plan to bring more educational activities into communities and schools, especially targeting middle and high school students, through organizing more lectures, interactive experiments, and public science events to popularize basic synthetic biology knowledge to a wider audience.
Moreover, we will continue participating in similar social myth-busting activities to eliminate public misconceptions about synthetic biology through scientific explanations and data support, enhancing its societal acceptance and recognition.
Through educational activities and public engagement, we not only promoted synthetic biology education but also continuously refined our project through interactions with experts, students, and the public. We believe that only with the widespread support of science and society can synthetic biology truly fulfill its potential and benefit society. In the future, we will continue our commitment to education and public engagement, striving to improve societal awareness of synthetic biology.
Conclusion
Looking back at the entire implementation of the project, we have gained invaluable experience and lessons. Through in-depth communication with stakeholders, we have continuously optimized and improved our project in terms of safety, feasibility, education, and public engagement, ensuring the project can move forward steadily within the frameworks of scientific rigor, ethics, and social responsibility.
Our project not only focuses on solving the treatment challenges of triple-negative breast cancer but also aims to promote the popularization and social acceptance of synthetic biology technologies. Whether it’s through communication with doctors, cooperation with patients and researchers, or interactions with students and the public, we have always placed societal needs as the fundamental starting point of our project’s development, striving to ensure that our work truly serves society and benefits patients.
Through participation in CCIC, educational activities, and social myth-busting projects, we have not only increased societal awareness of synthetic biology but also strengthened public support and trust in our research. In this process, the support and help from experts, professors, team members, and the public have been the driving force for our continuous progress.
Although we have made significant progress, we know that the road to solving the treatment challenges of triple-negative breast cancer remains long and full of challenges. As the research continues to deepen, we will continue to optimize our drug delivery platform, explore new treatment pathways, and continually update and refine our safety and feasibility assessments. More importantly, we will keep focusing on patient needs, ensuring our research can transition from the laboratory to clinical settings, ultimately achieving precise, effective, and gentle treatment.
In the future, we will not only continue to work on scientific innovation in synthetic biology but also increase our investment in public education. Through collaboration with more teams and experts, we will promote the social application of synthetic biology technology and strengthen a comprehensive evaluation of its ethical and social impacts. We believe that with the dual drivers of technological progress and social responsibility, our work will bring good news to more patients in the future.
We look forward to seeing our research results enter clinical settings in the near future, providing more precise and effective treatment options for triple-negative breast cancer patients and contributing to innovation in the synthetic biology field.