Before the Project Pnitiation: Feasibility Study on Concepts and Schemes

Policy Guidances: Promoting the Design of Foods with High Folate

The "big food concept" was first proposed at the 2015 Central Rural Work Conference of China. As an important concept put forward by General Secretary Xi Jinping, the "big food concept" emphasizes expanding from traditional food security to a diversified food supply system. Its core is to "obtain calories and protein from farmland, grasslands, forests, oceans, as well as plants, animals and microorganisms", and meet people's increasingly diversified nutritional needs through comprehensive development of food resources. The nutritional, diversified, personalized and customized characteristics of food consumption demand are becoming increasingly evident, which also puts forward new requirements for food production and supply. Currently, a new round of agricultural technological revolution driven by biotechnology and information technology is on the verge of major breakthroughs, with countries worldwide making comprehensive plans for key technologies like gene editing, synthetic biology, and microbiomics. By establishing and practicing the concept of diversified food sources, we can speed up the development of a science and technology innovation system that matches food production needs, and work to overcome bottlenecks in crop varieties, technologies, and equipment. We can further expand agricultural development space through modern agricultural science, develop a wide range of food varieties, and ensure the stable and safe supply of grain and important agricultural products.

For daily folate supplementation, the World Health Organization (WHO) recommends 0.4-0.6 mg per day and emphasizes that red blood cell folate levels should be at least 400 ng/mL. The United States generally recommends 0.4 mg/d, though actual intake can reach 0.8-1 mg/d under certain food fortification policies. From pre-pregnancy to early pregnancy, China advises a daily folic acid supplement of 0.4-0.8 mg, with 0.4 mg/d to be continued during the middle and late stages of pregnancy. Canada follows the same standards as the WHO and also suggests supplementation through folate-fortified foods. Thus, given the current trends in food health and safety development in China and globally, it has become a reality we must seriously address to apply synthetic biology methods and technologies in promoting the production and supply of personalized, diverse, and customized foods with high folate content.

Doctors' Advice: Emphasizing the Necessity of Supplementing Active Folate Through Food

To explore effective ways to supplement folate, we interviewed doctors at the Guangdong Women and Children Hospital. The doctor stated: "Ordinary synthetic folic acid is very cheap, with a 10-yuan bottle lasting a month, making it the top choice for most people. But if there are genetic metabolism issues, switching to active folate becomes necessary, and it costs much more." "In our country, pregnant women now generally know to take folate supplements, so severe deficiencies are rare. Middle-aged and elderly people, however, need more attention—insufficient folate and high homocysteine levels are hidden drivers of cardiovascular and cerebrovascular diseases." "We definitely recommend MTHFR gene testing. Once moderate to severe mutations are detected, active folate should be used immediately with the dosage increased."

To further understand how medical and health services work in low-income areas, and whether folate supplement by diet can be accepted by the public, detailed interviews were conducted with staff at Dayukou Town Health Center in Zhaoqing City, Guangdong Province. It was learned that primary healthcare focuses on the health of pregnant women and elderly residents, by providing folate supplements to women of childbearing age, free prenatal check-ups during pregnancy, and postnatal health follow-ups for mothers and infants. However, primary medical institutions face heavy workloads and staffing shortages. If residents could get enough nutrients through their daily diets, it would help lower the number of chronic disease visits and ease the pressure on medical services.

During visits to low-income farming households in Dayukou Town, Zhaoqing City, Guangdong Province, it was found that local residents have limited knowledge about daily folate supplementation. Additionally, the relatively high cost of commercial folic acid products further restricts their folate intake. However, getting folate from daily meals is a more acceptable approach for people.

Enterprises and Farmers’ Requirements: Expecting High-Folate Soybeans to Increase Production Value

To explore the potential market value of high-folate soybeans, we visited the Fuzhu Factory in Dayukou Town, Zhaoqing City, Guangdong Province. The factory has selected soybean varieties that thrive in the local climate and successfully developed high-value-added products like selenium-enriched Fuzhu through research collaborations. It has also adopted innovative technologies to enable efficient grinding of soybeans and full release of active proteins, which has significantly enhanced the nutritional quality and commercial value of its soybean products. The person in charge of the factory showed strong interest in high-folate soybean raw materials, noting that such products could further meet people's needs for healthy eating and hold great potential market value.

Meanwhile, we visited the Village Committee of Guantan Village in Dayukou Town. Guided by the deputy director of the committee, we toured local soybean farms and talked with several growers and villagers. The town enjoys a good ecological environment with little pollution, which helps produce high-quality agricultural products. Right now, the key tasks are to combine scattered farming practices, set up reliable sales paths, bring in simple processing projects to raise the value of farm products, and actually increase farmers' earnings. Local farmers mentioned they hope to grow high-folate soybeans while keeping their traditional farming and management methods as much as possible. But they also want related departments to handle the purchasing support properly.

Scientist Suggestions: Feasibility and Safe Controllability of Genetically Modified Plant Design

To get a clear picture of how genetically modified plants are currently developed and promoted, and to check if our plan works, we had in-depth talks and learning sessions with scientists in the field. According to these scientists, using transgenic technology to make high folate soybeans through biosynthesis is not only doable but also aligns with the current trends in science and social development. They also noted that the technologies involved in designing genetically modified plants are quite mature, and the systems for testing and regulating genetically modified plants and food safety are well put in place. So, as long as we follow the related rules when running the project, the whole design will be reasonable and under control.

Professor Lin Qiupeng from the College of Agriculture, South China Agricultural University, is an expert in plant gene editing who has conducted extensive research on constructing efficient plant genetic transformation vectors and developing transformation procedures. He provided us with several valuable suggestions: transgenic strategies can be gradually replaced by gene editing, and editing backbones can be isolated through progeny screening to prevent transgenic residues. Since folate degrades easily at high temperatures, attention can be focused on non-high-temperature processed soybean products such as natto and fermented soya beans. These products are typically processed at temperatures ranging from 60-80°C, resulting in a folate retention rate of over 50%.

Professor Wang Shengbin, Executive Deputy Director of the Testing Center for Environmental Safety Supervision of Plants and Plant-Using Microorganisms under the Ministry of Agriculture and Rural Affairs at South China Agricultural University, specializes in environmental safety testing of genetically modified plants and component analysis of genetically modified plants and their products. Professor Wang explained the essential stages involved in developing and promoting genetically modified plants, and highlighted the physical isolation strategies needed during their cultivation. This helped us understand that strict adherence to regulations is necessary throughout the creation of genetically modified plants.

Professor Zhu Qinlong from the College of Agriculture at South China Agricultural University is an expert in plant synthetic biology. He has conducted extensive research on developing common genetic engineering technology systems (including multi-gene stacking systems, genome editing systems, and general genetic engineering technologies) and applying them in plant metabolic engineering and synthetic biology. His work includes creating new multi-gene stacking systems and broad-targeted multiplex base editing systems, and he was the first to successfully synthesize anthocyanins and the advanced carotenoid astaxanthin in rice endosperm. Professor Zhu spoke positively about our project, noting that using synthetic biology to boost nutrients in food crops will become a key approach in future agriculture. This method will significantly improve people's ability to get essential nutrients they need. He also highlighted that many successful examples already show synthetic biology's potential for developing high-value agricultural products, adding that our project is truly workable.

iGEM Gold Medal Instructor’s Comments: How to Build an Excellent Team

Professor Chen Gu from South China University of Technology, who won the iGEM Gold Medal as an instructor in 2017, applies multi-omics technologies to research and develop functional foods, nutritional factors, and fermented foods, while also investigating microalgal stress response and signal transduction mechanisms. Since our project aligns closely with Professor Chen's research focus, we sought her advice on project design and team building. Professor Chen emphasized that a project needs unique innovative aspects, requiring the ability to spot opportunities others might overlook in ordinary situations. She noted that our project has a good starting point, which makes it even more important to work hard to achieve its goals. Additionally, she reminded us to strengthen coordination between different groups, ensuring their work as a unified whole. Team members should support each other, as only through collective effort can the project succeed.

Project in Progress: Ensuring Efficient Experimental Procedures and Safety

Safety Training: The Cornerstone of Laboratory Safety

The wet lab experiments of our project were mainly conducted at the Laboratory of Plant Reproductive Development and Soybean Germplasm Innovation, College of Life Sciences, South China Agricultural University. Before starting the project and throughout the experimental process, we had multiple discussions and learning sessions with Professor Wang Cong, the laboratory safety officer. These interactions helped ensure our operations met laboratory safety standards, and we also promptly shared this information and supervised the members of the wet lab team. The safety training covered several key areas, such as handling engineered bacterial strains, disposing of waste bacterial solutions and plates, operating high-speed centrifuges and metal baths, managing solid and liquid waste, and responding to emergencies. These training sessions helped us successfully finish the planned experimental projects.

Experiment Experience: Optimizing the Soybean Genetic Transformation Process

Soybean genetic transformation is a time-consuming experiment with many complex steps. It involves handling explants, mixing plant hormones in the right proportions at different stages, and following strict rules for using ultra-clean benches. To make sure the experiment went smoothly, we first asked for advice from Li Xiaohao, a PhD student who manages the lab's genetic transformation platform. We also got in touch with Weimi Company, which focuses on plant genetic transformation. Together, we confirmed many details like choosing the right soybean genetic background, getting explants to sprout and grow roots, and planting and selecting positive seedlings.

Equipment Training: Setting up Folate Extraction and Detection Methods

Extracting folate from dry soybean seeds and testing its active ingredients is a key part of our project. To ensure smooth progress, we reached out in advance to the technician managing the HPLC-MS system at South China Agricultural University's Testing Center. During the training, we clarified the instrument's detection principles, confirmed the required buffer pH and environmental temperature for folate extraction, and finalized the selection and testing protocols for folate standards. These preparatory efforts significantly boosted the workflow efficiency of the wet lab team members.

Model support: Professional advice for model designing

Model designing based on structure biology and biosynthesis is one of the most important tasks for our dry group members. In order to ensure these work going smoothly, we organized interviews with Professor Jia Qian and Tian Yifu from South China Agricultural University, they are experts in the field of plant protein structure biology and biosynthesis. They gave us lot’s of useful suggestions about how to adjust parameters when using AlphaFold3 for protein structure prediction, how to decide the interaction between enzymes and their substrates, and how to select proper elements during bioengineering. What’s more, we also organized interviews with Professor Huang Peijie from South China Agricultural University and iGEM ambassador Li Zixi to get help for natural language processing and model development. These HP activities support the model designing work efficiently.

Project Enhancement and Extension: A Strong Connection from Laboratory to Society

Popular Science Popularization: Multi-faceted Science Popularization for Different Groups

A variety of science popularization activities have been organized to promote the concept of biosynthetic high-value-added agricultural products, and enhance understanding of folate and personal nutritional health among different populations. On the one hand, our booths were set up on up to 5 occasions at events including campus science festivals, community science festivals, and theme garden parties. Through on-site questionnaires, distribution of promotional brochures, fun mini-games, and on-site lectures with Q&A sessions, biosynthetic technology and daily folate acquisition were introduced to diverse groups. These groups included campus teachers, students, faculty children, and community residents of various ages and occupations. On the other hand, more than 10 popular science articles were published on the team's official WeChat public account using convenient online resources, with a cumulative view count reaching 1,500.

Specialized Education: Targeted Education for Specific Groups

To achieve targeted publicity and education, we designed distinct activities for primary and college students. For fifth-grade classes at Tangshu Primary School and Western Wheat Field Primary School, we introduced fundamental synthetic biology concepts, organized hands-on experiments (DNA extraction) to deepen understanding, and held creative art sessions. These art activities included writing about new products invented through synthetic biology and designing paintings of synthetic biology-themed mascots. These efforts helped students better understand synthetic biology and sparked their interest and enthusiasm for biology. Student participation was extremely high, and their mascot designs provided us with valuable inspiration for our team's mascot.

Meanwhile, an interdisciplinary debate competition titled "Is Patent Protection for Gene-Edited Microorganisms Appropriate" was held on our university campus. The event aimed to break down disciplinary barriers and encourage college students to think deeply about the ethical, legal, and social issues in synthetic biology innovation. It focused on popularizing knowledge of gene editing and patents, fostering critical thinking and multi-perspective analysis skills, and helping the audience understand the complex trade-offs in technological development. The competition attracted students from various majors and received an enthusiastic response.

Industry-University-Research: From the Laboratory to the Field and Factory

To promote the integration of industry, academia, and research, and move our project from the lab to actual production, we carried out a series of in-depth surveys in Dayukou Town, Zhaoqing City, Guangdong Province. First, with guidance from local government officials, we gained an understanding of the government's plans and overall strategy for developing modern agriculture. Second, we took part in soybean planting in the fields. Led by Professor Guo Changkui from the College of Life Sciences at South China Agricultural University, we learned about scientific soybean planting methods and seedling care techniques. At the same time, we visited local Fuzhu processing plants to find out more about how companies source soybean materials and their export markets. Finally, we went into farmers' homes to learn about their real needs. This made us think about what kind of benefits the project could bring to farmers and businesses if it were used in real production.

Frequent Collaborations: Interaction and Integration Between Project Practice and Campus Culture

During the project implementation, we maintained close collaboration and communication with both top-performing teams from previous years and fellow participants this year. We also actively showcased and promoted our project at large-scale exchange events. Through these interactions, we shared experiences and learned from each other's strengths, which helped refine our project. Additionally, we co-hosted popular science events and project exhibitions to drive collective progress. These activities not only improved our project quality but also raised awareness about synthetic biology's crucial role in enabling diverse, personalized, and customized food supply. They also demonstrated how agricultural students contribute to and excel in modern agricultural development.

Timeline for iHP Activities