Integrated Human Practices

Integrated human practices is an important part of the iGEM competition, with special emphasis on the guiding role of practical activities on the experiments and the positive impact of the project on the society. This season, our interactions with experts and others focuesd on the theme of our project, using "ferroptosis" to treat cancer.

We incorporated the theoretical principles of engineering to establish the framework for our endeavors. Through an engineering lens, a project's life cycle typically encompasses phases such as planning, design and development, acceptance and maintenance management. In the context of an iGEM project, we segmented our undertaking into preparation, exploration and industrialization stages. Consequently, our integrated human practice involved conducting targeted activities during each phase, guided by this approach, and promptly incorporating the acquired insights into the overarching project design.

During the preparation stage of our project, we interviewed company representatives for suggestions on project selection, conducted surveys, community interviews, and other public investigations to understand the thoughts of the general public. We also interviewed non-profit social organizations to gather nationwide cancer data and interviewed psychology teachers to indirectly understand the psychology of cancer patients. All of these provided strong support for our project.

During the exploration stage of our project, in terms of the project implementation, we interviewed Prof. Guo, Prof. Qiao, Prof. Zhang, Dr. Li on the feasibility and some specific details of the project, who are experts in different fields of life science field. They put forward some practical suggestions and unexpected inspirations for the problems or puzzles we encountered during our experiment. Thanks to them, we had a clearer understanding of the design of the project and how to carry it out in the future. In terms of the social benefits of our project. What are the advantages of our program over traditional cancer treatments? What is the current clinical acceptance of using engineered bacteria for the treatment of tumors? And what else do we need to pay attention to if we want to produce the project and put it into clinical applications? To this end, we consulted the secretary general of Zhuhai Anti-cancer Association and interviewed Dr. Liu, Dr. Fan, Dr. Zhao, Dr. Jin, who are doctors with rich medical or clinical experience. Through the communication with experts, we have an in-depth understanding of cancer, including the incidence of cancer and the current clinical treatment methods.

During the industrialization stage of our project, we have explored the relevant policies of the biomedical industry, and need to be well-prepared for the future productization of our own project. Through communication with representatives from many companies, we are aware that we also need to further ensure the safety of the project, thus increasing the clinical applicability and providing higher possibilities for future clinical applications.

· Purpose

After the topic selection of our project, we are very eager to have experts who can evaluate the feasibility of our project and the potential for clinical application. Therefore, we found BERI PHARMA CO., LTD, which is established in 2015, is dedicated to applying advanced pharmaceutical technology, developing and producing specialty pharmaceutical ingredients, cosmetic ingredients and health care ingredients to provide professional empowerment solutions for customers with different needs. We invited Mr. Wang Yilin and a party, the main person in charge of the company, to visit our laboratory for communication and discussion.

· Details

Firstly, we presented our new project for this season to Mr. Wang, elucidating the conceptualization and preliminary design of the chosen topics. Mr. Wang and his colleagues acknowledged the project's innovation and furnished us with comparable products available in the market for analysis. They suggested that we develop the project with practical applications in mind, including considering the relative merits of our engineered bacterial therapy compared to other drug delivery methods. Mr. Wang informed us that there are already existing approaches in the market for treating tumor proteins through nanomaterials, thus prompting us to contemplate the competitive advantage of glucose oxidase mediated by engineered bacteria.

· Meanings

This exchange meeting has helped us realize the significance of industrialization during the brainstorming phase, leading to a more informed selection and finalization of projects. Mr. Wang encouraged us to strive in envisioning the display and assisted us in analyzing the potential for future development in the oncology industry. Unlike traditional small molecule drug delivery, our project has adopted an innovative approach to cancer treatment. If it can effectively reduce the high costs associated with conventional cancer treatment and enhance the targeting and safety of drug administration, it possesses significant potential to explore new markets in the future. Moreover, we discussed the potential of our approach to enhance targeted delivery and precision in inducing ferroptosis, compared to small-molecule tumor ferroptosis inducers. Ultimately, this exchange has laid the groundwork for closer collaboration in the future. Additionally, BERI PHARMA CO., LTD. has joined the ranks of active responders in the 1st iGEM Greater Bay Area Industry-Academia-Research Forum.

Prior to conducting the dissemination of cancer health knowledge, we distributed two separate questionnaires regarding the level of understanding of cancer to both domestic respondents in China and participants from other countries. These surveys aimed to investigate the general public's awareness of cancer-related knowledge. Based on the collected data, we have composed a report on the survey findings, which confirms the imperative need for educating the public about cancer-related knowledge.

· Analysis of Questionnaire Data from Chinese Respondents

As of October 1^st, 2023, we have gathered a total of 287 responses from the domestic questionnaire, primarily from individuals aged between 19 and 60, accounting for over 90% of the total number of completed surveys.

· Fundamental Knowledge of Cancer

Based on the questionnaire data collected, it was discovered that over 70% of respondents have a considerable understanding of various types of cancer. When asked about their knowledge of factors that can induce cancer, more than 60% of participants identified smoking, excessive alcohol consumption, unhealthy dietary habits, psychological stress, and obesity as contributing factors to individual susceptibility. Additionally, in regard to the contagiousness of cancer, 77% of Chinese respondents correctly believe that cancer is not infectious, demonstrating their fundamental knowledge on the subject.

Subsequently, we focused on investigating respondents' awareness of cancer treatment options. Over 60% of participants had heard of traditional treatment methods such as surgical excision, radiotherapy, and targeted therapy. However, there was limited knowledge concerning alternative treatment methods like traditional Chinese medicine treatment, biotherapy, and bacterial-driven therapy. Among these, respondents exhibited the lowest overall understanding of the bacterium-targeted tumor therapy utilized in this project.

Continuing our investigation, we conducted a survey among respondents regarding the bacterial-driven tumor therapy employed in the project. The data reveals that a mere 17% of participants believe in the effectiveness of this therapy, while 20% hold a pessimistic attitude, considering it incapable of achieving favorable treatment outcomes. Furthermore, about 60% of respondents either have limited knowledge or have never heard about this therapy, indicating a shallow and inadequate level of awareness and familiarity with the bacteria-driven therapy at present.

· Access to cancer-related knowledge

We conducted a survey on the channels through which the public acquires knowledge about cancer. The data reveals that over 50% of the respondents obtain information through the Internet and personal connections. Among these, mobile phones emerge as the primary medium through which respondents access information, accounting for 66% of the total number of respondents.

· Cancer prevention measures and attitudes

Regarding preventive measures against cancer, nearly 80% of the respondents believe that maintaining a balanced lifestyle and adopting a sensible diet can effectively prevent cancer. Additionally, nearly 70% of the respondents recognize that regular check-ups and nurturing a positive mindset are also effective in preventing cancer. This indicates that the majority of the respondents have a proper understanding of cancer risk factors and possess valuable knowledge of cancer prevention.

However, it is worth noting that despite the basic understanding of cancer among the public, we discovered that over 30% of the respondents undergo medical check-ups only once every 2-3 years, and 10% of them have never undergone any health examination. The primary reasons cited include lack of time to visit a hospital and the relatively high costs associated with check-ups. Furthermore, as the survey progressed, we also learned that most respondents estimate the cost of cancer treatment to fall within the range of one hundred thousand to one million units.

Lastly, it is crucial to acknowledge that nearly 40% of respondents harbor feelings of fear towards cancer. Thus, enhancing the dissemination of fundamental knowledge about cancer and its preventive measures could potentially alleviate the psychological burden experienced by the public.

· Analysis of questionnaire data from respondents from other countries

As of October 1, 2023, we have collected a total of 158 questionnaires from various countries around the world. The respondents represent diverse regions and the age range is predominantly concentrated between 19 and 60 years old, accounting for approximately 90% of the total number of participants.

· The basic knowledge related to cancer

When asked about their understanding of cancer risk factors, the highest percentage of respondents, nearly 80%, believed that excessive obesity could lead to the development of cancer. Approximately 50% of the respondents recognized that smoking, excessive alcohol consumption, unhealthy diets, and lack of exercise can also contribute to cancer. Furthermore, around 40% of the respondents from other countries believed that cancer is contagious, indicating a relatively shallow understanding of basic cancer-related knowledge among the survey participants.

Moving on to the investigation of cancer treatment options, almost 60% of the respondents had heard of traditional treatment methods such as surgical removal, radiation therapy, and targeted therapy. However, similar to the respondents from China, they lacked knowledge about alternative treatments such as traditional Chinese medicine, biotherapy, and bacterial-driven therapy. Among these, the understanding of bacterial targeted tumor therapy, which is the treatment method employed in this project, was found to be the lowest.

Furthermore, we conducted a survey specifically targeting the bacterial targeted tumor therapy used in this project. The data reveals that over 65% of the respondents held a negative attitude, either perceiving the treatment as ineffective or lacking sufficient knowledge about it. This indicates that the popularity and understanding of bacterial targeted therapy are relatively limited and not well-established.

· Seeking Channels for Cancer-related Knowledge

Regarding the channels through which the general public obtains cancer-related information, data reveals that mobile phones are the primary means of accessing information, accounting for 67.7% of the total respondents. Additionally, approximately 62% and 55% of individuals acquire information through personal connections and television, respectively.

· Preventive Measures and Attitudes towards Cancer

In terms of preventive measures against cancer, over 80% of respondents perceive regular check-ups as an effective means of prevention. Approximately 64% of respondents believe that a well-balanced diet can effectively prevent cancer, while more than 40% recognize that maintaining a positive mindset and balancing work and rest are also effective methods of prevention. However, concurrently, over 30% of respondents still undergo check-ups only every 2-3 years. Furthermore, when asked if they hold any fear or anxiety toward cancer, 74% of respondents acknowledged experiencing varying degrees of apprehension.

· Summary

Upon analyzing the two sets of data obtained from conducting surveys in both China and other countries, it can be observed that the majority of respondents in both surveys fall within the age range of 19 to 60 years. These individuals typically utilize modern tools like mobile phones and television to obtain information about cancer, demonstrating their critical thinking skills and ability to gather basic information. They serve as valuable samples for assessing the general level of cancer knowledge in society. The survey results align with our expectations and validate empirical conclusions regarding the dissemination of cancer knowledge. This data provides a realistic foundation for implementing the project and underscores the societal value of addressing cancer.

Both groups possess a certain level of basic knowledge about cancer. However, compared to the respondents in China, those from other countries display a relatively weaker understanding of cancer-related information. This indicates a need for increased cancer education initiatives in these regions.

In terms of cancer treatment approaches, respondents had the lowest level of understanding about the bacterium-targeting tumor therapy utilized in this project. This highlights the necessity for further public promotion of the effectiveness of bacterium-based treatments and specific treatment plans. The aim is to enhance public awareness and encourage more patients to consider adopting effective and cost-efficient bacterial-driven tumor therapy.

Furthermore, the majority of respondents demonstrate a correct understanding of cancer risk factors, and the general population possesses good knowledge of cancer prevention. However, a significant portion of respondents still do not take preventive measures.

Finally, the overall attitude towards cancer among the public tends to be negative. This emphasizes the importance of disseminating cancer-related knowledge to promote a more positive perspective.

· Purpose

To learn about the incidence rates of cancer, disparities between urban and rural areas in terms of cancer prevalence, the sources of carcinogens and other facts helping us estimate the future productization and provide strong evidence to carry out education activities. Therefore, we interviewed Weixiang Sun, Secretary General of Zhuhai Anticancer Association. The association mainly conducts research on comprehensive cancer treatment, rehabilitation medicine and anti-cancer drugs, carries out anti-cancer business exchanges, and edits cancer-related materials and journals. We hope to contact them to better understand the local cancer incidence and treatment status.

· Details

Mr. Sun showed us the National Cancer Center’s latest issue of national cancer statistics released in February 2022. Combining with this statistic, he told us that the incidence of malignant tumors and the number of deaths from cancer in China keep rising. And the annual medical expenditure due to malignant tumors exceeds 220 billion yuan. The differences between rural and urban areas in terms of diet, environment, lifestyle and other factors, results in difference in cancer incidence and death rates between urban and rural populations.

At the same time, they are the pioneers of cancer science popularization in urban areas. He gave us some suggestions on activities of public engagement. The key to education is to let people understand that we are the first ones responsible for our own health. Also, he suggested that our background research of tumor can start from the “Three Mouths” (“三张口”) of cancer (“癌”), i.e., drinking, eating and breathing, and base on the changes of food culture, environment, work and life, etc.

· Meanings

Through insights gained from this interview, we have developed a greater understanding of the continuous significance of cancer as a crucial health issue. This understanding has further reinforced our drive to tackle this project and effectively contribute to finding solutions to combat cancer. Additionally, the interview has provided beneficial insights and information that directly shape our approach to education and awareness initiatives. For example, this interview has motivated us to initiate a subsequent community awareness campaign. Specifically, we intend to base on the facts proposed by Dr. Sun, to promote the correlation between daily routines and cancer, and to enhance people's understanding of wholesome lifestyles.

· Purpose

We talked with social workers in each of the three villages while conducting science education. These social workers had greater awareness of local cancer incidence and cancer treatment and the economic burden on local residents. Our aim was to better comprehend the local cancer situation through the detailed experiences shared by the on-site staff, in order to establish a basis for future science education endeavors.

· Details

We first introduced our purpose and what we wanted to know. We talked with these social workers about the familial clustering of some cancer diseases, and compared the differences of cancer incidence between urban and rural areas. In talking to social workers in the three villages, we found a common problem: not only the lack of medical resources in rural areas, but also the inadequate dissemination of cancer informaion. In addition, many older adults do not value early cancer screening, prevention, and treatment. We also know that cancer often brings a heavy burden to the family and even the society. In many cases, once the cancer is detected, it is already at an advanced stage, which brings endless pain to myself and my family. The current cancer treatment has a long cycle and high cost, and there is an urgent need for a new cancer treatment reform.

· Meanings

After reviewing the issues identified during our campaign, we understand that there is still a great need to raise awareness and promote cancer prevention, early screening, and treatment in our community. Therefore, it is necessary to improve overall cancer awareness, promote the concept of early detection and early prevention, and encourage older people to seek treatment. At the same time, we found that the elderly often have a negative view of cancer, and the current treatment cycle and cost of cancer bring a serious burden to cancer families. We hope that our project will truly solve the deficiencies and challenges faced by traditional cancer treatment in the future.

·Purpose

In previous investigations and research, it was found that the journey from cancer diagnosis to treatment and rehabilitation is a lengthy process that not only leads to physical changes in patients, but also evokes strong emotional and psychological responses. The treatment of tumors is highly challenging, resulting in significant financial burden for patients and their families, as well as imposing a substantial psychological weight on patients. Additionally, cancer patients frequently experience various psychological disorders. If these disorders are not effectively treated, they can negatively impact a patient's motivation for tumor treatment and the overall effectiveness of the treatment.

To enhance the care provided to cancer patients, we have invited Dr. Hejing Zhang, a lecturer specializing in cognitive neuroscience at Beijing Normal University's Zhuhai Campus. Dr. Zhang teaches courses such as Health Psychology and possesses expertise in understanding the cognitive neuroscience, thereby contributing to our comprehension in this field.

· Details

During our online interview, Dr. Zhang provided us with valuable information about cancer patients. He spoke about their psychological traits, how stigma affects them, ways to confront stigmatization, social support, and ways to care for them.

It is known that cancer diagnoses often elicit strong emotions such as anxiety, depression, anger, fear, and sadness. Emotions can change during treatment, and they might increase slightly during the initial diagnostic and diagnostic stages.

Stigma could discourage patients from seeking genuinely useful medical assistance or support, so it merits greater attention. We can assist cancer patients in conquering shame by offering professional counseling and treatment, providing them with objective education, and reinforcing social support. For instance, we can encourage patients to join cancer support groups and other social activities where they can share their experiences and emotions with other cancer patients. This helps build stronger support networks.

Dr. Zhang supported our program's efforts to care for cancer patients during treatment. He also mentioned that training healthcare professionals to improve their understanding and response to the psychological needs of cancer patients can be beneficial.

1. Characteristics of the psychological state of cancer patients:

Question: In your observations and practice, what are the common psychological characteristics and reactions that appear in cancer patients? How do these characteristics develop and evolve during the treatment process?

Answer: Cancer diagnosis often evokes intense emotional reactions in patients, including anxiety, depression, anger, fear, and sadness. These emotions may fluctuate to varying degrees during different stages of treatment, but generally tend to peak during the early stages of diagnosis and treatment. The fear of uncertainty, characterized by a lack of knowledge regarding the progression of the disease and the effectiveness of treatment, represents a commonplace source of ambiguity. Consequently, this uncertainty can engender long-term anxiety and feelings of tension. Furthermore, the treatment process can give rise to changes in self-perception, such as hair or weight loss, which can profoundly impact a patient's self-esteem and confidence.

2. The impact of illness-related shame:

Question: How does a sense of shame play a role in the psychology of cancer patients? What kind of impact does it have on their emotions, self-esteem, and social activities?

Answer: Feelings of shame can often arise among cancer patients, resulting in emotions of guilt, inferiority, and a sense of unworthiness regarding their care. This is especially true when cancer is linked to specific lifestyle habits or cultural stigmatization. Shame can impede patients from actively seeking appropriate medical assistance or support out of a fear of others discovering their cancer diagnosis. Moreover, these sentiments can also have an impact on patients' engagement in social activities and intimate relationships, ultimately leading to feelings of loneliness and isolation.

3. Methods to overcome illness-related shame:

Question: Have you ever found any effective methods to help cancer patients overcome feelings of shame in your practice? Could you please talk about it from the aspects of psychological counseling, social support, education and information transmission.

Answer: There are several ways to alleviate feelings of shame:

Psychological counseling and therapy: Professional therapy can help patients address shame, enhance self-esteem and confidence. Treatment often includes cognitive-behavioral therapy and emotional support.

Education and information dissemination: Healthcare professionals should provide detailed information about the disease to help patients better comprehend and cope with cancer. Education can reduce unnecessary fears and misunderstandings.

Social support: Support from family and friends is key. They can encourage patients to share their feelings, express emotions, and provide practical help and companionship.

4. The importance of social support:

Question: The social and family support is crucial for the psychological well-being of cancer patients. How do you think we can build and maintain such a support system? What specific advice can be provided to patients and their families?

Answer: Support from family and friends should be warm, understanding, and unconditional. They can assist patients in coping with daily challenges, provide emotional support and solace. Participating in cancer support groups and social activities can help patients establish additional support systems, where they can share experiences and emotions with other cancer patients. The medical team also plays a vital role by providing professional knowledge and care. They should listen to patients’ needs, answer questions, and establish a relationship of trust.

5. Recommendations for caring for the psychological well-being of cancer patients:

Question: What specific suggestions do you have for how medical personnel, family members, and the general public can better care for and support the psychological well-being of cancer patients?

Answer: - Healthcare workers should receive training to better understand and address the psychological needs of cancer patients. They should establish a close doctor-patient relationship and provide warmth, respect, and support.

- Family members and the general public should avoid treating cancer patients in a negative way, avoiding discrimination and stigmatization. Understanding and empathy are crucial.

- Patients themselves should actively engage in psychological therapy, interact with support groups, and learn to manage their emotions. Accepting one's own emotions is an important first step.

· Meanings

Through this interview, we gained a comprehensive understanding of the typical psychological characteristics of cancer patients. We're now more committed to treating cancer by not only addressing its physical symptoms, but also providing psychological support to patients. We believe that healing both the body and mind together will help patients recover faster, experience less pain during treatment, which can achieve better humanistic care.

· Purpose

Identifying a project requires careful consideration and consultation with experts to identify a truly meaningful and achievable project. Through prior communication within the team, we initially selected the project on this topic. However, in the project improvement stage after the assignment, we still have many questions about the design of some modules, and we want to consult relevant professors to improve the project. Therefore, we conducted an in-depth interview with Prof. Zhong Guo, an associate professor at the Biotechnology Research Center of Beijing Normal University. Prof. Guo mainly researches and develops multifunctional nano-adjuvants targeting immune-related cells to prepare nano-vaccines for the prevention and treatment of tumors.

· Details

After introducing our project, we consulted Prof. Guo about the efficient expression of the RGD motif peptide, achieving magnetic orientation of chemically modified Fe₃O₄ onto the surface of engineered bacteria, the tumor tissue-specific promoter SUR promoter, engineered bacteria-mediated production of H₂O₂ in cancerous tissues, the Fenton reaction, and engineered bacteria-mediated silencing of the GPX4 gene in tumor cells. Prof. Guo gave us professional advice on our questions. For example, the RGD sequence can be designed to be chimerized with the nanocarrier, which makes the nanocarrier have the function of tumor targeting based on the original advantages. Also, he suggested that before colonizing the tumor site with magnetically guided engineered bacteria, the depth of magnetic field penetration in human tissues should be taken into consideration to prevent selecting tumor types that are too deep. For further areas of the project, Prof. Guo recommended that the team focus on refining the targeting of the genetically modified bacteria and ensuring the project's safety.

· Meanings

Through discussions with Prof. Guo, the team acquired a thorough comprehension of the project design involving engineered bacteria that mediate ferroptosis, along with a clearer vision for project follow-up and enhancement. For example, in our subsequent project design, we adopted Professor Guo's suggestion and abolished the method of displaying the RGD motif to bind αvβ3 and αvβ5 integrin on the surface of tumor cells by engineering bacteria expressing outer membrane protein OmpA. We continued to search for more specific and accurate targeting methods in the following days. Also, after communicating with Prof. Guo, we recognized the necessity of obtaining expert advice from diverse research fields and improving the project step by step to establish a solid theoretical foundation and enhance the project's quality for subsequent experiments.

· Purpose

After discussing with Prof. Guo, we found that talking with experts can provide us with practical suggestions and unexpected inspirations. At the same time, we realized that if we wanted to refine this program, we would need to consult some experts in cancer research. Therefore, we decided to interview Prof. Yongkang Qiao, an associate researcher at the Biotechnology Research Center of the Institute of Advanced Natural Sciences, Zhuhai Campus of Beijing Normal University. Prof. Qiao's research focuses on new tumor diagnosis and treatment target molecules and their mechanism of action, including tumor microbial colonization and the mechanism of participating in the occurrence and development of tumors, which is relevant to our project.

· Details

First of all, our team introduced the background of the project, gene circuit design, and safety to Prof. Qiao. Prof. Qiao listened carefully to the specific content of each link and discussed with us the process of engineering bacteria to achieve cancer treatment.

The first discussion was about the ferroptosis sensitivity of tumor cells. Prof. Qiao believed that heterogeneity is one of the important characteristics of malignant tumors and a significant reason for the development of cancer drug resistance. Prof. Qiao also believed that different types, grades, and stages of tumors will affect the effectiveness of cancer treatment, so the project needs to consider whether all tumor types are more sensitive to ferroptosis. Based on the information we have obtained, including kidney cancer, pancreatic cancer, diffuse large B-cell lymphoma, liver cancer, breast cancer, colorectal cancer, and cancer cells that have acquired drug resistance, we conclude that a variety of cancer cells are sensitive to ferroptosis, but the main pathways of ferroptosis regulation may be different in different cancer cells.

Then Prof. Qiao inspired us to think, since our engineered bacteria function in multiple modules, how can we be sure that the engineered bacteria can actually express the corresponding substances to function? After discussing with the professor, we realized that when verifying the effectiveness of therapy, we need support from qualitative or quantitative experimental data that can verify the effectiveness of therapy. At the same time, we also need to consider how to more accurately and conveniently understand the effect of engineered bacteria in vivo after the product is put into practical application. Therefore, we considered how to further improve the detectability of engineered bacterial therapy.

· Meanings

Prof. Qiao provided us with valuable and expert insights on our project's design and experiments. Her suggestions helped us clarify our doubts and address the project's shortcomings. For instance, based on her experience, she advised us on means to enhance the experiment's accuracy and rigor. Moreover, she recommended that we consider the clinical utility of the project further while ensuring simplicity and safety in the therapy.

Finally, Prof. Qiao encouraged us to collaboratively communicate and discuss the project with appropriate medical professionals. She kindly offered to provide assistance in reaching out to expert oncologists so that we can enhance our understanding of the ongoing clinical treatments and research in oncology. This knowledge will facilitate continuous project improvement and ultimately enhance our ability to provide relevant and effective care for patients.

· Purpose

After the interview with Prof. Qiao, she introduced us to Dr. Zhigang Liu, helping us understand the current status of clinical tumor treatment and establishing the groundwork for future clinical implementations of the project.

· Details

Firstly, our team members briefly introduced the project design to Dr. Liu. After a clear introduction to our project, we asked Dr. Liu a series of questions about the clinical background, significance, and feasibility of the project.

In terms of the clinical development of the project, we consulted Dr. Liu about whether the in vivo anti-tumor biological vectors could be well promoted and applied in clinical practice compared with small molecule clinical reagents. Dr. Liu believed that all drugs and designs need strict clinical trials before application, such as phase I, phase II, and phase III clinical trials, to continuously evaluate their safety and therapeutic effect. Only through the validation of the efficacy and safety of these clinical trials can they be promoted and applied in clinical practice. In the process of in vivo anti-tumor biological vector drugs from experiment to clinical application, first of all, the safety of the drugs needs to be ensured, and secondly, the effectiveness of the drugs needs to be ensured, and the potential of large-scale clinical application of the drugs needs to be evaluated. In addition, in reality, it is also necessary to consider whether the drug production has a reasonable process, whether the drugs can be transported under appropriate conditions, and other issues.

· Meanings

In this interview, Dr. Liu shared his extensive experience in scientific research and clinical practice to discuss the current status of common tumor treatment modalities in the clinic. He provided insights into their actual efficacy, identified current problems, and introduced new therapeutic modalities along with their prospects for clinical application. Additionally, he highlighted various factors that should be considered when designing drugs and therapeutics from scientific research to clinical application. Dr. Liu also offered guidance and suggestions on how to address patients' needs and realize the clinical significance of the project.

This interview has motivated us to conduct further interviews with pharmaceutical companies and community residents. Our objective is to obtain a comprehensive understanding of the productization approach and public demand, aiming to enhance the project development chain from the front end, middle, and back end.

The First Interview

· Purpose

After the first few expert interviews, we refined the project based on expert recommendations. After updating the project, we had many questions about the engineering bacteria mediating ferroptosis. As a novel ferroptosis mediator, our engineered bacteria have many different properties compared to traditional small molecule ferroptosis inducers. So we turned to Prof. Xiaotian Zhang for help, a professor at the School of Life Sciences at Beijing Normal University.

· Details

After listening to our project introduction, Prof. Zhang mainly discussed the following issues with us. Firstly, the targeting of engineered bacteria, that is, whether engineered bacteria can accurately target tumor tissues and reduce the possibility of off-target damage to the body; second, the impact of engineered bacteria on normal tissues, that is, whether its presence in the body will have side effects on normal tissues; third, the impact of engineered bacteria on the body itself, which needs to consider that excessive use of engineered bacteria may have adverse effects on the body. Therefore, Prof. Zhang suggested that we design relevant experiments by consulting the literature, such as designing different gradients, to determine the safe dose of engineered bacteria. Prof. Zhang believes that when considering the treatment of tumors with engineered bacteria, it can be compared with conventional drug treatment. When these engineered bacteria are used in the treatment, the above three issues are worth our careful consideration.

At the same time, Professor Zhang reminded us to set up a negative control in the experiment to verify that the ferroptosis of tumor cells is due to the role of the bacterial transformation module and has nothing to do with bacterial invasion. We can also supplement some biomarker detection related to ferroptosis and consider designing different MOI gradients for infection experiments, so as to provide more support for the data. We accepted Professor Zhang's proposal and later tested the infection effect of different infection ratio MOI in the validation experiment of some modules in the experiment. At the same time, we used the ferroptosis inhibitor Fer-1 treatment as a control to reveal the occurrence of ferroptosis.

· Meanings

Prof. Zhang reminded us that we need to pay special attention to the safety of the project and also gave us some suggestions on the productization of the project. From this interview, we realized that we need to focus on the efficiency of the effective pathway and also improve the safety of the product in order to promote the productization of the project. This led us to conduct interviews with pharmaceutical companies. At the same time, Professor Zhang gave us a lot of guidance in the experimental design, and we adopted many of his suggestions in the later experimental development, which ensured the credibility of the ferroptosis verification experiment.

The Second Interview

· Purpose

After the first interview, we refined the program. However, in the later experiments, we encountered many problems in the module of engineered bacteria-mediated RNAi silencing of SLC7A11. We hoped to consult Prof. Zhang again about the selection of ferroptosis targets, so we conducted a second interview with her.

· Details

During the interview, we discussed the selection of specific targets with Professor Zhang. Professor Zhang elucidated the intricate relationship between the level of SLC7A11 expression and tumor cell sensitivity to oxidative stress. According to Professor Zhang, cells with a high level of SLC7A11 and glucose deficiency will accumulate an excessive amount of disulfide in cystine, leading to disulfide stress. This excessive disulfide stress will result in an increase in disulfide bonding in the actin cytoskeleton, causing contractions and structural breakdown, ultimately leading to cell death. Additionally, we explored how reducing the activity of the SLC7A11 gene can induce glucose starvation. This aspect is significant as our project involves genetically engineering bacteria to produce glucose oxidase and create a glucose-starved environment.

Moreover, Professor Zhang introduced us to the concept of disulfidptosis, which is a distinct form of cell death compared to ferroptosis. She recommended that we analyze the presence of SLC7A11 in tumor cells and detect the occurrence of disulfidptosis after delivering glucose oxidase into the tumor cells using engineered bacteria.

After a lengthy discussion lasting approximately one and a half hours, we concluded that our primary aim, whether it be inducing ferroptosis or disulfidptosis, is to eliminate tumor cells. Based on the current study's findings, silencing SLC7A11 can induce ferroptosis, therefore confirming that there are no issues with our project itself in terms of inducing ferroptosis by silencing SLC7A11 in tumor cells.

This interview provided us with a greater understanding of the SLC7A11 module within our project. Consequently, we now have a clear direction for further experimental enhancements, enabling us to evaluate the efficacy of the pathway more effectively. Furthermore, the interview validated the feasibility and accuracy of our experimental design. Consequently, we compiled the detailed suggestions provided by Professor Zhang, which will serve as a guide for further improvements to the shRNA-SLC7A11 module of our project. Moving forward, we will continue to assess the impact of this cross-kingdom RNAi system on other ferroptosis target genes.

· Purpose

Traditional Chinese medicine (TCM) is a repository of the experiential and theoretical knowledge derived from ancient Chinese people's battles against diseases. Developed over centuries of medical practice, TCM is a comprehensive theoretical system. TCM's external therapy has gained significant importance in tumor treatment and care, encompassing actions such as direct tumor eradication, alleviating cancer-related pain, managing toxic side effects following radiotherapy and chemotherapy, and preventing and treating postoperative complications. Within this context, living biological therapy is an integral component of TCM. We sought to interview doctors proficient in TCM treatment to solicit their feedback on our project. So we interviewed Dr. Yingri Zhao.

· Details

Dr. Zhao explained the differences between Chinese and Western medicine in their treatment approaches. Chinese medicine aims to harmonize the entire body system to address the underlying causes of diseases, whereas Western medicine primarily targets specific diseases to achieve quicker results.

By providing an example of integrating traditional Chinese medicine and Western medicine in cancer treatment, Dr. Zhao emphasized the differing perspectives on the healing process and the role of TCM in treatment. Dr. Zhao revealed that cancer patients frequently experience significant pain and adverse symptoms, including dizziness, nausea, and loss of appetite, following each chemotherapy session. TCM endeavors to augment the efficacy of Western medical treatments while mitigating their side effects.

In the context of our project, Dr. Zhao underscored the importance of prioritizing safety in accordance with TCM principles. He recommended considering how drugs impact the overall bodily system and their potential for effective metabolism. Consequently, meticulous attention to drug design and administration methods is essential. Dr. Zhao also highlighted that an increasingly common factor contributing to the rise in cancer among younger individuals is the prevalence of unhealthy lifestyle habits. For example, poor dietary choices can significantly elevate the risk of colon cancer.

During the discussion, we learned about the traditional Chinese medicine principle of "fighting poison with poison," where substances like scorpions, centipedes, and toads have been employed in cancer treatment. This historical concept of "immunity" bears some resemblance to our use of attenuated Salmonella typhimurium in tumor treatment. Although the toxic side effects of the engineered bacteria are reduced after attenuation, they can still stimulate the body's immune response and recruit immune cells to attack tumor tissue.

· Meanings

This interview yielded valuable insights. We gained an understanding of the genuine experiences of cancer patients during treatment and the side effects and limitations associated with current cancer treatments. Moreover, we were reminded that our project should prioritize designing for enhanced efficiency and reduced pain compared to existing treatment methods, emphasizing the importance of the safety module.

Additionally, the interview brought to light that one of the contributing factors to the increased incidence of cancer among younger individuals is the prevalence of unhealthy lifestyle habits. This insight has motivated us to plan community outreach activities aimed at raising public awareness about these detrimental habits and promoting a healthy lifestyle to reduce cancer incidence.

· Purpose

During previous discussions with several professors and doctors, it became apparent that our project must address safety concerns, such as the targeting of engineered bacteria and the therapeutic impact of VNP20009 once introduced into the human body. To gain further insights from frontline clinicians regarding our project, we collaborated with the JLU-NBBMS team to connect with Dr. Lifang Jin, an experienced doctor specializing in oncology clinical treatment. Our intention was to interview Dr. Jin to assess the clinical feasibility of our project and the acceptance of engineered bacteria by frontline doctors. Additionally, we sought to gain a deeper understanding of the current clinical treatment of tumors through these interviews.

· Details

Dr. Jin graduated from the Department of Clinical Medicine at Jilin University (formerly Bethune Medical University) and has been engaged in clinical work since graduation. With more than 9 years of clinical experience, he has a wealth of knowledge in the diagnosis and comprehensive treatment of various hematological systems and malignant tumors. With his professional medical knowledge, Dr. Jin helped us analyze the safety, targeting, and characteristics of the engineered bacteria in our project. He listened patiently to our experimental results and provided many valuable suggestions.

This season, we have many similarities with the JLU-NBBMS team in terms of the selected chassis cells and project design, so we jointly interviewed Dr. Jin and consulted with him. At the beginning of the meeting, we briefly introduced our project design. Doctors then focused on the safety and targeting of our project and raised questions. The first topic was the discussion of the chassis cells we have selected. Dr. Jin had doubts about the anti-tumor function of attenuated Salmonella. We discussed several aspects, beginning with the ability of bacteria to enhance human immunity against tumors. We learned from the discussion that cellular immunity is an important immune killing mechanism, and attenuated Salmonella can interact with the host as a pathogen and mediate killing by activating the inflammasome pathway and inducing the production of lymphoid T cells. At the same time, Dr. Jin introduced the causes of tumor immunotherapy commonly used in clinical practice, compared with the recruitment of immune cells mediated immune killing by attenuated Salmonella, and analyzed its feasibility. Meanwhile, we discussed that attenuated S. typhimurium is an intracellular parasite and can partially mediate autophagy in tumor cells, as shown in previous studies.

During the meeting, we naturally moved on to discussing project targeting. Dr. Jin emphasized the significance of precise targeting for both project safety and clinical applicability. According to him, although attenuated S. typhimurium can selectively colonize hypoxic tumor areas, this alone is inadequate. Dr. Jin informed us that hypoxic tissue does not necessarily equate to tumor tissue, emphasizing the need to enhance engineered bacteria's ability to colonize tumors beyond their intrinsic properties. We presented our approach of targeting tumor cells by expressing Lpp-OmpA-scFv and anchoring scFv to the surface of our engineered bacteria. Dr. Jin acknowledged the specificity achieved through antigen-antibody interaction as promising but suggested exploring more specific targets like HER2.

· Meanings

The interview meeting with Dr. Jin provided valuable insights into critical aspects of your project that require further refinement to enhance its clinical applicability. The experiences and feedback from frontline clinicians underscored the importance of prioritizing safety and targeting in your project.

Dr. Jin's encouragement and positive outlook on your project's potential in the field of targeted drug delivery were reassuring. He acknowledged the promise of engineered bacteria as vectors for delivering therapeutic proteins or nucleic acid drugs to patients in the future, particularly in comparison to the anti-tumor effect of attenuated S. typhimurium alone. However, his caution regarding potential adverse reactions resulting from the introduction of engineered bacteria into the human body highlights the need for meticulous safety considerations.

Dr. Jin's thorough review of your experiments related to scFv functionality and his suggestion to initially co-cultivate normal and tumor cells to confirm bacterial infection selectivity reflect the importance of robust experimentation and validation. Furthermore, the proposal to explore animal tumor kinetic models in the future to assess the enhanced targeting capabilities of engineered bacteria upon scFv expression demonstrates a commitment to rigorously testing and improving your project.

· Purpose

During the verification process of our project, we faced significant challenges in achieving prokaryotic expression of engineered bacteria. These difficulties arose due to our limited experimental knowledge and lack of operational expertise. Specifically, the module involving glucose oxidase secretion by VNP20009 posed several problems that perplexed our experimental group members. As a result, we sought assistance from Dr. Li, a postdoctoral researcher at the Biotechnology Research Center who possesses extensive expertise in detecting prokaryotic expression systems.

· Details

We presented our project to Dr. Li and provided a detailed explanation of our design for expressing glucose oxidase using the type III secretion system in attenuated Salmonella typhimurium VNP2009, as well as its delivery to tumor cells. Dr. Li commended our project idea and encouraged us to verify the normal functionality of the type III secretion system through protein level verification. However, in our initial experiments, we encountered difficulties in obtaining tumor cells for Western blot verification after co-culturing the transformed engineering bacteria. The Western blot did not reveal any specific bands of the correct size. Dr. Li assisted us in analyzing the experimental process in depth, including operational details and irregularities. One important point raised by Dr. Li was the tendency of prokaryotic engineering bacteria to form high-density insoluble protein particles (inclusion bodies) enclosed in membranes when expressing foreign proteins. This often leads to misfolding of the target protein, resulting in loss of activity and subsequent functional verification issues. During our discussions, we identified a potential risk of fusion between the foreign gene and the type III secretion system's SopE peptide, which could impede the proper folding of the target protein due to the lengthy SopE sequence. Dr. Li informed us that to enhance the solubility of exogenous proteins expressed by engineered bacteria and prevent the formation of inclusion bodies, the cultivation conditions for these bacteria may need to be more intricate. Therefore, we should conduct further gradient experiments to explore and ascertain the most suitable conditions.

· Meanings

Through this interview, we gained more knowledge about prokaryotic protein expression. Dr. Li carefully helped us to analyze the difficulties encountered in the experiment and gave us solutions.

Finally, we found that at 37℃, we realized that inclusion bodies may form in VNP20009. Inclusion bodies are high-density (1.3 mg/ml) insoluble protein particles encapsulated by membranes when foreign genes are expressed in prokaryotic cells. According to the advice from Dr. Li, we adjusted the bacteria culture temperature to 30℃. (For more information:Engineering)

To enhance communication among iGEM teams and facilitate the integration of the synthetic biology industry, academia, and research in the Greater Bay Area, our team BNUZH-China, along with UM-Macau, HKUST, and SZU-China teams, collaborated to organize the first iGEM Greater Bay Area Synthetic Biology Industry-Academia-Research Forum (referred to as the 1st iGBA) on August 19th and 20th this year at Beijing Normal University at Zhuhai.

As one of the most concentrated regions globally for iGEM teams and biotechnology-related high-tech industries, several iGEM teams from the Greater Bay Area, including UM-Macau, HKUST, SZU-China, and BNUZH-China (representing Universidade de Macau, The Hong Kong University of Science and Technology, Shenzhen University, and Zhuhai campus of Beijing Normal University, respectively), have joined forces to explore innovative modes of collaboration between iGEM teams and industry. The primary objective of this collaboration is to promote university-industry cooperation and facilitate the cooperative growth of the biotechnology industry cluster in the region. To kickstart this initiative, the 1st iGBA Forum brought together academia and enterprises from the Greater Bay Area, serving as a nucleus for fostering collaborative partnerships in research and development. During the opening ceremony, Songlin Shi, a member of the Conference of China iGEMer Community (CCiC) Presidium, emphasized that scientific research exchange between teams is a crucial aspect and a valuable outcome of the competition. Furthermore, he expressed support for collaboration and communication among all parties in the Greater Bay Area, recognizing the potential it holds.

· Workshop

Industry-Academia-Research Salon
During the session of Industry-Academia-Research Salon, representatives from four industry companies, namely Kairui Biotech, ZHUHAI SANMED BIOTECH, Help Therapeutics, ImStem Biotechnology shared their respective research achievements and collaboration experiences in the field of industry-academia-research partnership. (Click on the card below to learn more)

1. Kairui Biotech
Kairui Biotech specializes in researching, producing, and providing technological services in mammalian cell culture media. The company supplies serum-free media for diverse cell types and purposes, offers recombinant protein preparation and stable expression cell line construction services, and provides contract research and development services for cell therapy products. The company's technical team consists of scientists who have years of experience in new drug development in large international pharmaceutical companies and fundamental medical research in world-renowned research institutions.

During his lecture, Jun Wu, the company representative, emphasized four important aspects of translating biological research achievements into actual product production: "from complexity to simplicity," "from simplicity to complexity," "technology-driven," and "assisted by luck."

From his lecture, we gained the following insights. Firstly, although the process of technological development is intricate, the ultimate objective is to create safer products with more stable quality and lower costs. Therefore, it is crucial to consider the significance of product development from this perspective. Secondly, in the field of pharmaceutical development, technological progress is built upon advancements in basic technologies in order to develop more practical and efficient drugs. We should explore how to create more effective drugs for the human body based on the current foundation of scientific development, such as formulating multi-component remedies for the common cold.

Thirdly, the development of biotechnology necessitates the support of various technical backgrounds from multiple disciplines. Thus, assembling a team with multidisciplinary talents is essential during the technological development process.

Lastly, he emphasized the importance of observing life phenomena or experimental results, summarizing experiences, and achieving product innovation.

Overall, these points highlight the importance of a comprehensive approach in translating biological research achievements into successful product production.



2. ZHUHAI SANMED BIOTECH
ZHUHAI SANMED BIOTECH is an innovative precision medicine company that has mastered the world's leading liquid biopsy technology for tumors. The company focuses on the development and industrialization of liquid biopsy reagents, automated equipment, and artificial intelligence cloud computing for major malignant tumors such as lung cancer, breast cancer, and liver cancer. Currently, the company's products have established clinical collaborations with over 100 top domestic and international hospitals.

Jinglu Zhang, the company representative, provided an in-depth overview of the significance and value that the company's pioneering solution for early diagnosis of lung cancer through liquid biopsy holds. He emphasized the integration of synthetic biology and high-tech innovations to contribute to the realization of China's national strategy for a Healthy China. Through his presentation, we gained an understanding of the paramount importance of innovation and a systematic approach in product development. This encompasses not only the advancement of cutting-edge technologies but also the establishment of a comprehensive business operation system for innovative products. This entails various stages such as technology introduction, iterative innovation, product development, and large-scale manufacturing, ultimately leading to the commercialization of these products. Furthermore, this process relies heavily on government policy support, capital accumulation, and talent recruitment.



3. Help Therapeutics
Help Therapeutics is a globally leading innovative therapy development company specializing in regenerative medicine for incurable age-related diseases. It serves as the pioneer in constructing China's iPSC cell model repository for incurable diseases and has established multiple intelligent platforms. The company continuously focuses on the development of innovative therapeutic products for degenerative diseases such as the cardiovascular system. Through its exclusive patented technology in cell culture solutions, it enhances differentiation efficiency and reduces upstream cell production costs. With the integration of the Help Cell-foundry mass production platform, the company consistently strives to create safe, effective, quality-controlled, and affordable treatment products for patients.

Ying Xuan, the company's representative, highlighted the national "Fourteenth Five-Year Plan" key project and various collaborative initiatives related to the standardization and application of the human iPSC-derived cell repository. She emphasized the principle of "utility-oriented and open sharing" in the collaborative efforts between academia, industry, and research in synthetic biology. By anchoring the forefront of precision medicine, leveraging technological innovation as the driving force, and ensuring high-level talents, the company aims to strengthen its advantages in platform, technology, resources, and attract more innovative and high-quality elements to promote the integration and innovation of the biopharmaceutical industry in the Guangdong-Hong Kong-Macao Greater Bay Area.

Through her lecture, we comprehend the importance for companies to intensify communication with major universities and hospitals, deepen collaboration between industry, academia, and research institutions, and enhance efforts in key technological breakthroughs to facilitate the transformation of scientific achievements.



4. ImStem Biotechnology
ImStem Biotechnology is a high-tech enterprise and original pharmaceutical company with patented cutting-edge technologies in the fields of stem cells and regenerative medicine. It has emerged as a representative example of overseas talent and excellent projects introduced in the Hengqin Island (Zhuhai)-Macao in-depth cooperation zone. The company is approved by the Ministry of Human Resources and Social Security of China as an independent recruiting unit for postdoctoral researchers. It has also been recognized as part of the Guangdong Province's "Pearl River Talent Program" for attracting leading talents and has obtained certifications as an innovative and entrepreneurial team, unicorn seed company, and new research and development institution in Zhuhai City.

Yusheng He, the company's representative, introduced the pioneering research in the field of stem cells, highlighting the breakthrough achieved through the collaborative efforts of industry, academia, and research institutions. These efforts have resulted in the establishment of three scientific and academic platforms, namely the targeted differentiation of human embryonic stem cells, autologous pluripotent stem cells, and stem cell gene editing and modification technologies. He further discussed the transition of these research platforms from the laboratory to clinical and industrial applications.

We realize that in the field of biomedicine research, entrepreneurship must collaborate with universities, clinical institutions, and other stakeholders to establish a multi-center scientific and clinical cooperation network. This serves to facilitate the application of research and its outcomes.



5. Dr. Fan from Science, Technology and Economic Development Bureau of Zhuhai High-tech Zone
Dr. Fan holds a Ph.D. in Intellectual Property from the University of Science and Technology of China, a Ph.D. in Management from University of Science and Technology Beijing, a postdoctoral degree in Business Administration from Beijing Normal University-Hong Kong Baptist University United International College (UIC), and a postdoctoral degree in Finance from the Chinese Academy of Social Sciences. He currently serves as the Director of the Administration Committee of Zhuhai High-Tech Zone. With extensive experience in the field of economics, he has a deep understanding of biopharmaceutical policies and expedited approval processes. Furthermore, he has conducted long-term research in the field of industrial finance, specializing in areas such as IPOs, angel investments, and venture capital.

Dr. Fan provided insights into collaborative models and effective approaches in the industry-academia-research partnerships in synthetic biology. He introduced the new collaborative approach known as "license in" and "license out," stressing the significance of considering industry perspectives to foster successful cooperation. Additionally, Dr. Fan delved into the industrial policies associated with synthetic biology, highlighting the regulatory policies and trends adopted by different countries in this field. In terms of recommendations for industry-academia-research collaboration in synthetic biology, he examined the market differences between China and the international context. To illustrate this point, he shared the example of joint laboratories established in the Guangdong-Hong Kong-Macao region, encompassing diverse research areas. Moreover, Dr. Fan emphasized the current state of capital markets and company developments, suggesting that the integration of academia-industry-research communities and the establishment of innovative companies could potentially serve as a merger strategy for listed companies, thereby facilitating the transformation of technological industries through fresh perspectives.

University-Enterprise Exchange Session
During the university-enterprise exchange session, we set up booths together with iGEM teams and enterprises to promote cooperation between industry, university and research institutions. The aim is to facilitate the practical application of iGEM research projects in industry. The participating iGEM teams included BNUZH-China, SZU-China, HKUST, HKU, SUStech-Med, HongKong-CHUK, SYSU-SLS-China, SCIE-PearlDelta, HKSSC. In the afternoon, we gave full play to the advantages of the interactive form of the booth, and the participating teams, participating enterprises and guests had in-depth understanding and communication with the enterprises and other teams they were interested in. At the same time, iGEM teams and enterprises prepare their own publicity materials such as culture and innovation, posters and so on to assist communication. The participating teams introduced their own projects, listened to the reports of other teams, and exchanged opinions and suggestions to further understand the feasibility and difficulty of the transformation of iGEM projects.

· Enterprise Visit

1. BYHEALTH
BYHEALTH is a leading brand and benchmark enterprise in the field of dietary nutrition supplements in China. By implementing a scientific nutrition strategy and leveraging modern nutritional science, it has established a comprehensive scientific system for dietary nutrition supplements. It collaborates with global cutting-edge research capabilities to continuously carry out scientific research on nutrition and its intervention in chronic diseases, with an unwavering commitment to scientific excellence and the creation of top-quality nutritional products.

The BYHEALTH Transparent Factory, completed in June 2012 in Zhuhai, Guangdong province, serves as a technologically advanced and stringent quality-controlled production base for dietary nutrition supplements. With a design featuring transparent glass, the factory enables traceability of global raw materials and transparent production processes. Moreover, the company adopts an honest and open approach, inviting various sectors of society to visit the Transparent Factory and witness the quality of raw materials and the entire production process.

During enterprise visit, we first traveled to the BYHEALTH Transparent Factory, where we were able to witness the development and production processes of world-class quality products up close. Inside the Transparent Factory, we witnessed the nutritional ingredients and additives from 23 countries and regions around the world through the transparent glass. These raw materials and additives undergo modern, high-standard, and scientific research, production, testing, packaging, and other core processes to become high-quality products. After visiting the intelligent factory, we followed the guide to the Nutrition Exploration Hall to learn relevant knowledge about healthy nutrition.

This tour of the BYHEALTH Transparent Factory deepened our understanding that intelligent production is the future trend in manufacturing. Enterprises should continuously innovate by integrating technology into their production processes and developing their own intelligent production lines.Additionally, an effective supply chain is crucial and indispensable for the product's success. Enterprises should prioritize effective supply chain management and establish a systematic and competitive model that covers everything from product sourcing to final delivery.



2. ZHUHAI UM SCIENCE&TCHNOLOGY RESEARCH INSTITUTE
ZHUHAI UM SCIENCE&TCHNOLOGY RESEARCH INSTITUTE is an exemplary hub for academic-industrial collaboration established by the University of Macau in the Greater Bay Area. Leveraging the research capabilities of three national key laboratories and prominent disciplinary institutions at the University of Macau, the institute boasts five research and development centers and one business training center in the Hengqin Island of Zhuhai. Through the construction and development of this demonstration base, it will serve as a vital hub for scientific innovation cooperation, promoting the integration of Macau into the national development framework, synergizing technological and innovative elements between Macau and the mainland, and consolidating international cutting-edge innovation resources. Additionally, it will facilitate the transformation and upgrading of industries in the Greater Bay Area by offering a platform for the conversion of scientific and technological achievements.

During our subsequent visit to the ZHUHAI UM SCIENCE&TCHNOLOGY RESEARCH INSTITUTE, the staff diligently acquainted us with the institute's development history, significant accomplishments, and future prospects. They led us on a comprehensive tour of the laboratories, showcasing state-of-the-art experimental equipment. We acquired numerous novel research ideas and witnessed the exciting projects and achievements in the realm of scientific inquiry.

Through this visit, we not only gained an understanding of the vibrant research platform, but also experienced firsthand the thriving vitality of academic-industrial collaboration in the Greater Bay Area. We firmly believe that the practical implementation of such collaborative endeavors will bring about even more positive impacts to society.



With the continuous realization of cutting-edge achievements in synthetic biology, more and more universities and enterprises in the Guangdong-Hong Kong-Macao Greater Bay Area strive to be the leader of synthetic biology industry. However, how to achieve the "two-way rush" of science and industry is not only a problem faced by the iGEM team, but also a problem that needs to be considered in urban development.

As one of the most densely distributed regions of global bio-related high-tech industries, the cooperation of the iGEM teams from four universities in the Guangdong-Hong Kong-Macao Greater Bay Area has opened up a new way of iGEM team cooperation. With the linkage between universities and enterprises as the core of the forum, the two important innovation poles and growth poles of universities and enterprises in the Guangdong-Hong Kong-Macao Greater Bay Area have been gathered to build a bridge for industry-university-research cooperation and promote the cooperation and development of the bio industry group in the Bay Area. We believe that as a synthetic biology competition, the projects should not only stay in the laboratory, but need to have more discussions and exchanges with the scientific research industry, and fully evaluate the market value of the project and the difficulty of achievement transformation.

Through this activity, we have access to the latest cutting-edge technology, communicated with the upstream and downstream enterprises related to the project or similar enterprises, and gained a deeper understanding of our project. We eagerly anticipate the continued growth and development of the iGBA Conference, as it not only inspires future iGEM teams in China but also fosters academic collaboration and mutual prosperity in the Greater Bay Area. By doing so, the conference will make a significant contribution to the economic advancement of the region.

· Purpose

After consulting with experts, it has been ascertained that industrialization serves as a pivotal factor in the success of any project. In order to enhance our comprehension of this matter, conducting interviews with industry representatives proves to be beneficial. Consequently, an interview was conducted with Mr. Jun Wu, the esteemed CEO of Zhuhai Kairui Biotechnology Co.

· Details

Mr. Wu initially presented his personal professional background and entrepreneurial journey, highlighting the importance of the entrepreneurial team's comprehension of industrial production processes within the organization. Moreover, he pointed out a notable disparity between conducting research projects and establishing a pharmaceutical production company, specifically in terms of prioritizing cost reduction and revenue enhancement to maintain financial support for the research and development endeavors. Furthermore, he exemplified this notion by referencing his company's product, the serum-free culture medium, which underscored that the advancement of novel technologies could originate not only from extensive fundamental research but also from identifying preexisting issues. After we presented our team's project, he inquired about some information regarding our project and emphasized the following key points: (1) the need to strengthen targeting, ideally by establishing animal models or referencing relevant literature data to determine if our drug development might have off-target effects and what side effects they might cause; (2) the need to enhance safety, suggesting conducting experiments to verify the metabolic duration of bacteria within the body, as the prolonged survival of bacteria could pose potential risks; (3) the need to explore the reproducibility of drug research. He also mentioned that to further improve various aspects of the project, it is advisable to have researchers with different specialties working together in the team. They also recommended interviewing more experts to understand how other industries operate outside the laboratory.




Towards the end of the interview, he enthusiastically led us to tour different areas of their company, including the office space, laboratory area, and shipping area, providing us with a brief overview of each area's layout, functions, and their interconnections. Additionally, he emphasized the importance of safety in both laboratory research and industrial production.

· Meanings

This interview provided us with project advice from the perspective of the pharmaceutical industry. We also gained preliminary insights into the industrialization direction of our project. In the upcoming experiments, we will place a greater emphasis on safety and incorporate more considerations for industrialization into our experimental design. For example, we will conduct experiments on how drugs are metabolized within the body to enhance their metabolic capabilities.

This interview has given us valuable recommendations that will help us transition our project from academic research to industrialization. In subsequent experiments, we will prioritize safety and infuse industrialization thinking into our experimental design process. On one hand, we will strengthen research on the metabolism of drugs within the body to further understand their processing, thereby improving their metabolic efficiency and safety. This will contribute to ensuring the rational use of drugs in the body and reducing potential risks.

Furthermore, we will incorporate more industrialization considerations into our experimental design. We will focus on the industrial production and commercial application of drugs to ensure the scalability and economic viability of our experimental results. We will pay closer attention to factors such as cost, efficiency, and process optimization, aiming to achieve better industrial feasibility.

The insights acquired from this interview will compel us to prioritize safety and industrialization in our experimental design and project development. We will incorporate the company's recommendations into our project's specific requirements, thereby paving the way for the achievement and industrialization of our project.

· Purpose

During our discussions with experts and companies, we have realized the importance of transforming projects into products. We have also gained valuable insights into the processes and considerations involved in productizing projects. As a result, we aim to further explore the relevant policies of Zhuhai's biomedical industry to be well-prepared for the future productization of our own projects. So we interviewed Dr. Tuoyuan Fan.

· Details

In our interview, we divided our discussion into two main categories: policy and financing. First, we asked Dr. Fan about the current status of Zhuhai's biomedical industry, with a focus on the policy aspect. According to Dr. Fan, the biomedical industry is one of the major industries in Zhuhai, and the government has implemented several supportive policies. Dr. Fan specifically discussed the government's policies for supporting innovation and entrepreneurship, as well as those for promoting innovation and creativity in tumor treatment. We learned that the Zhuhai government has established a comprehensive financial support system for the biomedical industry, particularly in the area of tumor treatment, with specific policies to support its upstream, midstream, and downstream development.

We also consulted with Dr. Fan regarding his expertise in industrial financing. Dr. Fan recommended that, in order to secure investment more efficiently, the project should address key challenges within the industry. Additionally, he emphasized the importance of the team leader having a clear understanding of the project and a wealth of experience and expertise. Dr. Fan also provided us with information on the various financing channels available and explained their different focuses on the project. He further advised on the optimal timing for project financing.

· Meanings

Through this interview, we gained valuable insights into the strategies employed by the Zhuhai government to foster innovation and entrepreneurship. This has bolstered our confidence and prepared us for the next stages in implementing our project. Furthermore, we greatly benefited from Dr. Fan's extensive expertise in financing, which has helped us avoid unnecessary detours in the subsequent product development process and enhance both its efficiency and success rate. This interview has provided us with a substantial amount of new knowledge, leading us to recognize that the success of a project hinges not only on having exceptional biological knowledge but also on diligently working towards effective management and financial practices.