In 2025, through our project Neurobloom, we explored Integrated Human Practices (IHP) in the field of early intervention for Alzheimer’s disease (AD). IHP was deeply embedded throughout the entire project, creating a mutually reinforcing process.

At the stage of selecting our research direction, global data indicated that dementia incidence is continuously rising. Surveys and interviews with families of patients further revealed the public’s lack of awareness regarding early intervention. Clinicians consistently emphasized that “early intervention is more valuable than late treatment,” which strengthened our determination to focus on early-stage approaches. During the project design phase, discussions with Professor Tang (Yunnan University) and Dr. Song (Xuanwu Hospital) helped us gradually define functional molecules—from the identification of sakuranetin, to optimizing energy metabolism, and further to refining carbon flux allocation and substrate endogenization—leading to a three-stage optimization framework. Inspired by the Welfare Expo, we introduced LPC as a second intervention pathway, thereby expanding the framework into a multi-molecule synergistic intervention strategy. In the safety design stage, visits to nursing homes made us realize that our product must demonstrate solid biosafety. Therefore, we developed a dual kill-switch system (PBAD–T4 and PcspA–T4), and validated through experiments that it could achieve controllable clearance both in vivo and in vitro, triggered by environmental cues. At the stage of application and implementation, interviews with patients’ families and investigations in nursing homes highlighted the real-world challenge of “complex medication processes and heavy burden.” Following Professor Guan’s guidance that “early intervention is more valuable,” we lyophilized our engineered bacteria and encapsulated them into enteric-coated capsules. This ensured stability, compliance, and accessibility, positioning our product as a probiotic supplement for high-risk populations. In the societal engagement stage, we not only took part in charity donations and handicraft activities at nursing homes, recognizing the diverse value of AD interventions, but also visited traditional pharmacies to identify potential natural compounds, exploring the integration of synthetic biology with traditional wisdom. Additionally, leveraging our identity as students, we organized joint science outreach activities between two schools, promoting the concept of “early self-check of symptoms” among peers and advocating prevention over treatment.

Through in-depth engagement with diverse stakeholders, we built a complete feedback loop—from needs identification → functional design → safety optimization → product implementation → social responsibility. This not only demonstrates our commitment to Integrated Human Practices (IHP), but also paves a sustainable pathway for exploring early intervention in Alzheimer’s disease.

Stakeholders

Following the principle of consumer-driven product design, we identified and prioritized key stakeholders essential to Neurobloom’s development. Using Mendelow’s Matrix, we mapped their levels of interest and power, which helped us refine strategies for engagement and co-creation.

Figure: Stakeholders map

• End-users (patients, families at risk of AD): High interest, medium power. They guide our design through surveys and feedback, ensuring accessibility and usability.
• Medical professionals (neurologists, geriatricians, nutritionists): High power, high interest. Their clinical insights validate safety and scientific rationale.
• Institutional partners (hospitals, nursing homes): High power, high interest. They provide testing grounds and adoption pathways for B2B deployment.
• Regulators and policymakers: High power, lower direct interest. Their guidelines shape our compliance and approval path.
• Biotech incubators and CDMOs: Medium power, high interest. They support scale-up, manufacturing, and quality assurance.
• General public and educational communities: Medium interest, lower power. They are key to awareness-building and reducing stigma around early Alzheimer’s interventions.

This mapping allowed us to structure tailored outreach—from professional interviews and pilot collaborations to public education and online engagement—ensuring that every stakeholder’s voice is reflected in Neurobloom’s design and implementation.

Global Perspective

Worldwide, one person is diagnosed with dementia every three seconds, with Alzheimer’s disease (AD) accounting for 60%–70% of all cases. Behind these statistics are countless families facing the loss of memory, language, and even self-identity. The annual societal cost now exceeds one trillion USD, underscoring the urgent need for safer, earlier, and more accessible interventions.

Team Perspective – Needs Assessment

Focusing solely on the disease itself is not enough—what matters equally is whether the public truly understands the value of early intervention, since this directly affects whether patients can receive help during the optimal treatment window.

To address this, we designed and distributed an online survey targeting people of different ages and educational backgrounds, specifically gathering their perceptions of AD progression, symptoms, and early intervention.

From the survey results, we found that:

• Most respondents had some understanding of AD’s basic pathology and symptoms;
• Far fewer respondents truly valued early intervention;
• Many tended to misinterpret AD as merely “normal age-related memory decline,” which often delays timely medical or non-medical intervention.

Needs Assessment: The low awareness of early intervention highlights the urgent necessity of developing low-barrier, highly compliant, and accessible solutions.

Family Members in the Medical Field

At the beginning of our project, we were eager to gain a first-hand clinical perspective on the challenges of Alzheimer’s disease (AD). Compared with relying solely on literature, we needed direct clinical experiences and real patient stories. Since several team members have parents working as doctors, they became our most accessible frontline clinicians—deeply familiar with both public healthcare behaviors and the barriers to early intervention. Thus, we began by interviewing family members in the medical field, using their insights to guide our project toward a more realistic direction.

We organized family discussion sessions, inviting these medical professionals to share their frontline observations. From their personal experiences, they highlighted that AD patients are often diagnosed at later stages, while early symptoms are frequently mistaken by families as “normal aging,” leading to missed opportunities for timely intervention.

From these interviews, we drew three key Insights

1. Value Confirmation – Clinicians unanimously agreed that early intervention is more meaningful and accessible than late-stage treatment;
2. Problem Focus – The public generally lacks awareness of early intervention, which echoes our survey findings;
3. Action Guidance – With the consensus that “early intervention is valuable,” we need to further consult specialists to scientifically select intervention molecules, ensuring our project can be implemented in practice.

Selection of Sakuranetin

After defining early intervention as our project direction, we still faced a key question: Which molecule should we select as the intervention agent? Literature described many candidates, but their safety and efficacy varied significantly.

We consulted Professor Tang from the Department of Neurology at Yunnan University Affiliated Hospital, seeking his clinical experience in drug exploration for AD. He explained that although many candidate drugs are tested each year, very few can achieve both safety and effectiveness. He specifically recommended Sakuranetin and suggested producing it by expressing the F7-OMT enzyme, which converts the substrate Naringenin into Sakuranetin.

A more detailed event record can be found in the attachment:

Insights

1. Direction Established – With Professor Tang’s guidance, we confirmed Sakuranetin biosynthesis as the first functional pathway of our project;
2. Scientific Validation – In the lab, we successfully constructed the engineered strain BL21-OMT;
3. Data Support – BL21-OMT demonstrated the ability to produce Sakuranetin, validating the feasibility of this pathway.

Improving Sakuranetin Yield

Second-Generation Optimization – Yield Enhancement

After completing the first-generation system, we confirmed the production of Sakuranetin, but the yield was still far below the desired level. This led us to consider whether hidden metabolic bottlenecks had been overlooked. To avoid relying solely on trial and error, we sought advice from specialists in Alzheimer’s research.

We discussed our design with Dr. Song from Xuanwu Hospital, who highlighted that Sakuranetin yield depends not only on the expression efficiency of F7-OMT, but also critically on the supply of S-adenosylmethionine (SAM) inside the cell. If SAM levels are insufficient, the conversion efficiency becomes severely limited. He recommended that we address this issue by targeting cellular energy metabolism, specifically by regulating ATP as a key precursor to improve SAM synthesis. Based on this feedback, we recognized the bottleneck in our first-generation system and built the second-generation optimization system.

A more detailed event record can be found in the attachment:

Insights

1. Problem Identification – The yield bottleneck primarily stemmed from insufficient SAM supply, rather than enzyme expression efficiency alone.
2. Optimization Strategy – In the second-generation system, we introduced the ydaO operon from Bacillus subtilis, employing its ATP-sensing riboswitch to dynamically regulate energy metabolism: boosting ATP production when levels are low, and avoiding unnecessary consumption when ATP is abundant.
3. Experimental Outcome – This feedback-regulation mechanism enabled cells to maintain energy homeostasis and enhance SAM availability. Experiments demonstrated that the engineered strain BL21-OMT-YdaO achieved nearly a 90% increase in Sakuranetin yield compared to the first-generation strain.

Third-Generation Optimization – Enhanced Yield Strategy

After achieving nearly a 90% increase in yield with the second-generation optimization system, we encountered a new challenge: energy metabolism optimization alone did not fully resolve the bottleneck of limited carbon flux distribution. To further improve Sakuranetin yield, it became necessary to reassess substrate availability and carbon metabolic pathways.

We discussed this issue with a PhD in biology, who reminded us that beyond regulating energy and SAM levels, a shortage of precursor metabolites could still constrain final product synthesis. He suggested approaching the problem through amino acid metabolism, enhancing the supply of carbon flow and precursors. Inspired by this, we decided to co-express cysE (serine acetyltransferase) to increase the production of cysteine and methionine, thereby indirectly boosting the regeneration cycle of SAM.

A more detailed event record can be found in the attachment:

Insights

1. Bottleneck Identification – Yield limitation stemmed not only from insufficient energy but also from restricted carbon flux and inadequate substrate supply.
2. Optimization Strategy – By co-expressing cysE, we strengthened amino acid precursor synthesis, widened the substrate supply channel, and directed more metabolic flux toward Sakuranetin biosynthesis.
3. Experimental Outcome – The third-generation engineered strain successfully overcame the limitations of the second generation, achieving a further increase in Sakuranetin yield.

Initial Yield Enhancement Design

During our visit to the nursing home “Pleasant Time”, we observed that many Alzheimer’s patients, due to memory decline, often forgot to take their prescribed medicines or supplements on time. This led us to realize that if Sakuranetin synthesis depends on external supplementation of Naringenin, its effectiveness in real-world applications would be unreliable.

A more detailed event record can be found in the attachment:

We consulted Dr. Tian, an expert in the field, who pointed out that relying solely on exogenous substrates creates a major compliance challenge. He proposed a critical solution: to construct an endogenous Naringenin biosynthesis pathway. By introducing a gene module from L-tyrosine to Naringenin (TAL, 4CL, CHS, CHI), engineered bacteria could autonomously produce Naringenin inside the cell, which could then be converted into Sakuranetin by F7-OMT.

A more detailed event record can be found in the attachment:

Insights

1. Problem Identification – Exogenous supplementation of Naringenin poses compliance risks, since patients with memory decline often fail to take it consistently.
2. Solution – Implementing an endogenous Naringenin biosynthesis pathway enables engineered bacteria to stably produce Sakuranetin within the gut, eliminating dependence on additional supplementation.

LPC Production

After completing the design around Sakuranetin, we asked whether other molecules could contribute to early intervention in AD.

At the 2025 China International Welfare & Rehabilitation Expo, we encountered new studies on cognitive impairment in the elderly. A key paper highlighted that gut microbiota alterations are closely linked to AD progression, and that LPC (lysophosphatidylcholine) plays a critical role in modulating the gut–brain axis and alleviating AD pathology. This opened up a new research avenue for us.

If sustained LPC production in vivo is achievable, it could reduce β-amyloid burden, improve synaptic function, and help mitigate cognitive deficits via the gut–brain axis. Based on this, we designed a second functional system: using PLA2 to convert phosphatidylcholine (PC) into LPC.

If sustained LPC production in vivo is achievable, it could reduce β-amyloid burden, improve synaptic function, and help mitigate cognitive deficits via the gut–brain axis. Based on this, we designed a second functional system: using PLA2 to convert phosphatidylcholine (PC) into LPC.

A more detailed event record can be found in the attachment:

Insights

1. New Direction:：LPC was identified as a promising molecule for early AD intervention, forming a second functional route alongside Sakuranetin.
2. Engineering Implementation: We built the LPC-producing strain BL21-PLA2, achieving in vivo PC → LPC conversion.

Safety Kill-Switch System

Throughout development, we kept in mind that safety is central to responsible research and innovation. Regardless of engineering sophistication, if we cannot protect researchers, communities, and the environment, real-world deployment is not viable.

To better understand practical safety concerns, we visited a nursing home. Staff emphasized that “safety must come first.” This feedback led us to implement multi-layered safeguards.

Guided by literature and expert input, we constructed a dual kill-switch system:

• In vivo layer (PBAD–T4 lysis, L-arabinose–induced): When manual clearance is required, patients ingest L-arabinose to trigger lysis for controlled removal.
• Ex vivo/environmental layer (PcspA–T4 lysis, cold-induced): If cells enter low-temperature environments (e.g., accidental release), PcspA activates T4 lysis to prevent spread.

A more detailed event record can be found in the attachment:

Choosing the Product Form

We asked what product format would truly fit into patients’ lives. Function alone is insufficient—if a product is hard to take or hard to store, it won’t deliver value in practice. We therefore engaged families and care facilities to capture frontline needs.

Engagement

Interviews with Families

Families repeatedly stressed concerns not only about “having a drug,” but about complex regimens and heavy cost burdens. This strengthened our resolve to design an accessible, low-barrier health intervention.

A more detailed event record can be found in the attachment:

Academic Guidance

Professor Guan emphasized that “early intervention is more valuable than late-stage treatment.” This guided us to prioritize continuity, swallowability, and ease of use in our product design.

A more detailed event record can be found in the attachment:

Nursing Home Visit

Real-world caregiving revealed that long-term care and complex medication management impose major burdens. Therefore, the product must be simple in form and easy to manage to be viable.

A more detailed event record can be found in the attachment:

Insights

1. Need Confirmation: Users care most about ease of use; simplifying the product format is crucial.
2. Technical Pathway:Lyophilization for stability/shelf-life; enteric capsules to deliver live bacteria to the gut.
3. Positioning: A probiotic supplement for high-risk groups, continuously producing Sakuranetin and LPC, with safety, low cost, and ease of use.

Product Inclusivity

Charity Donations

As our project progressed, we gradually realized that tackling Alzheimer’s disease should not be limited to laboratory breakthroughs alone. True solutions require long-term, collective efforts across society. This prompted us to reflect: beyond scientific innovation, what else can we do to support patients and their families? After team discussions, we decided to actively participate in charity donation initiatives.

A more detailed event record can be found in the attachment:

Insights

1. Deeper Understanding: AD is a long-term battle requiring science, families, and society to work together.
2. Value Extension: Outreach deepened our awareness of social responsibility and real family needs.
3. Action-Oriented: Beyond research, ongoing social actions provide tangible support and raise awareness.

Hands-on Activities with Patients

Beyond pharmacological and nutritional interventions, are there other ways to improve patients’ quality of life? To find out, we organized interactive activities with patients and experienced their daily routines firsthand.

We co-hosted craft sessions with patients, who showed strong engagement and creativity. Caregivers noted that such non-pharmacological interventions can slow disease progression and significantly improve mood and quality of life.

A more detailed event record can be found in the attachment:

Insights

1. Broader View: Interventions are multimodal, not drug-only.
2. Value Affirmed:Non-drug approaches bring emotional relief and QoL gains.
3. Project Insight: Combine probiotic and non-pharmacological approaches for science + empathy.

Multidirectional Scouting (TCM Inspiration)

Beyond Sakuranetin and LPC, could there be other naturally derived molecules that offer new possibilities for the early intervention of Alzheimer’s disease (AD)? With this question in mind, we turned to Traditional Chinese Medicine (TCM) for inspiration.

We visited local traditional medicine shops and spoke with staff and pharmacists to learn about the traditional uses of common herbs for brain health, anti-aging, and memory improvement. For example, Ginkgo, Ginseng, and Acorus were frequently mentioned, as they are widely believed in Chinese folk practice to enhance memory and slow aging. Through these visits, we gathered preliminary experiential knowledge and public perceptions related to these medicinal materials.

A more detailed event record can be found in the attachment:

Insights

1. Idea Expansion: Traditional medicinal herbs provide a potential “candidate library” of natural products, which may contain components valuable for AD intervention.
2. Knowledge Integration: Visiting traditional medicine shops not only helped us understand how the public traditionally addresses “memory decline,” but also reminded us to consider combining modern synthetic biology with traditional wisdom in our project.
3. Next Steps: We will incorporate these candidate natural molecules into future literature research and experimental validation to assess their scientific basis and application potential.

Two-School Joint Outreach

As students, we wondered whether we could leverage our unique identity to spread both scientific awareness and care among our peers. This led us to the idea of organizing joint campus activities, helping young people raise their awareness of AD from an early age.

We organized a joint activity between two schools to promote AD awareness in an interactive and engaging way, with a special focus on the importance of early self-check of symptoms. During the event, we used explanations, quizzes, and Q&A sessions to help peers understand that memory decline is not simply “normal aging,” but can serve as a warning signal. Students also participated in a “Quick Memory Challenge” mini-game, with the top five winners from both schools receiving “Memory Guardian” certificates. In addition, students created handmade photo frames on site, which were later sold in a charity sale, with all proceeds donated to an Alzheimer’s charity organization.

A more detailed event record can be found in the attachment:

Insights

1. Awareness Raised: Through the activity, many participants learned for the first time about the early symptoms of AD and methods of self-check, realizing the importance of prevention over treatment.
2. Social Value: This practice helped us recognize that early detection and intervention not only reduce the burden on patients’ families but also lessen long-term healthcare and caregiving pressures at the societal level.

To-do List

We firmly believe that Neurobloom is not just a competition project, but a sustainable long-term plan. Even after iGEM 2025, we will continue advancing both our research and community engagement, ensuring that our outcomes extend beyond the competition. To build continuity, our school is also preparing to establish an iGEM Academic Research Association, a student-led club dedicated to synthetic biology learning and iGEM preparation. This organization will provide a platform for scientific exploration, team-building, and training, laying the foundation for next year’s competition. Below is the initial draft of our proposed constitution for the association.

Science & Technology

• Multi-molecule synergy validation: Further investigate the combined intervention of Sakuranetin and LPC. → Neuroscientists, Alzheimer’s research groups.
• Metabolic pathway optimization: Use flux analysis and multi-omics to further enhance yield. → Metabolic engineers, synthetic biology professors.
• Animal studies: Validate the effect of engineered bacteria on cognitive improvement in mouse models. → Animal facilities, neuroscience labs, ethics committees.
• Safety evaluation: Test the long-term reliability of the dual kill-switch system in more complex environments. → Biosafety experts, regulatory authorities.

Product & Application

• Formulation optimization: Improve enteric capsule stability and explore formats such as powders and drinks. → Pharmaceutics experts, food engineers.
• Scale-up preparation: Develop small-scale fermentation and lyophilization processes. → Bioprocess engineers, pharmaceutical industry partners.

Society & Outreach

• Public education: Continue early-symptom awareness campaigns for AD. → Nursing homes, patient families, school clubs, NGOs.
• International collaboration: Build partnerships with global academic teams and eldercare institutions. → International exchange platforms, AD research alliances.
• Market research: Assess the real needs of high-risk populations. → Families of patients, caregivers, health management companies.

Future Outlook

Overall, our Human Practices journey reflects our continuous reflection and persistent exploration of how synthetic biology can address the major medical and social challenge of Alzheimer’s disease. Yet our journey will not end here. With the enduring enthusiasm of high school students, we will continue our work beyond the competition: collaborating with neuroscientists and metabolic engineers to optimize Sakuranetin and LPC biosynthesis; working with clinicians and biosafety experts to validate efficacy and safety in animal models and real-world scenarios; partnering with pharmaceutics teams and industry to improve formulations and scale-up production; and consistently engaging with nursing homes, schools, and NGOs to advance public education and care initiatives.

We believe that Neurobloom is not just an iGEM project, but a long-term commitment. It aims not only to provide safer, low-barrier early interventions for patients, but also to ease the burden on families and foster greater societal awareness and support for Alzheimer’s disease. Looking forward, we will continue to pursue innovation at the intersection of science and humanity, contributing our efforts to safeguard both memory and love, as we collectively embrace a brighter future.