Depression is a persistent mental health condition characterized by uncontrollable negative emotions, sleep disruptions, physical ailments, and even suicidal thoughts. Severe depression affects not only the individual but also has wide-reaching consequences on interpersonal relationships and society. According to a 2023 global study by the World Health Organization (WHO), 2.8 million people worldwide are suffering from depression, with the number steadily increasing each year (World Health Organization, 2023).
In everyday life, we frequently experience moments of unhappiness, which psychologists refer to as "negative emotions." These emotions include fear, anger, disgust, sadness, rage, loneliness, melancholy, and annoyance (Positive Psychology, 2019). Persistent negative emotions can increase stress levels, weaken the immune system, and contribute to conditions like anxiety and depression (Seiler A., et al., 2019). Additionally, research on elderly depression patients has shown that reducing negative emotions can significantly alleviate other symptoms of depression, thereby lessening its overall impact (Arslanoglou E., et al., 2019).
Accordingly, recognizing the importance of managing these emotions for overall well-being, we (CCU-Taiwan) chose to tackle the problem of long-term negative emotions, which in turn will relieve depression and its serious consequences. Our project, titled “SERENE,” encapsulates our core concepts through its acronym: S for Self-awareness, E for Emotion Education, R for Revolutionary Probiotic Engineering, E for Enhancement of Serotonin Production, N for Novel Delivery Method (Edible Film), and the final E for Empowering Mental Health.
Our objective is to provide a comprehensive strategy that enables individuals to better understand and manage their emotions, thereby alleviating negative feelings. To refine our approach, we conducted surveys and consulted with psychologists and industry experts. Their valuable insights and feedback have been instrumental in enhancing our strategies, ensuring that we effectively address the emotional health challenges we aim to solve.
▲ Project Concept Diagram
While exploring ways to alleviate negative emotions, we identified another key issue: "Most people seem to lack awareness of their emotions." To address this, we first conducted a survey among over 360 respondents to assess the general public's level of emotional awareness before delving into potential solutions (Figure 1). We hope this approach could allow us to better understand the scope of the problem and tailor our efforts accordingly.
▲ Figure 1: The graph of Emotion Awareness Survey Questionnaire Result
The first two questions revealed that the majority of respondents (>50%) struggle to recognize their emotional states (Figure 1). This is concerning because when people are unable to detect emotional changes promptly, they may delay taking appropriate action. Unresolved negative emotions can gradually build up, increasing the likelihood of mental health issues such as depression. This underlines the critical role of emotional self-awareness and management in maintaining psychological well-being. Thus, enhancing the public’s ability to recognize and manage emotions should be a key focus in future mental health education efforts.
The next three questions showed that more than half of the respondents are unable to self-analyze the causes of their emotions or connect them to physiological responses. They also struggle to recognize how their expressions and body language communicate their emotions. These findings suggest that people often overlook emotional cues reflected in their behavior, which are tied to their physiological state. Overall, the survey supports our observation that many individuals lack a deep understanding of their emotions.
From our survey, it's clear that "Most people tend to have limited awareness of their emotions," particularly in areas related to analyzing and recognizing them. To further verify these findings and examine the impact of negative emotions on individuals, we consulted with clinical psychologist Min-Xiang Zhang, who has extensive experience in the field, and also an expert in emotional awareness and mental health.
▲ Clinical psychologist, Mr. Min-Xiang Zhang
According to his clinical experience, he agrees that “Many people frequently lack a clear understanding or awareness of their emotional states.” And he thinks that the main reason for the lack of emotional awareness is lack of understanding of themselves and their emotions.
At the same time, he also put forward the connection between negative emotions and stress. He mentioned that long-term negative emotions will lead to stress. Then, the stress caused by long-term negative emotions can affect physical health, and lead to issues such as headaches, insomnia, neck and shoulder pain, and autonomic nervous system disorders. Additionally, they may even contribute to the onset of depression.
Based on our background investigations, we believe that achieving the goal of "alleviating negative emotions among the public" must start by raising awareness of one's emotional state. By enhancing self-awareness, individuals can better utilize simple and effective methods for managing negative emotions, thereby optimizing the overall impact of these interventions. Raising emotional awareness is a crucial first step toward fostering emotional resilience and promoting mental well-being.
▲ Interview with clinical psychologist Min-Xiang Zhang
To help individuals globally become more aware of and understand their emotional states, we developed a health management app called "Pokefish." The app aims to provide users practical tools and insights to monitor and manage their emotions, promoting emotional well-being through accessible, user-friendly features.
▲ The app's homepage
Pokefish offers two core features designed to support emotional well-being:
Stress Measurement:
Using the Finger Photoplethysmography (FPG) technique, Pokefish measures Heart Rate Variability (HRV) to generate a stress index. By simply placing a finger over the phone’s camera, the app can assess the user's stress levels within seconds, providing real-time insights into their emotional state.
Tips to Alleviate Negative Emotions:
Pokefish provides a range of resources to help users reduce stress, including work and rest planning, breathing exercises, and yoga. When stress levels rise too high, the app offers real-time suggestions for stress relief to help users regain balance.
To increase user engagement, Pokefish is gamified as a therapeutic mini-game, encouraging daily check-ins for consistent use. Additionally, the app is integrated with our flagship product, allowing users to collect points by scanning a QR code on beverage seals. This rewards system enhances user loyalty and makes mental health management more interactive and fun.
Through promotion at various events and on social media, we aim to expand Pokefish's reach, enabling more people to monitor and understand their emotions quickly and easily. With its simple stress-measurement process, users can manage their emotional health anytime, anywhere, making it a practical tool for everyday use. This emphasizes the convenience and practicality of the app while highlighting the importance of user engagement and promoting emotional self-awareness. (App details available here).
To enhance emotional awareness practically and in the short term, we invited clinical psychologist Min-Xiang Zhang, who had previously collaborated with us, to lead a seminar titled "How to Identify Your Emotions." The event was well-attended and highly engaging. According to pre- and post-seminar evaluations, participants showed a remarkable improvement in their emotional awareness. On average, there was a 60% increase in their ability to recognize and understand their emotions compared to before the seminar. This substantial increase underscores the effectiveness of targeted educational initiatives in promoting emotional intelligence and self-awareness among attendees. This substantial improvement highlights the effectiveness of such educational efforts in fostering emotional intelligence and self-awareness among participants. Such results highlight the value of psychological education in fostering better emotional management skills within a relatively short time frame.
(Seminar details available here)
▲ On-site emotional awareness seminar
After helping people enhance their emotional awareness, we began exploring whether we could develop a solution that is not only accessible, effective, and practical but also seamlessly integrated into daily life. Our goal was to assist people in alleviating negative emotions through a synthetic biology-based approach.
Probiotics emerged as an ideal platform for this, offering a natural, easy-to-consume supplement with the potential for direct benefits to users. Through research, we identified serotonin—the "happy hormone"—as a promising target for mood regulation. By engineering probiotics to synthesize serotonin or mood-enhancing compounds, we could develop an innovative, biology-based solution to promote emotional well-being.
This approach connects cutting-edge synthetic biology with everyday health practices, offering a practical and scientifically grounded method for improving mental health.
Consulting with Synbio company
To verify the market potential of 5-HTP-producing probiotics, we interviewed Ruiren Zhang, CEO of Trade Wind Biotech, a leading probiotics company in Taiwan. He highlighted that the global probiotics market is approximately USD 7.5 billion. Zhang also emphasized the critical benefits of probiotics, including their ability to regulate intestinal flora, stabilize coexisting bacterial ecosystems, address unknown health issues, and significantly improve overall physical health. Based on his insights and recommendations, we focused on probiotics as the central element in our synthetic biology approach. This decision was influenced by both the market opportunity and the health advantages of probiotics.
▲ CEO of Trade Wind Biotech, Mr. Rui-Ren Zhang
▲ Interview Mr. Rui-Ren Zhang, CEO of Trade Wind Biotech
Consulting with the primary investigator
After selecting serotonin as our primary target, we consulted with our primary investigator, Dr. Weng. Dr. Weng pointed out an essential problem that serotonin could not pass the blood-brain barrier to function in the brain. However, the serotonin precursor, 5-HTP, can pass the blood-brain barrier. We then focused on the synthesis of 5-HTP in probiotics. After extensively reviewing the related references and the projects raised by previous iGEM teams, we learned that Tryptophan hydroxylase 1 (TPH1) is the primary enzyme producing 5-HTP from tryptophan. However, we also found several issues related to 5-HTP production in probiotics, which led us to refine the 5-HTP synthesis system:
Refinement 1: Engineering TPH1 into a monomer
The previous report indicated that human TPH1 (hTPH1) forms oligomers in the cytosol, which causes aggregation while expressed in probiotics. Accordingly, we introduced a biobrick for monomeric hTPH1, which deletes the 99 a.a. at the N-terminal and 24 a.a. at the C-terminal, for iGEM (Wang et al., 2018)
Refinement 2: Establishing BH4 coenzyme system
The biogenesis of 5-HTP depends on BH4 coenzyme recycling, which is mediated by two enzymes, PCBD1 and QDPR (Wang et al., 2018). Accordingly, we introduced these two new enzymes into an iGEM biobrick. To our knowledge, the BH4 coenzyme system is only found in E. Coli. Therefore, we selected Nissle 1917 (EcN) as our probiotic carrier.
Refinement 3: Promoting and regulating 5-HTP production
Our kinetic modeling indicated that 5-HTP production could be significantly improved by clustering all three enzymes. Accordingly, we applied rolling circle replication to produce DNA scaffolds and fused all three enzymes with zinc finger binding domains that recognize the DNA scaffolds. Finally, we applied a protocatechuic acid (PCA)--regulated promoter to control the DNA scaffold and 5-HTP synthesis (Bulyk et al. 2001; Conrado et al. 2012).
Moving forward, while probiotic powders are commonly packaged in sealed strip forms, we sought to innovate by transforming the application of mood-enhancing probiotics into a more engaging and widely accepted form. We came up with the idea of integrating mood-promoting probiotics with a daily beverage to make the supplement more appealing and accessible.
Inspired by the keywords "convenient" and "daily life," we recognized that customized beverages are a staple in Taiwanese culture. According to a survey, Taiwanese individuals consume up to 6.7 cups of customized beverages per week (Health Promotion Administration, 2018). This popular habit presents an ideal opportunity to deliver synthetic biology products in a simple, convenient way. In Taiwan, customized beverages are typically sealed with film to preserve freshness—a perfect medium for innovation.
▲ Drinking customized beverages is a widely embraced and ingrained habit among Taiwanese people
Building on this, we decided to integrate our mood-enhancing probiotics directly into sealing films for these drinks, allowing consumers to benefit from probiotics while enjoying their daily drinks. This innovative approach connects the cultural beverage trend with scientific advancement, offering an accessible solution for promoting emotional well-being.
We encapsulate mood-enhancing probiotics within an edible, water-soluble film placed beneath the sealing film. As the consumer drinks the beverage, the encapsulating film dissolves, gradually releasing the probiotics into the drink. This innovative approach transforms the act of enjoying customized beverages into an opportunity to effortlessly consume probiotics, thereby promoting emotional well-being in a fun, convenient, and seamless manner.
To achieve this, we extensively researched various edible materials that could be used for the encapsulating film. We identified sodium caseinate as a promising option due to its excellent solubility and compatibility with the beverage. Sodium caseinate films dissolve quickly and efficiently, ensuring that the probiotics are released into the customized beverages without altering their taste, texture, or appearance. This means that consumers can enjoy their customized beverages without noticing any difference, all while reaping the added health benefits of probiotics.
By integrating probiotics into the sealing films of customized beverages, we aim to create a novel experience that merges health benefits with the enjoyment of a beloved cultural staple. This innovation makes it easier for consumers to incorporate probiotics into their daily routine and enhances the appeal of customized beverages by adding a functional health component.
Interview with sealing machine manufacturers
As we pursued the idea of incorporating probiotics into customized beverages via edible sealing films, we consulted with sealing machine manufacturers to gather technical insights. While they found the concept innovative and promising, they highlighted several hygiene-related concerns. Specifically, they cautioned that encapsulating probiotics beneath the sealing film could introduce contamination risks and foster bacterial growth, particularly in Taiwan's warm and humid climate. Ensuring the safety and cleanliness of the probiotic-infused film could therefore pose a significant challenge in maintaining product hygiene and consumer safety.
▲ Visiting a tea shop and operating a sealing machine
Interview with beverage practitioners
During our discussions with various beverage store owners, one common theme emerged: the ability to quickly and conveniently deliver happiness to customers is key. Many store owners believe that integrating mood-enhancing probiotics into beverages would enhance customer satisfaction and drive repeat purchases. However, they emphasized that the success of such an innovation would depend on ensuring both safety and convenience. If these concerns can be addressed, most stores expressed strong interest in adopting this approach, viewing it as an opportunity to improve customer service and differentiate their business models.
▲ Interview with beverage practitioners
After developing our synthetic biology approach to alleviate negative emotions, we aimed to offer a more comprehensive solution. To that end, we consulted clinical psychologist Min-Xiang Zhang again, who emphasized that strategies for alleviating negative emotions can be categorized into two main areas: "psychological" and "physical".
On the psychological side, seeking help from a professional psychologist or engaging in positive social interactions can effectively reduce negative emotions by providing emotional support and cognitive coping mechanisms. For the physical aspect, moderate exercise and enhancing physical connections with others are also viable methods. Physical activities like exercise can trigger endorphin production, often referred to as the body's "feel-good" chemicals, which naturally uplift mood and alleviate stress. Strengthening interpersonal physical connections, such as through team sports or group activities, can similarly help mitigate feelings of isolation and promote well-being. By addressing both psychological and physical factors, we aim to provide a well-rounded solution for managing negative emotions.
First, for the psychological aspect, to foster positive social interactions, we began by focusing on the local community. We organized a "Free Hug" event at various locations across Taiwan, including the Wenhua Road Night Market, one of the famous night markets in Chiayi, Taiwan. We invited both children and adults to participate. To increase engagement, we incorporated a lucky draw to attract more people. During the event, participants were given stickers to express their mood, and the majority reported feeling happy—a clear indicator of positive emotions being fostered.
This initiative demonstrated how simple, spontaneous social interactions could uplift people’s spirits. By organizing a local event that encouraged connection and warmth, we aimed to show the psychological benefits of positive social engagement in a practical way.
▲ Free Hug Event at Wenhua Road Night Market
On the physical side, we chose to engage with the local community, particularly focusing on the elderly, as Chiayi County, where our university is located, has the highest aging population in Taiwan. We organized a physical exercise activity specifically designed to uplift the mood of the elderly and help alleviate their negative emotions.
To ensure the effectiveness of the event, we collaborated with Mr. Cang-Hua Wu, a professional physical therapist with extensive experience in elderly care, to lead the “Elderly Mental Health Promotion and Recreational Activities.” His expertise provided a safe and engaging environment for the participants.
After the activity, we gathered feedback from the elderly participants, asking them about their feelings and current mood. All of them reported feeling happier and more relaxed, highlighting the positive impact of physical exercise on emotional well-being. This event successfully demonstrated the benefits of physical activity in promoting emotional health among the elderly.
▲ Physical therapist, Mr. Chang-Hua Wu
▲ Elderly Mental Health Promotion and Recreational Activities
To effectively and comprehensively communicate our project and mission, we adopted two core strategies for promotion: Education and Collaboration. Both strategies help maximize the reach and impact of our project.
Education aims to raise awareness and deepen understanding of our key topic, focusing on both local and global audiences. We've implemented various online and offline initiatives to engage people, such as Social Media Platforms, Open Lab Events, and Campus Campaigns (click each for detailed information). These activities help bridge the gap between our research and the public, ensuring our message resonates with a wide audience.
Collaboration emphasizes building partnerships with other teams and individuals. By sharing knowledge and ideas, we continuously improve through collective feedback. Our initiatives include the Taiwan iGEM Meetup, Online Meetings with other iGEM teams, and creative actions like Postcards and Cup Sleeves (click each for detailed information). These collaborations enrich our project and foster a strong network of like-minded individuals.
After achieving preliminary results, we sought to assess the product's market potential by evaluating the acceptance and opinions of beverage shop brands regarding our mood-enhancing probiotic product. This feedback is essential for understanding its marketability. To gather insights, we reached out to dozens of beverage shop operators and conducted a survey. By visiting and sharing our ideas, many shops expressed interest and provided encouragement. About 50% of the operators showed interest in the product (Figure 2). They noted that the concept was unlike anything they had seen before, sparking curiosity and optimism for its market potential.
Moreover, over 60% of the beverage shops believed that our product would positively impact beverage sales (Figure 3). The operators felt that this mood-enhancing probiotic product could not only diversify their offerings but also attract more customers, particularly those eager to try innovative and health-focused beverages. The feedback suggests that this product has strong market competitiveness, as operators see it as a potential draw for customers seeking new and unique experiences.
▲ Visiting the beverage shops' operators
▲ Figure 2: The beverage shops' interest in our project
▲ Figure 3: The potential market impact of our product
Simultaneously, we conducted an online survey, receiving responses from approximately 300 participants. The majority of respondents were under 30 years old (Figure 4), which aligns with the observation that younger generations dominate online spaces. The second chart highlights that a substantial number of Taiwanese people frequently consume beverages (Figure 5), while the third chart reveals significant interest in our product among younger demographics (Figure 6). These findings suggest that our mood-enhancing probiotics could primarily target the younger generation, with potential to expand to a wider consumer base as the product gains traction.
▲ Figure 4: The age distribution of respondents
▲ Figure 5: The frequency of consuming beverages of respondents
▲ Figure 6: The public's interest about our project
The sealing film manufacturers provided valuable insights on broadening the application of sodium caseinate films beyond sealing films. They suggested that these films could also be applied to other products within the bubble tea industry, such as paper straws or individually packaged tea bags. By doing so, the films would not only deliver probiotics in a controlled and hygienic manner but also minimize challenges related to shelf-life and storage.
For instance, embedding probiotics in paper straws would release the probiotics as the consumer sips the beverage, offering a similar benefit while potentially reducing exposure to external contaminants. Likewise, using sodium caseinate films in individually packaged tea bags could introduce probiotics into various drinks, extending the benefits of our innovation beyond bubble tea and into other beverages.
By expanding the use of sodium caseinate films in this way, we aim to create a versatile solution that enhances consumer health while maintaining strict hygiene standards. This approach addresses the concerns raised by manufacturers and opens up new opportunities for incorporating probiotics into everyday products, thereby promoting well-being in a broader context.
To effectively implement the principles of “Integrated Human Practices,” we focused on addressing the risks associated with depression and promoting emotional well-being through a comprehensive, multi-faceted approach.
Recognizing the prevalence of unhappiness and depression, which often stems from prolonged negative emotions, we conducted interviews with psychologists. These discussions highlighted a common struggle among individuals to identify their own emotions, which can intensify emotional distress.
To tackle this issue, we adopted a two-pronged strategy: awareness improvement and convenient solutions. The "Awareness Improvement" included developing tools such as the Pokefish App and hosting an Emotion Awareness Seminar to aid individuals in better understanding and managing their emotions, while the "Convenient Solution" includes the introduction of the SERENE Beverage and other events designed to alleviate people's mood.
Throughout this process, we observed positive outcomes from our initiatives. Our promotional efforts through education and outreach garnered positive feedback from both the public and industry stakeholders. Additionally, we maintain a forward-looking perspective, focusing on future developments in our approach. In summary, our comprehensive strategy aims to alleviate negative emotions and foster emotional well-being through practical solutions and awareness initiatives, ultimately enhancing the mental health landscape for our community.
▲ Full name of SERENE