In 2023, the iGEM team of the University of Macau, UM-Macau, aims to address gluten intolerance, as represented by celiac disease, by constructing a delivery-adhesion-release system for the duodenum. During this year's research in human practice, we realized that although this disease is a global epidemic, the distribution of the disease shows a clear trend of "less in the east and more in the west" - combining the characteristics of this disease with the fact that our team is located in Macau, where is a world-renowned tourist city and a center of cultural exchange between the East and the West, we are aiming to raise the awareness of the local population about the disease and to awaken the local community to a global vision of health care. At the same time, we are also working with different iGEM teams, experts, scholars, social figures, technology companies, relevant practitioners, and other stakeholders throughout the process of the project. In the past 5 months, we have conducted a series of external communications, participated in numerous meetups around the world, and played an important role as initiator, organizer and facilitator in several important alliances in similar fields or regions.

    The aim of our project is to help people suffering from gluten intolerance, as represented by Coeliac Disease, to free themselves from the potential health risks of long-term dietary restrictions and intestinal damage, so that people with Celiac Disease can live their lives as normal people under the protection of our project products - thus, the project title "GEIG: Gluten Enzymatic Intestinal Guardians" was developed based on the concept of "Guardianship" and other important elements. Therefore, based on the word "Guardians" and other important elements, the project theme "GEIG: Gluten Enzymatic Intestinal Guardians" was developed. Our mascot Wheatty, a magical little girl created from our engineered bacteria, will use synthetic biology magic as a weapon to safeguard the long-term intestinal health of everyone with celiac disease!

-Interview with Dr Zhang Jingwen

For clinical staff, we were fortunate to be able to have an interview with Dr. ZHANG Jingwen, a gastroenterologist at Kiang Wu Hospital in Macau, about UM-Macau's iGEM project this year. During the conversation, UM-Macau had a very interesting discussion with Dr Cheung about the prevalence of celiac disease in East Asia, common intervention strategies for food intolerance at the clinical level, and how to control the use of in vitro engineered bacteria for the treatment of intestinal diseases in a safer and more controlled manner. Dr ZHANG said that although the prevalence of celiac disease differs significantly between Eastern and Western countries, the idea that we want to enhance the local community's ability to care for foreigners and encourage more people with special needs to feel comfortable coming to Macau and contributing to the development of the local economy and culture through our project is very praiseworthy. At the same time, Dr Zhang also proposed the idea of temperature based kill switch to control the in vitro proliferation of the bacteria in the safety module built in our project, and this feedback has improved the overall design of our project later.

Figure 3.1.51 The photo was taken during the interview process with Dr.Zhang.

-Interview with Beer Pro

In today's world, gluten-free food supplies are an important part of life for people with celiac disease. To address the specific needs of celiac disease sufferers and to explore the importance of gluten-free food in Macau, we visited Beer Pro, a local shop selling gluten-free beer. During our face-to-face meeting with the merchant, we gained a better understanding of the recent development of gluten-free food in Macau - the merchant is unable to keep gluten-free beer in stock at all times due to cost issues; the gluten-free diet is not really widespread in Macau, and there is very little communication between the proprietors of Beer Pro and their friend merchants in Macau, which is certainly a big problem for celiacs traveling in Macau. The merchant expressed their support for the use of modified intestinal flora to address celiac disease, and believe that if the technology becomes widespread in Macau, it will enhance the ability of the Macau community to help celiac disease sufferers, help attract tourists to Macau, and contribute to Macau's economic development.

Figure 3.1.52/3.1.53 The photo was taken during the interview process with Beer Pro.

-Interview with Prof. Leung Lai Han

As a professor of the Faculty of Health Sciences of the University of Macau who has been involved in the research of intestinal flora in the past, Professor Leong Lai Han was also the subject of our interview. During the interview with Prof Leong, we discussed the cycle of probiotic drugs from R&D to practice, the dilemmas faced by intestinal flora research nowadays, and the public's views on genetically modified (GM) food. Professor Leung firstly expressed her approval of our project, saying that the choice of gut flora for the treatment of coeliac disease is a remarkable attempt! At the same time, Prof Leung also described to us objectively that intestinal flora as an independent research direction is still very young in the academic field, and a considerable part of the mechanism and process of its operation is still in a very vague state, but she also said that intestinal flora in the future there is still a very great potential for development, and encouraged us not to be backed off because of the difficulties. Finally, in the face of genetically modified products, Professor Leung said that we should look at this issue dialectically, and told us that as a research team we should popularize the relevant knowledge in a way that ordinary people can understand, and correctly help the public to build up a rational perception.

Figure 3.1.54/3.1.55 The photo was taken during the interview process with Prof. Leung.

-Interview and visit to ZHUHAI HENGQIN IMSTEM BIOTECH LTD

As an important part of our final transformation visit, the site visit to ZHUHAI HENGQIN IMSTEM BIOTECH LTD has provided us with a complete picture from R&D to production. Located in Zhuhai, Guangdong Province, IMSTEM BIOTECH LTD has only three floors, but it has all the essentials - it uses the first floor as its own R&D laboratory and the third floor as its own production workshop, which reflects the high efficiency and integration of the enterprise in production, learning and research. During this visit, we gained an in-depth understanding of IMSTEM BIOTECH LTD's research and development practices in the fields of anti-aging, medical aesthetics, and other products based on stem cells. In addition, the director of IMSTEM BIOTECH LTD highly praised the iGEM project of UM-Macau this year, and encouraged us to follow their model to improve the construction of the idea of industry-academia-research and patent application according to the similarity between the therapeutic track and the direction of the enterprise, so that our project can really benefit the world.

Figure 3.1.56/3.1.57/3.1.58 The photo was taken during the interview and visit process to IMSTEM BIOTECH LTD.

Analysis of Questionnaire Results

In our social research phase, we wanted to know more about the subject's knowledge of the core elements of our project in East Asia, synthetic biology, the perception of genetic engineering, and the attitudes towards the implementation of care for celiac disease as a specific group in East Asia, in order to further define our project's strategy to address celiac disease in East Asia, especially in China, and how to make the people change from not understanding about certain concepts to understanding about them, through our endeavors.

Figure 3.1.59/3.1.60 Collect questionnaires online.

After a long period of questionnaire collection, we collected more than 1,000 results from people of all ages and educational levels, from primary school students to middle-aged and older adults. From these results, we observed that 74.1% of the survey results came from people between the ages of 18 and 45, and 91.9% of the respondents had a high school education or higher.

Figures. The result of our online questionnaire.

In the first tier of questions, we investigated the preference for gluten-rich foods such as pasta and nuts in the East Asian region. The results showed that 67.6% of the population in East Asia had a preference for pasta, while 59.6% had a preference for nuts.

Figure 3.1.61/3.1.62 The result of our online questionnaire.

In the next question, we do surveys on the public about their knowledge of gluten, which is the core element of our project; And celiac disease, which is the target group of our project. The results showed that 65.8% of the population had no knowledge of the concept of gluten, while 53.9%, more than half, had never heard of celiac disease.

Figure 3.1.63/3.1.64 The result of our online questionnaire.

Combining these two questions we can draw feedback from the general public - from the level of understanding of "gluten" and "celiac disease" we can see that coeliac disease is not prevalent in our region, East Asia. Celiac Disease is not prevalent in our part of the world. The preference for gluten-rich foods such as pasta and nuts is at a high level here (especially in northern China), so for those in the West where Celiac disease is prevalent, traveling, studying and working in East Asia can be problematic for those populations. Next, a survey was conducted on the attitudes of the local population towards the special needs care of the migrant population and the results showed that 92.0% of the population felt that additional care for this population was necessary. At the same time, we also surveyed people's attitudes towards genetic engineering, and their knowledge of the synthetic biology tools for celiac disease that we used in the project, and found that there was an overall normal distribution of attitudes towards genetically modified products, but that up to 94.7% of the population had a relatively open attitude towards the use of genetically engineered pharmaceuticals. However, 71.8% of the respondents had no idea about the synthetic biology tools we used in the project.

Figure 3.1.67/3.1.68/3.1.69/3.1.70 The result of our online questionnaire.

Promotion to Our Project

Based on all the above feedbacks, we found that there is a clear contradiction between the vision of people with high prevalence of celiac disease in western countries who want to come to East Asia to work, live and work, and the lack of care and potential risks caused by the low prevalence of celiac disease and dietary habits here, which is in line with the hypothesis we made during the Brainstorm, and strengthens our determination to solve the problem. The contradiction between the public's lack of understanding of coeliac disease and synthetic biology and the passion for caring for special populations also made it clear that during the course of the project, education and popularization for the general public will also be the focus of our radiant influence on society. According to the results of the social research, the attitudes of a considerable number of people towards products related to GM technology are still negatively affected by the media publicity in recent years. Therefore, in addition to strengthening our investment in science education and helping to alleviate the public's misunderstanding about synthetic biology technology, enhancing the safety of the project must also be a key consideration throughout the project.

Overview

For a complete project, we, the UM-Macau team, will not only consider the short months of preparation for the iGEM in 2023, but more importantly, we will plan for a longer-term plan for our product, forming a complete R&D-production-practice closed loop. Therefore, in the final top-level design of the project, the thinking of industry-academia-research is also the key direction for us to get relevant feedback and new knowledge from the outside.

Enterprise Tea Party Form Communication

During our final translational exploration, we are fortunate to have four major research institutes and companies as our key collaborative partners: ZUMRI, Zhuhai Hengqin Imstem Biotechnology Co. Nanjing helptherapeutics Co., Ltd., Sanmedgene Co., Ltd. .With their help, we have been able to gain sufficient experience in entrepreneurship, R&D, production and practice from the enterprises, so that we can have a clear picture of the technology transformation level, and point out the direction for our next development after completing the development of the basic functional modules of the GEIG project. The partnership with these companies has allowed us to communicate with them directly——During August, in the form of a tea party, details of industry-academia-research and areas that UM-Macau should pay attention to in the future.

In their presentation to UM-Macau, the Representative of Sanmedgene Co., Ltd. emphasized the importance of in-depth academic knowledge and continuous study in the field of biotechnology, whether it is in the area of liquid cancer biopsy technology or celiac disease treatment. They hope that we can combine this "continuity" with the concept of project design cycle in iGEM to optimize our projects from the basic theoretical level.

Figure 3.1.71 Representative of Sanmedgene Co., Ltd. shared with us the experience of "Academia" in the context of industry-academia-research.

The representative of Nanjing helptherapeutics Co., Ltd. discusses with UM-Macau the aspect of collaborative research in the context of "research" in "industry-university-research". The representative of the company was very impressed by the cooperation between UM-Macau and many other iGEM teams this year in the construction of basic functional modules and human practice, and stressed that collaborative research is a very important way to improve the quality of research in the process of realizing the closed-loop of "industry-academia-research". They hope that we can maintain this spirit of cooperation in the process of patenting and putting our products into production in the future, and continue to realize the effect of 1+1 is greater than 2 together with different groups.

Figure 3.1.72 Representative of Nanjing helptherapeutics Co., Ltd. shared with us the experience of "Research" in the context of industry-academia-research.

Addressing the "industry" aspect of "industry-academia-research", the representative of Zhuhai Hengqin Imstem Biotechnology Co. In doing so, the representative of Imstem mentioned that the needs of the customer are a very important part of the actual industrial production. Combined with UM-Macau's strategic vision of "solving local problems" this year - UM-Macau was impressed by the lack of local care for celiac disease, dietary preferences that are not favorable to celiacs; And the fact that Macau, as a crossroads between East and West, attracts a large number of Westerners with high levels of celiac disease. UM-Macau has identified a potential blue ocean for its own project, which has the potential to grow the industry in the future, and encourages us to continue this strategic vision in future industry-academia-research transformations.

Figure 3.1.73 Representative of Zhuhai Hengqin Imstem Biotechnology Co., Ltd shared with us the experience of "Industry" in the context of industry-academia-research.

Field Visits - Exploring the Path to Patent Reality

In addition to the tea party, UM-Macau also visited Zhuhai Hengqin Imstem Biotechnology Co., Ltd in September again to study how a company specializing in biomedicine transforms its research into patents and ultimately products for the benefit of the public.

Figure 3.1.74/3.1.75 Zhuhai Hengqin Imstem Biotechnology Co., Ltd introduce their product’s research-product pathway.

In this field research, Imstem introduced to us the whole process of their latest product SCSRF from R&D to experimentation, to patent application and application. In this communication, UM-Macau had a clear understanding of how to apply for a patent and what the role of a patent is. And in response to our own project of treating celiac disease by building a delivery-adhesion-release system of gut microbiota, Imstem feedback us a clearer picture - since our product will be bacteria, similar to stem cell products, the development will take at least 5-10 years, patent application takes 1-2 years, and from the time it is put into practice to actually generating positive revenues will also take a relatively long period of time. Therefore, UM-Macau not only builds up a clearer view of the later stage, but also takes this opportunity to prepare for the later stage of long-term efforts in the GEIG project.

Figure 3.1.76 The patent of Zhuhai Hengqin Imstem Biotechnology Co., Ltd’s Product.