Ⅰ. Design
Laying the Responsible Foundation for ProbiEase
The design of ProbiEase was not conceived in isolation but was rigorously shaped by a trilogy of integrated human practices from the very beginning. This phase was dedicated to ensuring our project was both scientifically visionary and deeply responsible.
We started by immersing ourselves in the scientific literature to identify the fundamental gaps in probiotic therapy. We then engaged directly with the public to understand their perceptions and concerns, and most importantly, we listened to the patients who live with Parkinson's Disease every day.
This sequential process---from theoretical understanding, through public perception, to human-centered empathy---provided the critical insights and unwavering conviction that directed our technical work. It ensured that ProbiEase was built on a foundation of real-world need, societal relevance, and a profound respect for the end-users we aim to serve.
1. March-Literature Review
(1) What we did?
We initiated our project with a comprehensive literature review to ground our design in robust scientific evidence. Our investigation revealed a clear consensus on the therapeutic potential of probiotics, as defined by ISAPP. We learned that while clinical evidence is accumulating for conditions like ulcerative colitis and Parkinson's Disease (PD), native probiotic therapies are fundamentally limited by poor colonization and insufficient therapeutic potency.
Critically, our analysis of recent advancements highlighted a paradigm shift: the field is moving from empirical single-strain applications towards rationally engineered consortium-based therapies. We identified that the major hurdle for synthetic consortia is no longer the concept itself, but the lack of standardized modeling and rational design frameworks, leading to fragmented and irreproducible results.
(2) What we gained?
To synthesize our understanding and contribute to the field's foundational knowledge, we systematically reviewed and analyzed existing consortium design strategies. This effort culminated in a comprehensive review article, "Assembly Strategies for Synthetic Probiotic Consortia", which we submitted to the esteemed journal Synthetic Biology and is currently under revision. This process of authoring a review forced us to critically evaluate the entire landscape and solidified our conviction in the need for a principled design approach.
This scholarly work was not passive; it actively shaped our project's core mission. It convinced us that a groundbreaking contribution would be to develop a systematic platform that integrates data-driven selection with synthetic biology to design functional consortia. This foundational insight directly inspired the creation of our AI platform and modeling efforts, setting the stage for a solution that addresses the field's most critical methodological gap.
2. April-The Haitang Festival Survey
(1) What we did?
To ensure our project was not only scientifically sound but also socially responsible and aligned with public perception, we designed and conducted a Knowledge, Attitude, Behavior, and Practice (KABP) survey during the university's Haitang Festival. We distributed the questionnaire on-site and collected 351 valid responses from a diverse demographic, with a concentration of participants aged 18 to 39.
(2) What we gained?
While literature provided the scientific "why," this survey aimed to answer the human-centered "so what?"---specifically, what the public thinks about using engineered nasal probiotics for Parkinson's Disease (PD) treatment. The results provided critical, real-world insights:
(1) Knowledge Gap as an Opportunity: We confirmed a significant public interest in novel drug delivery methods like nasal administration. However, the low awareness of its principles for CNS diseases revealed a crucial communication challenge and an educational opportunity for our project.
(2) Informed Attitudes Shape Design: The positive reception towards the concept after our on-site explanation demonstrated that public acceptance is achievable through clear communication. This finding validated our commitment to transparency and directly influenced our decision to prioritize public education and develop accessible explainer materials alongside our technical work.
This initiative was a foundational Human Practice. The feedback did not just sit in a report; it actively guided our strategy. It convinced us that a responsible project must bridge the gap between cutting-edge science and public understanding. Consequently, we integrated these insights into our core design philosophy, ensuring that from its inception, ProbiEase was being built not just for the world, but with the world in mind.
3. May-Dialogue with Patients in Peking University Sixth Hospital
(1) What we did?
To move beyond textbook knowledge and truly understand the human experience behind Parkinson's Disease (PD), our team conducted in-depth, empathetic interviews with patients at Peking University Sixth Hospital. We listened to their personal stories, daily struggles, and hopes for the future. This was not a mere data collection exercise; it was a conscious effort to center our project design on the people we aim to serve.
(2) What we gained?
The conversations were profoundly illuminating, moving our project's focus from a purely technical challenge to a holistic human one. The insights we gained directly shaped ProbiEase's core objectives:
(1) Confronting the "Invisible" Burden: We learned that the "invisible" symptoms---debilitating insomnia, profound mood swings, and emotional distress---cause immense suffering, often overlooked by others. This insight compelled us to look beyond motor symptoms. It motivated our choice of Glutathione in the therapeutic module, targeting neuroprotection and potential mitigation of oxidative stress-linked non-motor symptoms.
(2) Addressing the Rigidity of Current Treatment: Patients described the strict, unforgiving schedule of medication and the burden of "wearing-off" phenomena. This highlighted the need for a more sustained and manageable therapeutic approach. Our project's vision for engineered probiotics capable of localized, sustained production of therapeutic molecules is a direct response to this need, aiming to provide a more continuous relief and reduce the burden of strict pill schedules.
(3) Understanding the Deepest Hope: The heartfelt plea for a "cure" reinforced our resolve. While our project is a step rather than a final cure, it solidified our mission to pursue a disease-modifying strategy, not just symptomatic relief. This is reflected in our dual-therapy approach, combining immediate symptom management (Levodopa) with long-term protective goals (Glutathione).
This experience was a pivotal moment. It convinced us that tackling PD was not just a significant scientific challenge, but a profound human necessity. Every design decision in ProbiEase---from the choice of disease to the combination of therapeutics---is now imbued with the voices and experiences of the patients we met.
Ⅱ. Build
Guided by Expert and Clinical Insight
The Build phase was defined by our proactive engagement with the clinical frontier. We moved from the foundational insights of the Design phase into active dialogue with leading neurologists and clinicians. Through targeted consultations and participation in high-level academic forums, we continuously refined our engineering strategies. These interactions ensured that every module we built---from therapeutic payloads to safety switches---was not only biologically sound but also clinically relevant and responsibly designed, directly addressing the real-world challenges faced in treating neurodegenerative diseases.
1. May 30-PD Expert Yuan Junliang
(1) What we did?
During the Build phase of our project, we proactively sought to validate and refine our technical approach with clinical experts. We engaged in a dedicated consultation with Dr. Yuan Junliang, Attending Physician from the Department of Neurology at Peking University Sixth Hospital. The session included presentations from Dr. Chen on the "Establishment of Standardized Training Centers" and "Research on Neurodegenerative Diseases," followed by an observational tour of their advanced PD specialty center.
(2) What we gained?
This interaction provided an invaluable, ground-level perspective that directly influenced our engineering priorities and safety considerations.
(1) From 'Cool Feature' to 'Clinical Need': Seeing the center's comprehensive non-pharmacological therapies underscored that effective PD management is multi-faceted. This reinforced our project's core premise: a multi-targeted "cocktail" therapeutic approach is not just innovative but clinically necessary. It validated our decision to combine Levodopa with Glutathione for both symptomatic and potential neuroprotective effects.
(2) Informing Our Safety-by-Design Principle: Learning about the rigorous standards for a specialized PD center heightened our awareness of the clinical safety bar. It made the abstract concept of "biosafety" concrete. We decided to incorporate a robust dual safety module from the outset, ensuring our engineered bacteria are controllable even in a sensitive patient population.
This dialogue ensured that as we moved into the lab to 'build,' our work was continuously guided by the practical realities and stringent requirements of clinical practice.
2. May 17 - The 3rd Neurology Development Forum of Peking University Sixth Hospital
(1) What we did?
To ensure our project remained at the forefront of neurodegenerative disease research, our team attended The 3rd Neurology Development Forum at Peking University Sixth Hospital. We immersed ourselves in presentations from leading clinicians and researchers, covering topics from novel biomarkers and intervention strategies for depression to the latest diagnostic guidelines for cognitive impairments and advances in the treatment of various neurodegenerative diseases.
(2) What we gained?
Participating in this forum provided a high-level, strategic overview of the field's current challenges and future directions, which critically informed our project's development.
(1) Validating the Multi-Target Approach: It reinforced the scientific and clinical rationale behind our decision to engineer a multi-functional consortium capable of addressing multiple pathological pathways simultaneously, rather than pursuing a single therapeutic output.
(2) Identifying Synergies with Emerging Biomarkers: Learning about the latest research on biomarkers (e.g., α-synuclein) and neuroimaging features provided a forward-looking context for our work. It prompted us to consider how future iterations of ProbiEase could not only deliver therapy but also potentially interact with or be monitored through such emerging diagnostic tools, opening avenues for theranostic (therapy + diagnostic) applications.
This experience allowed us to 'build' with a broader perspective, ensuring our engineering efforts are not only technically sound but also aligned with the evolving paradigms of clinical neurology.
Ⅲ. Test
Grounding Innovation in Clinical Insight
The Test phase marked our project's crucial transition from theoretical design to real-world validation.
To ensure our engineered probiotic solution for Parkinson's Disease (PD) was both scientifically sound and clinically relevant, we actively engaged with key end-user stakeholders: frontline clinicians and specialized nurses. Through in-depth consultations with a molecular neuropharmacologist, a PD-specialized neurologist, and an experienced PD nurse, we gained invaluable, ground-level insights that critically shaped our experimental approach and therapeutic strategy.
These dialogues allowed us to pressure-test our assumptions, refine our understanding of PD's complexities, and align our technical build with the nuanced realities of patient care. This phase ensured that ProbiEase is being developed not in isolation, but in continuous conversation with the clinical ecosystem it aims to serve.
1. July 20-Pharmacology Expert Chen Jiangfan
(1) What we did?
During the Test phase of our project, we engaged in a critical consultation with Prof. Chen Jiangfan, a leading expert in molecular neuropharmacology and adenosine receptor biology. We presented our proposed therapeutic approach, including the use of Levodopa and Glutathione as key molecular outputs of our engineered probiotics.
(2) What we gained?
Prof. Chen's feedback provided essential pharmacological and pathological insights that directly influenced our experimental design and therapeutic rationale:
(1) Clarifying Levodopa's Pharmacological Profile: Prof. Chen emphasized the importance of thoroughly understanding Levodopa's pharmacokinetics and stability---especially in the context of local, sustained release within the nasal microenvironment.
(2) Linking Pathology to Therapeutic Output: Drawing from his deep expertise in Parkinson's pathology---particularly the role of α-synuclein aggregation and dopamine depletion---Prof. Chen encouraged us to strengthen the connection between our chosen therapeutics and the underlying disease mechanisms.
These takeaways have been instrumental as we move into the testing of our engineered strains, ensuring that our therapeutic strategy is not only innovative but also grounded in a robust pharmacological and pathological foundation.
2. May 30-Dr. Zhao Danhua
(1) What we did?
During the Test phase, to ensure our project design aligned with real-world clinical practice, we sought direct feedback from frontline clinicians. Our team conducted an in-depth interview with Dr. Zhao Danhua, an Associate Chief Physician specializing in Parkinson's Disease at Peking University Sixth Hospital. We presented our project concept and engaged in a detailed discussion covering early diagnosis, treatment strategies, and future directions in PD management.
(2) What we gained?
This dialogue provided crucial, ground-level validation and refinement points for our project:
(1) Clinical Validation of Our Core Concept: Dr. Zhao's confirmation of the challenges associated with sustained dopamine delivery and her positive outlook on novel drug delivery systems served as strong clinical validation for our project's foundational goal. It reinforced our belief that developing a localized, sustained-release system is a direction worth pursuing.
(2) Emphasis on Holistic Care Integration: Understanding the importance placed on rehabilitation and non-pharmacological therapies in standard care prompted us to consider how our synthetic biology solution could exist within a broader, integrated patient care ecosystem, rather than as a standalone intervention.
This engagement ensured that as we progressed into testing our designs, we were continuously guided by the practical realities and nuanced needs of PD treatment, helping to create a solution that is both innovative and clinically meaningful.
3. May 30-Head Nurse Chen Baoyu
(1) What we did?
During the Test phase, to complement the medical perspective and understand the full spectrum of patient care, we engaged with those at the forefront of daily patient management: clinical nurses. We conducted a focused interview with Head Nurse Chen Baoyu from the Department of Neurology at Peking University Sixth Hospital, who possesses 15 years of specialized experience in PD nursing. Our discussion centered on the "invisible challenges" and practical realities of patient care.
(2) What we gained?
This dialogue provided profound insights that reshaped our understanding of PD's impact and our project's potential role:
(1) Redefining the Problem Space: The conversation starkly highlighted that a successful therapeutic intervention must address the debilitating non-motor symptoms identified by nursing staff, not just the classic motor signs. This expanded our view of what constitutes a "successful outcome" and urged us to consider how our solution might indirectly alleviate or interact with these complex symptom clusters.
(2) The Power of Systematization: Witnessing how standardized, simple protocols could dramatically improve patient safety and reduce caregiver burden inspired us to prioritize ease of use and clear implementation guidelines for our own technology.
Engaging with frontline nursing expertise ensured our project remained grounded in the holistic reality of PD, pushing us to design not just for biological efficacy but for integration into a comprehensive care ecosystem that truly supports patients and caregivers.
Ⅳ. Learn
Integrating Community Insights into Responsible Innovation
The Learn phase represented the final evolution of our integrated human practices, where we engaged with the broader synthetic biology and iGEM community to refine our project's technical and ethical dimensions. Through participation in two major national events -- the CCiC & Synbiopunk conference and the Engineered Living Medicines Symposium hosted by iGEM Peking -- we exposed ProbiEase to critical peer review and interdisciplinary dialogue.
This phase ensured our project evolved through continuous learning, integrating community wisdom to strengthen both scientific rigor and responsible design.
This community-driven learning process directly shaped our final implementation strategy, pushing us to develop more nuanced solutions to the complex challenge of engineering living medicines for Parkinson's disease.
1. August 6~8-CCiC Conference
(1) What we did?
During the Learn phase, we actively participated in The 12th Conference of China iGEMer Community (CCiC) & Synbiopunk 2025. We presented our project through academic poster sessions and delivered a live roadshow presentation, engaging in in-depth discussions with over 100 iGEM teams. These interactions allowed us to showcase ProbiEase's innovative approach to Parkinson's disease treatment while receiving direct feedback from diverse perspectives within the synthetic biology community.
(2) What we gained?
Our participation in CCiC provided multidimensional insights that are shaping the final iteration of our project. The following sessions were particularly impactful:
(1) From the Fireside Chat with Professor Ariel B. Lindner, we gained a global perspective on responsible innovation in synthetic biology. As a founding member of iGEM and a UNESCO expert on biosecurity, Prof. Lindner emphasized that "the real challenge is not just building new systems, but building systems the world is ready for." This inspired us to further strengthen the narrative around the real-world readiness of our safety modules in project communication.
(2) The Biosafety & Responsibility Workshop, led by Dr. Bao Yuhan with presentations from Prof. Xue Yang and Researcher Gao Lu, provided a rigorous framework for evaluating the societal dimensions of our work. It prompted us to systematically document our safety-by-design choices and consider their broader ethical and regulatory context, beyond mere competition requirements.
(3) The panel on "Generative AI and Life Sciences" and the spotlight report "AI-Driven Automated Pipetting" by Roland from Opentrons demonstrated how machine learning and automation are revolutionizing life design and experimental workflows. These sessions convinced us to formally incorporate AI-based predictive modeling and automation strategies into our future development roadmap, particularly for optimizing consortium interactions and improving experimental reproducibility.
Participating in CCiC allowed us to contextualize ProbiEase within the rapidly evolving Chinese synbio ecosystem. The feedback and insights gained are directly informing our final preparations, ensuring that our project is not only competition-ready but also positioned for responsible, real-world impact.
2. August 5-Engineered Living Medicines Symposium
(1) What we did?
On August 5, our team participated in the "Opportunities and Challenges in Engineered Living Medicines" Symposium, hosted by iGEM Peking at Peking University. This gathering brought together 28 iGEM teams from 24 top universities, all focused on developing engineered living therapeutics. We engaged in thematic discussions, and contributed to breakout sessions on targeting, therapeutic logic, and biosafety --- sharing our own approach to controllable probiotic systems for Parkinson's disease.
(2) What we gained?
This symposium provided a unique platform to situate our project within the national landscape of engineered medicine development. The exchanges profoundly shaped our understanding of both technical design and responsible innovation:
(1) Strengthening Therapeutic Logic through Environmental Sensing and Control
Projects like HiZJU-China's tea-inducible system and CUHK-Shenzhen's hypoxia-responsive circuit demonstrated the power of leveraging disease-specific signals to trigger therapeutic action. These examples encouraged us to further optimize our AHL and SppIP-based communication modules to ensure tighter environment-dependent control over Levodopa and Glutathione production.
(2) Advancing from Binary to Tunable Control in Therapeutic Output
A central question posted on the Challenge Wall -- "How can we achieve dose control of therapeutic molecules (e.g., drugs, enzymes), rather than simple ON/OFF output?" -- resonated deeply with our project. This prompted a critical reevaluation of our control module. We are now exploring how to integrate feedback mechanisms or tunable promoters to move beyond all-or-nothing production of Levodopa and Glutathione, aiming for precise, patient-adaptive dosing.
(3) Refining Safety Against Real-World Delivery Risks
We posed the question: "Safety: How to prevent engineered bacteria from escaping into the lungs or ensure their self-destruction, especially with nasal spray delivery?" This sparked extensive discussion about the practical risks of our chosen N2B (Nose-to-Brain) route. The collective insights reinforced the necessity of our dual safety switches, ensuring that our system remains localized and controllable.
(4) Embracing a Human-Centered and Translationally-Minded Approach
The closing remarks by Dr. Zhai Bing from SIAT reinforced that successful engineered medicines must balance technical ambition with clinical relevance and public acceptance. This has motivated us to more clearly articulate the patient-centric rationale of our strategy and strengthen our proactive human practices communication.
This symposium not only provided technical inspiration but also reinforced our conviction that ProbiEase is part of a broader movement to responsibly program biology for treatment. The collective intelligence and shared challenges discussed will continue to inform our final design iterations and presentation framing.
Through this deeply integrated Human Practices journey, we have demonstrated how a synthetic biology project can be thoughtfully shaped by---and meaningfully respond to---the voices of those it aims to serve. By engaging a wide spectrum of stakeholders across the entire DBTL cycle, we have not only strengthened the scientific foundation of ProbiEase but also embedded responsibility and empathy into its core.