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Human Practices

Yiming Zhang, the founder of TikTok, once stated that your ability to receive information determines your production and output. We believe the same applies to the iGEM project. The core of our Human Practices work is to transmit, acquire, and iterate information timely and comprehensively.

Background

Inspiration

Our story with rhinosinusitis started from personal experience. Some of our close relatives and friends suffer from this disease and its devastating impacts. In fact, this is not a rare phenomenon. On social platforms, we collected numerous help-seeking posts from chronic rhinosinusitis patients, who detailed their discomfort and exchanged symptom relief tips in their posts. However, the abundance of pleas contrasts sharply with the scarcity of professional advice—none of the posts received replies mentioning any drug capable of curing this disease. Consequently, patients endure significant suffering without access to viable treatment options. Moreover, on social media platforms, which are typically saturated with information, there is a striking scarcity of content related to chronic rhinosinusitis—be it news updates, or general discussions. Given the severity and societal impact of this disease, it appears it has not received the attention it deserves. We have long hoped to change this situation but we lack inspiration and don’t know where to start.

To our delight, two papers published in Nature earlier this year provided a breakthrough. They revealed GZMK as a promising biomarker and therapeutic target for chronic rhinosinusitis.[1]

Based on this, we are considering whether it is possible to develop a diagnostic and therapeutic strategy for chronic rhinosinusitis.

Integrity Identification

In the initial stages of our project topic selection, we conducted a comprehensive duplication check to ensure proper acknowledgment of all individuals and organizations potentially related to our project. Our research mainly focused on important topics such as rhinosinusitis treatment strategies, protein de novo design algorithms, and protein binder development. Through systematic literature reviews, analysis of statistical data from official sources, and evaluation of industry trends via corporate disclosures, we studied prior achievements made by iGEM teams, enterprises, and research institutions, etc. The results confirmed our project’s novelty with almost no overlapping initiatives. All referenced contributions have been appropriately credited. We hereby reiterate our gratitude to every individual and team that supported our work.

In-depth Investigation

To better answer these questions, we intend to conduct in-depth research to further understand chronic rhinosinusitis. This investigation is expected to enhance our comprehension of the impact of chronic rhinosinusitis and the current status of its diagnosis and treatment, thereby helping us define the value of our project. Our research will primarily involve literature reviews using the PubMed database, industry analysis, and participation in interviews with both patients and medical practitioners in this field.

Prevalence of chronic rhinosinusitis

According to our research, chronic rhinosinusitis has an estimated prevalence of 8% in China, meaning that approximately 107 million individuals have CRS. Expanding our vision to the international landscape, chronic rhinosinusitis is also highly prevalent worldwide, with an estimated prevalence of 10.9% in Europe, 16% in the United States, and 6.95% in Korea.[2]

Symptoms and negative impact of chronic rhinosinusitis

Chronic rhinosinusitis is characterized by persistent inflammation of the nasal mucosa and paranasal sinuses that lasts for at least 12 weeks, typically accompanied by the formation of nasal polyps within the nasal cavity. Patients are often burdened by a range of symptoms such as persistent nasal congestion, loss of smell, rhinorrhea, facial pressure or pain, and postnasal drip.[3]

In clinical practice, the most prominent symptoms of rhinosinusitis typically include initial rhinitis, thick yellow-green nasal discharge, headache, and symptoms persisting for over ten days.

As a result, patients often endure a state where their condition, while not life-threatening, is debilitating and severely compromises their quality of life, posing physical and psychological burden on patients. [2]

Also, chronic rhinosinusitis represents a global health burden with significant epidemiological impact. The disease burden includes frequent clinical visits, productivity loss, and socioeconomic costs. A study targeting 49 adult patients receiving Omalizumab treatment revealed that 46.9% of the participants reported personal costs of €11-€50 per hospital visit, with some incurring over €1,300 annually.[4]

Existing diagnosis approaches for chronic rhinosinusitis and their limitations

Currently, doctors determine the disease based on the patient's symptoms first and then confirm rhinosinusitis via objective indicators. They first perform an initial check by simply opening the nasal passage to observe for pus or swelling. If the situation is unclear, they then rely on nasal endoscopy for a clearer examination. For suspected but non-typical cases, a CT scan is considered for confirmation, as it clearly reveals inflammation inside the sinuses.

Through conversations with patients, we have summarized the current diagnostic landscape for chronic rhinosinusitis and their attitudes towards it.

  1. Only clear nasal discharge and nasal obstruction are observed in the early stage of the disease, which makes it hard to distinguish it from a common cold or rhinitis. As a result, patients with rhinosinusitis often seek medical attention only when they experience noticeable physical discomfort. By this stage, the disease has typically progressed to the middle or advanced stages. This delay causes patients‘ unnecessary suffering and damage that could have been avoided, while also making treatment much more complicated.
  2. Although detection technology like CT scan continues to advance, they generally have low acceptance among patients. More seriously, CT is ineffective for detecting silent lesions, such as those in the sphenoid sinus, which lack obvious nasal secretions. As for nasal endoscopy, it involves distressing mucosal injury, and results are relatively unreliable.
  3. The overall diagnostic process is often cumbersome, involving multiple follow-up visits and trips to different specialist clinics. This is a issue notably highlighted by the patients we interviewed.

Existing treatment approaches for chronic rhinosinusitis and their limitations

Multiple treatment options exist for chronic rhinosinusitis, including corticosteroid therapy, saline irrigation, functional endoscopic sinus surgery, as well as monoclonal antibody biologics such as Dupilumab, Omalizumab, Mepolizumab etc. In clinical practice, a cross-sectional survey of 78 ARS members revealed that off-label nasal steroid irrigations and dupilumab are the most commonly used when treating chronic rhinosinusitis with nasal polyps.[2]

According to our interview with Dr. Li, the primary goal in treating eosinophilic rhinosinusitis is to control inflammation to reduce recurrence. To achieve this, physicians first prescribe corticosteroid nasal sprays such as mometasone furoate, fluticasone propionate, or budesonide. For patients with severe symptoms, in addition to topical steroids, saline nasal irrigation and biologic therapies like dupilumab and omalizumab are used. In particularly severe cases, surgical intervention may be necessary, including sinus incision for pus drainage and correction of sinus anatomy to improve ventilation.

Based on our research findings and interviews, we have compiled a list summarizing current common treatment approaches for chronic rhinosinusitis. Despite their prevalence, these therapeutic strategies have many disadvantages that can be improved.

Brief Introduction Defects
Corticosteroids It is a first-line therapy for ECRS, reducing nasal mucosal inflammation and decreasing nasal polyp size. Its therapeutic efficiency has been clinically proven and it is used globally. 1. Potential side effects: Long-term topical use in nasal cavity may lead to nasal mucosal atrophy and bleeding. Systemic use carries risks of bone density loss and compromised immune function.
2. Possibility of recurrence.
saline irrigation It effectively clears secretions and reduces inflammatory mediators. Its beneficial effects on postoperative recovery has been confirmed. As an adjunctive therapy, it cannot achieve a cure for rhinosinusitis.
endoscopic sinus surgery It removes nasal polyps and restores sinus ventilation. High postoperative recurrence rate
biologics These drugs are developed based on understanding disease pathogenesis, offering certain precision advantages. 1. It requires prolonged development timelines and substantial research investment, therefore it is relatively expensive.
2. Its potential side effects include conjunctival inflammation and headaches.
Traditional Chinese Medicine Chinese acupuncture emerged as the strategy consistently perceived to be both the most effective and minimally adverse. Post-treatment observations showed resolution of nasal obstruction and epistaxis, accompanied by marked mitigation of sinusitis manifestations. However, it still needs further investigation to determine whether this approach is actually effective.

In addition, through targeted research and interviews, we have gathered the latest authoritative guidelines from diverse sources. This has enabled us to build a comprehensive, globally-informed understanding of current chronic rhinosinusitis diagnosis and treatment methods.

Through in-depth background research, we have found that chronic rhinosinusitis indeed imposes enormous health and economic burdens on individuals, families, communities, and society as a whole. However, current diagnostic methods often lack timeliness, and treatment strategies are not sufficiently precise—both presenting significant limitations. This reinforces the scientific problem our project aims to address: we intend to fully leverage the dual role of GZMK as an early diagnostic marker and a promising therapeutic target for chronic rhinosinusitis, in order to achieve early detection and precise treatment of the disease.

Our aspiration extends far beyond simply developing a test strip or medication. More importantly, we hope our efforts can bring small but meaningful changes to patients' lives. Also, we hope our efforts can serve as a bridge of understanding between the public and patients. We hope more people will learn about and prevent this disease, and we also hope that the suffering of rhinosinusitis patients will finally "be understood."

Reference

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[1] Lan F, Li J, Miao W, Sun F, Duan S, Song Y, Yao J, Wang X, Wang C, Liu X, Wang J, Zhang L, Qi H. GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases. Nature. 2025 Feb;638(8050):490-498. doi: 10.1038/s41586-024-08395-9. Epub 2025 Jan 15. Erratum in: Nature. 2025 Feb;638(8052):E45. doi: 10.1038/s41586-025-08712-w. PMID: 39814882; PMCID: PMC11821540.

[2] Liu Z, Chen J, Cheng L, Li H, Liu S, Lou H, Shi J, Sun Y, Wang D, Wang C, Wang X, Wei Y, Wen W, Yang P, Yang Q, Zhang G, Zhang Y, Zhao C, Zhu D, Zhu L, Chen F, Dong Y, Fu Q, Li J, Li Y, Liu C, Liu F, Lu M, Meng Y, Sha J, She W, Shi L, Wang K, Xue J, Yang L, Yin M, Zhang L, Zheng M, Zhou B, Zhang L. Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis. Allergy Asthma Immunol Res. 2020 Mar;12(2):176-237. doi: 10.4168/aair.2020.12.2.176. PMID: 32009319; PMCID: PMC6997287.

[3] https://synapse.patsnap.com/article/what-are-the-key-players-in-the-chronic-rhinosinusitis-with-nasal-polyps-treatment-market

[4] Dungan L, Little F, O'Connor N, Cox F. The patient perspective on use of Omalizumab in the in-hospital setting. Ir J Med Sci. 2025 Jun;194(3):793-795. doi: 10.1007/s11845-025-03978-5. Epub 2025 Jun 25. PMID: 40560316; PMCID: PMC12276100.

[5] Subspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Subspecialty Group of Rhinology, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of chronic rhinosinusitis (2018)]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Feb 7;54(2):81-100. Chinese. doi: 10.3760/cma.j.issn.1673-0860.2019.02.001. PMID: 30776860.

[6] Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600. PMID: 32077450.

[7] Payne SC, McKenna M, Buckley J, Colandrea M, Chow A, Detwiller K, Donaldson A, Dubin M, Finestone S, Filip P, Khalid A, Peters AT, Rosenfeld R, Akrami Z, Dhepyasuwan N. Clinical Practice Guideline: Adult Sinusitis Update. Otolaryngol Head Neck Surg. 2025 Aug;173 Suppl 1:S1-S56. doi: 10.1002/ohn.1344. PMID: 40742114.

Project Discussion

Wetlab Discussion: How to Obtain Better GZMK-binding Proteins and Small Molecule Inhibitors

July 1st 2025

coffee
Dr. Tao Wu

After deciding to use de novo designed GZMK-binding proteins as the capture receptors for our detection kit, we engaged in discussions with Dr. Tao Wu and Dr. Zhizhi Wang to ensure the protein design models we employed were appropriate, reliable, and exhibited sufficiently high performance.
Dr. Tao Wu possesses deep expertise in different models and design principles of de novo protein design. To explore optimal protein design strategies, we held in-depth discussions with Dr. Wu covering aspects such as sequence selection criteria for binding proteins, hotspot selection methods, and affinity enhancement strategies.

Discussion Points:

1. Optimization of Technical Pathway - Incorporating "Affinity" as a Key Metric and Implementing Protein Docking
The team initially planned to screen candidate sequences relying solely on AlphaFold predictions and scoring. Dr. Wu recommended adding "affinity" as a crucial screening metric alongside this. He also suggested performing an additional step of protein docking to filter for sequences demonstrating better complementarity. Regarding the choice of affinity prediction models, Dr. Wu indicated he could recommend models known to perform effectively.

2. Hotspot Selection - Prioritizing Binding Sites from Natural GZMK-Binding Proteins
Regarding hotspot design, Dr. Wu advised us to start from the known binding sites of natural GZMK-binding proteins or antibodies. He also suggested utilizing antigenic epitope prediction models to aid in hotspot screening.

3. Affinity Optimization - Combining In Silico Mutagenesis with Scoring for Iterative Improvement
For affinity optimization, Dr. Wu recommended iteratively enhancing the affinity of candidate sequences by constructing in silico mutations at specific sites (within a window of approximately 10 amino acids) and screening them based on their scores.

Dr. Wu also referred us to a helpful article on designing binders for membrane proteins titled Mapping targetable sites on the human surfaceome for the design of novel binders.

July 4th 2025

coffee
Dr. Zhizhi Wang

To confirm the feasibility of our experimental design and gather broader advice on binding protein design, we subsequently spoke with Dr. Zhizhi Wang two days later. Dr. Wang, a former postdoctoral trainee of Professor David Baker, focuses on de novo protein design to address clinical needs, such as in neurodegenerative diseases.

Dr. Zhizhi Wang, former postdoc trainee of Professor David Baker (2024 Nobel prize of Chemistry), his research focuses on de novo protein design to address clinical needs like neurodegenerative diseases.

Discussion Points:

1. Project Direction – Engaging with Clinicians to Ensure Relevance to Clinical Needs
Dr. Wang affirmed the soundness of our experimental design. He additionally recommended that, beyond literature review, we directly communicate with clinicians to gain deeper insights into current real-world rhinosinusitis diagnosis and treatment protocols, as well as the challenges faced in clinical practice.

2. Optimization of Technical Pathway – Leveraging Natural GZMK-Binding Proteins as a Starting Point
After understanding the challenges we encountered with our initial de novo design approach and Dr. Wu's suggestions, Dr. Wang indicated that the low success rate might stem from the structural characteristics of GZMK itself. He suggested that starting from existing natural GZMK-binding proteins might yield a higher success rate. This recommendation aligned closely with the advice from Dr. Tao Wu.

Hardware Discussion: Suitable Methods for High-Throughput Expression and Affinity Measurement

July 1st, 2025

coffee
Professor Yifan Liu

To identify binding proteins with high affinity for GZMK, the team initially proposed using microfluidic-based high-throughput expression methods combined with affinity detection. This system would not only enable rapid expression of top-scoring de novo designed binding proteins but also directly measure their binding affinity. To explore the feasibility of implementing high-throughput protein affinity screening on a microfluidic chip, we held discussions with Professor Yifan Liu, who specializes in high-throughput screening and detection technologies, as well as high-throughput microfluidic development.

Discussion Points:

1. How to balance high throughput, low consumption, and platform innovation?
Traditional continuous-flow microfluidic chips, while capable of manipulating small volumes, rely on continuous fluid input and output. This operating mode leads to significant buffer wastage during prolonged incubation or measurement processes.
After understanding our objectives, Professor Liu introduced us to an innovative technology recently developed in their lab — droplet microfluidics. By encapsulating reaction systems in isolated, picoliter-to-nanoliter droplets, each droplet becomes a miniature "biochemical reactor." This elegantly resolves the wastage issue, enabling truly "static" ultra-small volume reactions while retaining the high-throughput and parallelization advantages of microfluidic technology. It represents a solution that balances efficiency, economy, and technical innovation.

2. Methods for detecting binding protein affinity
Given the limited project timeline, Professor Liu recommended that our microfluidic system adopt a dual-inlet chamber design. The fluorescence detection component is relatively complex and needs to be designed based on the specific implementation of FCS (Fluorescence Correlation Spectroscopy) and qFRET (quantitative Förster Resonance Energy Transfer). We presented literature data modeling methods that use FCS to determine protein affinity. Professor Liu pointed out that the data analysis for FCS is challenging and would require self-study by team members. Building a complete fluorescence detection system based on FCS components as described in the literature is impractical within our constraints. She advised us to seek alternative solutions or utilize existing fluorescence detection instruments.

July 15th, 2025

Following our discussion with Professor Yifan Liu, we recognized the need for a more practical fluorescence detection method. To understand the specifics of how our microfluidic chip specifications could be compatible with fluorescence detection instruments, we held a meeting with teachers Li Xiaoming and Xiong Ying on July 15th. Teacher Li Xiaoming is the Director of the Molecular Imaging Platform at ShanghaiTech University, and she is also a principal engineer. Professor Xiong Ying is the Director of the Molecular Cell Platform at ShanghaiTech University. Both have deep expertise in existing fluorescence detection technologies and the distinctions between different techniques.

Teacher Li Xiaoming
Professor Xiong Ying
Discussion Points:
1. Introduce the Gold Standard for Affinity Detection - Surface Plasmon Resonance (SPR) as a Control Validation
After understanding the team's needs and initial concepts for fluorescence detection, the two teachers identified a gap in our proposed approach - the lack of an objective, quantitative standard for control validation. Affinity is a key parameter measuring the strength of molecular interactions, and the teachers pointed out that SPR is currently a recognized, mature gold standard for determining affinity (KD values), recommending it as the benchmark method for project validation. We decided to use SPR technology to obtain precise affinity data for control verification.
2. Fluorescence Correlation Spectroscopy (FCS) Technology Poses Excessive Hurdles
In our original concept, FCS is a powerful technique that can measure molecular size, concentration, and interactions by analyzing fluorescence fluctuations at very low concentrations, theoretically making it well-suited for small-volume detection like in microfluidic chips.
However, the two teachers raised significant concerns:
High Barriers Faced: Teacher's Suggestion:

3. More Practical Fluorescence Detection Methods - FRET and MST
The teachers then discussed the practical requirements of another fluorescence detection method we initially considered - Fluorescence Resonance Energy Transfer (FRET) - and, drawing on their deep understanding of different detection technologies, introduced us to another more practical and effective fluorescence detection technique - Microscale Thermophoresis (MST). However, we ultimately did not use these two techniques because their detection accuracy and protein concentration requirements were not suitable for our project.

Participation with Clinician

July 8th, 2025

coffee
Professor An Guanghui

Based on comprehensive literature review, we have acquired a comprehensive understanding of the diagnostic and therapeutic protocols for chronic rhinosinusitis. However, recognizing that there may be discrepancies between these established theories and actual clinical practice, we sought to gain deeper insights into chronic rhinosinusitis.
To achieve this, we interviewed Professor An Guanghui from the Acupuncture and Tuina College of Shanghai University of Traditional Chinese Medicine, who simultaneously serves as a clinician with extensive experience in treating numerous rhinosinusitis patients.

Discussion Points:

1. Existing diagnostic and therapeutic guidelines for rhinosinusitis, and their disadvantages
Current diagnosis lags far behind the disease progression. When utilizing current diagnosis technology, such as a CT scan, late diagnosis and misdiagnosis often occur, and the technology itself has side effects. In the case of treatment, current treatment options for rhinosinusitis include nasal irrigation, use of corticosteroids or antibiotics, etc. However, all these approaches still have rooms for improvement.

2. The role of traditional Chinese medicine in the field of treating chronic rhinosinusitis
‘Traditional Chinese Medicine (TCM) holds distinctive advantages in treating rhinosinusitis, particularly for patients with recurrent cases resistant to conventional medications. TCM has addressed rhinosinusitis since ancient times. For example, leveraging the principle of the "lung-nose reflex", acupressure massage around nasal points expands lung alveoli to enhance respiratory function. Other techniques include massage to stimulate lymphatic circulation or targeted percussion to oscillate and directly expel mucus from the maxillary sinuses – all serving therapeutic goals for rhinosinusitis.’

3. Those misunderstandings——where communication and promotion kick in
Misconceptions about rhinosinusitis are so widespread that more education facing the public is urgently needed. For instance, chronic rhinosinusitis requires regular follow-up visits to monitor recurrence, yet fewer than 20% of patients demonstrate such awareness of follow-up care.’

August 21st, 2025

coffee
Director Li Zhiling

As is known to all, traditional Chinese Medicine and Western medicine differ significantly in their specific approaches to treating rhinosinusitis, and Western therapies continue to be the primary treatment modality worldwide.
To further elucidate Western medical strategies for the diagnosis and treatment of chronic rhinosinusitis, we interviewed Director Li Zhiling, who is an expert in treating this disease. She provided valuable insights into contemporary Western medical practices regarding this condition.

Discussion Points:

1. ‘We were particularly intrigued by whether high eosinophil levels, which strongly correlated with GZMK, were specific to eosinophilic chronic rhinosinusitis or applicable to all rhinosinusitis subtypes. To be brief, can our project address all kings of rhinosinusitis?’
‘Inflammation is inherently part of the diagnostic definition of rhinosinusitis; therefore, GZMK secretion theoretically represents a common manifestation across all rhinosinusitis types, so targeting GZMK activity inhibition could indeed serve as a therapeutic approach for all rhinosinusitis variants’

2. Project Spin-offs: Feasibility and Challenges in Implementation
An appropriate delivery system should provide moderate drug concentrations. However, translating a pharmaceutical project into practical applications requires significant time and funding, even though the project holds substantial potential for further development. It is really a long and arduous process with high failure rate.

Community Engagement

Engagements

June 2025

On June 28th, fourteen members of the ShanghaiTech-China team traveled to Suzhou to attend the 2025 Jiangsu-Zhejiang-Shanghai iGEM Regional Meet-up held at Xi'an Jiaotong-Liverpool University.

The conference commenced with a keynote speech by Dr. Bao Yuhan. Serving as both an iGEM 2025 Liaison and the Human Practices Committee Coordinator, he not only reiterated the core principles of the iGEM competition but also emphasized the crucial role that the Human Practices (HP) department should play—bridging the team and society. He highlighted that HP should enable projects to extend beyond the laboratory and facilitate two-way interaction with societal stakeholders. By engaging in thorough and in-depth exchanges between team projects and stakeholders, feedback should be utilized to continuously refine the project design, thereby creating a positive feedback loop that helps the project evolve iteratively. Dr. Bao's sharing provided us with invaluable insights.

During the conference, our team engaged in in-depth exchanges with teams from Fudan University, Xi'an Jiaotong-Liverpool University, and Jiangnan University through both oral presentations and poster sessions. These interactions not only enhanced our understanding of other teams' projects but also provided valuable new perspectives for our own work.

August 2025

From August 6th to 8th, six members of the ShanghaiTech-China team traveled to Beijing Zhongguancun to participate in the 2025 Conference of China iGEMer Community (CCiC). The CCiC is a national exchange conference independently initiated by iGEM teams from China, aimed at promoting mutual learning and communication among iGEM teams.

At the conference, the team presented this year's project—DOCTOR (Diagnostic Optimization & Chemical Treatment Of Rhinosinusitis)—to all attending iGEM teams from China.

Meanwhile, team members also engaged in in-depth discussions with students from other teams at the poster session, focusing on specific project details such as diagnostic and therapeutic approaches, as well as the design strategies for binding proteins. Throughout the CCiC event, our team established close connections and maintained active exchanges with institutions including Shanghai Jiao Tong University and Jilin University. These interactions not only provided fresh inspiration for our protein design models but also laid the foundation for potential inter-team collaborations, particularly in areas such as education and outreach.

During our discussions, we found that many team members from other groups also lacked awareness of rhinosinusitis, confusing it with rhinitis. It was only after we explained that rhinosinusitis originates in the cavities within the skull that they suddenly understood the distinction.

We also met two individuals who had previously suffered from rhinosinusitis. Due to their lack of awareness at the time, they delayed treatment until the disease had progressed to nasal polyps, requiring surgical removal—a process they described as extremely painful. They were eager to engage with us upon learning about our rhinosinusitis project, and they felt it was highly meaningful.

On the microfluidics side, we exchanged ideas on design considerations, including the Reynolds number in cell-free systems and the choice between laminar flow and droplet-based approaches.

ccic

Specifically, in our discussions on the software side, we delved deeply into the following core topics:

  1. the application potential and effectiveness of discrete diffusion models in protein/peptide sequence modeling, which forms the computational foundation for our de novo design of binding proteins;
  2. efficient training methods and reinforcement learning approaches for discrete diffusion models;
  3. the application of reinforcement learning in the field of AI for Biology;
  4. the application and balance between information-driven and theory-driven paradigms in biomacromolecular modeling.

These exchanges have provided substantial inspiration for the optimization of our software components.

Patient Voice

Background

Our entire diagnostic and therapeutic framework is supported by a human-centric principle. Aiming to deliver early diagnosis and precision therapy for chronic rhinosinusitis, our first step involved a thorough investigation of patient-specific requirements. We conducted structured interviews with six patients across different age groups to elicit detailed feedback on obstacles they encounter during their clinical journey and their anticipations regarding our project.

Discussion

  1. Level of knowledge about Chronic Rhinosinusitis
    One adult patient and three parents of pediatric patients, who themselves or whose children suffer from severe rhinosinusitis, had developed a considerable understanding of the disease. In contrast, the other two individuals had limited awareness of the pathology and consequences of rhinosinusitis before our communication.
  2. Specific needs for improving the diagnosis and treatment of Chronic Rhinosinusitis
    All patients unanimously expressed a strong desire for our treatment approach to minimize the recurrence of chronic rhinosinusitis. Beyond this common goal, specific needs emerged: one adult patient emphasized reducing medication frequency and improving the user experience of drug delivery, while a pediatric patient's family prioritized avoiding surgical intervention whenever possible. Regarding diagnostic methods, the paramount demands were convenience, non-invasiveness, and the development of at-home monitoring capabilities.
  3. Concerns and suggestions regarding our project
    One patient, who is also a healthcare professional, provided a more specialized perspective on our diagnostic and therapeutic approach. She expressed that for the general public who may not understand the project's underlying principles, relying solely on a single test strip indicator might not be convincing enough for a definitive diagnosis. She suggested that our test strip should primarily serve as a tool to alert individuals to their potential risk of sinusitis, encouraging them to seek further, more accurate and clinically feasible examinations at a hospital if risk is indicated. Additionally, regarding our small-molecule drug, despite its potential for precision therapy, she leaned towards trying conventional treatments first due to safety considerations.

Result

The interviews revealed several key points we had not previously anticipated, offering valuable guidance for our project's future direction. Beyond safety, efficacy stands as the foremost expectation for our small-molecule therapeutic. Patients also hope the treatment can reduce recurrence rates and dosing frequency. In summary, they hold significant expectations for our early diagnostic and precision therapy, believing it has the potential to effectively complement existing methods and address their shortcomings. Given the current lack of public awareness about chronic rhinosinusitis and its harms, we plan to launch education initiatives via short videos. Additionally, we are committed to fulfilling patient needs and broadening the application prospects of our project.

Growth Potential of Our Project

Our project covers the diagnosis and treatment of rhinosinusitis. Based on the screened high-affinity GZMK-binding proteins, we have developed a kit for the early diagnosis of rhinosinusitis. At the same time, we have also designed a platform for the rapid screening of small-molecule inhibitors. Both products hold significant commercial potential.

The core products or technologies of SynMetabio and Atantares are closely related to synthetic biology. Additionally, Dr. Yiming Dong, co-founder of Atantares, and Rui Su, CEO of SynMetabio, both have extensive experience in participating in and guiding iGEM competitions. To further explore the value and applications of synthetic biology in modern society, as well as to better understand the future translational potential and market prospects of our project, we conducted in-depth discussions with Dr. Yiming Dong, co-founder of Atantares, and Rui Su, CEO of SynMetabio.

August 2025

Since Atantares also extensively employs microfluidic technology, our discussion with Dr. Dong Yiming primarily focused on the feasibility and design approach of integrating chip-based microfluidics, MEMS, and CMOS at Atantares. We also explored the viability of current protein design strategies with Dr. Dong. Finally, we gathered suggestions regarding project presentation.

Discussion Points:

1. Project Presentation - Emphasize Logic and Readability in Web Presentation
After reviewing the initial version of our presentation page, Dr. Dong pointed out that when creating the wiki, it is essential to articulate key content clearly and in detail. More importantly, the logic behind the project narrative must be coherent, as only a well-structured story can make it easier for the audience to follow.

2. Potential for Hardware Optimization
We introduced the microfluidic technology used in our project to Dr. Dong. Learning that Atantares' product development also involves microfluidics, we inquired about its fundamental principles, which provided significant inspiration for our project:
Atantares integrates microfluidics, MEMS, and CMOS, utilizing electronic driving to manipulate droplets of varying sizes on PCB/silicon chips. This enables a fully integrated process of short-chain synthesis, purification, and assembly, showing considerable potential in throughput and cost efficiency. However, Atantares' approach relies on IC design, MEMS processes, and microfluidic control strategies, which could serve as a long-term improvement direction or reference architecture for our project.

3. Protein Design Strategy - Pursue Both Novel and Traditional Approaches, Adopting Industry Standards for Comparison
We presented two strategies employed by our team in designing binding proteins - a conservative route and an innovative protein design methodology. Dr. Dong recommended advancing both approaches concurrently, albeit with varying scales of wet-lab experimentation: traditional methods may undergo small-scale validation, while the novel approach warrants larger-scale trials to demonstrate feasibility. Additionally, he suggested that while developing GZMK-binding proteins using the new method, it would be beneficial to conduct comparative validation using the widely recognized BenchBB standard in the field. This would facilitate reviewer comprehension and enable benchmarking against peer studies.

September 2025

To further assess the technical feasibility and commercial potential of our project from a business perspective, we held an in-depth discussion with Rui Su, CEO of SynMetabio. We gained practical experience and constructive suggestions regarding project presentations to potential partners and possible future commercial translation.

Discussion Points:

1. Project Introduction and Presentation - Keep it simple, intuitive, and combine text with visuals
The page should adopt a clean and concise style. Language should be reviewed by a single person to ensure consistency in tone. Visuals are superior to text, but excessive dynamic elements and cluttered artwork should be avoided.

2. Experimental Data Retention - Maintain and present experimental results comprehensively, intuitively, and traceably
Use hand-drawn or intuitive diagrams in the design and results sections to clearly present experimental workflows and concepts.
And as for experimental records should completely preserve data and results from the experimental process in the form of images and tables to facilitate subsequent tracing and analysis.
Whatsmore, the detection kit might be unfamiliar to some audiences. Use diagrams or videos to intuitively demonstrate its usage method.

3. Commercial Translation - Both the project itself and market demand play important roles
Commercial translation is a two-way selection process. The project itself needs to be sufficiently attractive, while also requiring a suitable market to apply its outcomes.
Assessing market conditions requires considering market size, competition level, and future potential. Future potential includes not only technological advancements in the field but also alignment with national strategies.
If there are currently no competitors in the target field, it is essential to understand "why no one is doing it"