Medal criteria

Bronze Medal

Silver Medal

Gold Medal

Software

MESA Designer is a computational tool that automates the design of modular receptor systems for synthetic biology. It integrates antibody structure databases, transmembrane domains, and protease components to generate production-ready genetic constructs with full sequence optimization, restriction site avoidance, and standards compliance (RFC10, BioBrick, iGEM Registry), providing a web interface, REST API and a python package for flexible integration into design workflows.

Standards Integration

The software generates GenBank files compatible with industry platforms (Geneious, SnapGene, Benchling) and implements RFC10/12/1000 and BioBrick standards for restriction site avoidance. It integrates with established databases including SAbDab (10,000+ antibody structures) and SKEMPI v2.0 for binding affinity data. Check out our available inputs and outputs on our software page.

Software Validation

Built exclusively on experimentally validated components from peer-reviewed publications (TMDs, proteases, linkers, tags, AIPs, FRET sequences), MESA Designer successfully reproduces published MESA designs (FKBP/FRB rapamycin sensor, VEGF-sensing receptor, GFP-sensing design). The software is currently undergoing wet lab validation with two novel software-generated receptors (progesterone-responsive and IgG-responsive MESA). Read our validation section on our software page for more details.

iGEM Project Integration

The tool addresses the generalizable challenge of engineering modular receptors by separating design into universal components (binding domains, transmembrane anchoring, signal transduction, cargo release), enabling teams to rapidly prototype receptors for any ligand-receptor-response system. Automated FRET validation constructs and multi-organism optimization (human, mouse, etc.) demonstrate utility for varied experimental contexts. View examples of potential iGEM integration on our software page.

Software / Tool Integration

MESA Designer provides triple-interface architecture (web application, REST API with documentation, and Python package) with Docker containerization for deployment. Industry-standard file outputs and modular codebase enable extension with additional algorithms or databases. Further information about the architecture and extensibility is available on our software page.

User-Friednliness

Iterative user testing led to platform-specific instructions (Windows/macOS/Linux), comprehensive input validation with educational warnings, and visual feedback through color-coded annotations and real-time 3D structure previews. Accessibility across skill levels is ensured along every step from installation to integration into complete engineering environments using the python package or API. You can refer to our freely distributable PDF Instructions, video tutorials and our usage guide on our software page.

Future Contributions

The production-grade codebase features comprehensive inline documentation code documentation and clear separation of concerns (database interactions, sequence processing, UI rendering). We performed performance testing to ensure the software runs even on low-spec machines. To provide a concise overview of the software’s structure and data flow we provide clear architecture diagrams. Installation guides refined through user testing cover Docker/local deployment and troubleshooting, with version-controlled documentation including usage guides, API specifications, and design decision records for future contributors.

Integrated Human Practices

InkSight, as it stands today, is the result of challenging conversations, rigorous analysis, and genuine reflexivity. Every aspect of the project, from conceptual and experimental design to safety measures, software development, and communication strategies, has been continuously shaped by the many perspectives we engaged wth. Our Human Practices work was structured around a flipped pyramid, framework emphasizing diversity at three levels: stakeholders, methods, and feedback integration. This reflexive process not only informed our technical and ethical decisions, but it also refined InkSight’s current direction, aligning our motivations and activities with a long-term vision of responsible and context-aware innovation.

Integration throughout InkSight

From earliest conceptualization through final implementation, Human Practices shaped every major decision. Expert consultations with bioengineers, ethicists, dermatologists, and bioartists guided our understanding of fairness, safety, and aesthetic expression in a living tattoo system. Survey results directly determined biomarker targets (progesterone, troponin I, LL-37) and safety priorities. STIR protocols document how each consultation is connected to specific project decisions. Our Policy Analysis on ATMPs and the MDR defined our regulatory pathway and explored socio-ethical considerations in detail. In sum, our work shows integration was not a one-time check but an iterative process: each stakeholder interaction reshaped our assumptions and encouraged us to better tackle a different aspect of InkSight, ranging from wet lab strategies, construct designs, and software development to safety measures, regulatory positioning, and communication approaches.

Implementation and Rationale

Our Human Practices framework was intentionally designed to integrate diverse perspectives into each research phase. We conducted over 30 documented stakeholder meetings using the STIR (Socio-Technical Integration Research) framework, continuing the work of 2024's iGEM team, ensuring reflexivity about the different aspects that are present in our engagement activities. Key technical choices, including our focus on mammalian cells over bacteria, tyrosinase engineering strategies, MESA receptor design and software, biomarker target selection, and hydrogel requirements, directly resulted from expert consultations.

Beyond expert interviews, we deployed multiple complementary approaches: a quantitative survey (n=246) with Latent Class Analysis revealing distinct public safety perception profiles that deeply guided our Safety and Security, including the design and ongoing validation of a kill switch strategy. A public art competition bridging science and creativity, opening up collaboration with tattoo artists, and a comprehensive policy analysis examining ATMP/MDR regulatory frameworks, biosecurity concerns, and ethical implications. We engaged tattoo artists at conventions, consulted bioethicists on autonomy and justice concerns, discussed reimbursement pathways with health insurance representatives, and interviewed elderly cardiac patients to understand real-world user perspectives.

Desire to Motivate Others

Our flipped pyramid framework offers a replicable model for challenging assumptions at every level of Human Practices. We designed InkSight by confronting differing understandings of fairness, legitimacy, feasibility, ethics, and integrity, recognizing this work as a responsibility, not a competition requirement. At the stakeholder level, we questioned who shapes synthetic biology: engaging tattoo artists, elderly cardiac patients, and bioartists alongside academic experts revealed implementation realities invisible to technical analysis. At the methods level, we explored qualitative, semi-quantitative, creative, or future-oriented eagles for the integration of artistic, empirical, and policy perspectives. And at the integration level, we let not only the experimental and conceptual aspects, but also our outreach and, most importantly, our safety and security work be shaped by different socio-ethical considerations.

Documentation and Improvement

Every stakeholder meeting includes a detailed STIR protocol documenting context, decision points, and integration outcomes. Our survey methodology, which covers demographic data, GDPR compliance, LCA construction, limitations, and the full questionnaire template, is publicly accessible for replication. The policy analysis synthesizes regulatory, biosecurity, biosafety, and ethical dimensions into a standalone document informing our Safety and Security work. Patient interview protocols specify consent procedures and GDPR compliance. This comprehensive documentation provides reproducible tools, templates, and analytical approaches enabling future teams to build upon our methods, adapt our frameworks, and extend our findings across diverse synthetic biology applications.

Diversity of Stakeholders (and Methods and Feedback)

Our approach emphasized genuine dialogue and co-creation rather than token consultation. We engaged with over 30 stakeholders including laboratory scientists, clinicians, ethicists, patients, artists, and policymakers, systematically mapping them by interest and influence. Each meeting prompted reflection on underlying assumptions about safety, trust, and user autonomy, often challenging our initial, documented assumptions. Feedback was categorized into four dimensions: Science (tyrosinase engineering, MESA design, encapsulin assembly), Culture (bioartists challenging body autonomy framing, tattoo artists revealing implementation constraints), Anticipatory Governance (policy analysis examining biosecurity frameworks and ATMP classification), and Community (survey revealing safety concerns, elderly patients informing placement constraints with anticoagulants). All these differing perspectives fundamentally reshaped experimental design, safety frameworks, biomarker selection, and communication strategies across all project dimensions. In addition, our flipped pyramid framework shows how diversity of stakeholders was embraces via the experimentation with different methodological choices and feedback integration.

”Responsible and Good for the World”

Our Human Practices work demonstrates InkSight became fundamentally more responsible through systematic engagement with challenges often overlooked in synthetic biology projects. Beyond standard biosafety, we explored patient autonomy in non-removable diagnostics, privacy risks in contexts of reproductive control, and inclusivity concerns around melanin’s visibility across different skin tones, prompting alternative pigment research. We investigated implementation pathways, including hybrid medical tattoo studio models requiring novel certification frameworks, detailed ATMP versus MDR regulatory classification with precedent case analysis, and the artistic dimensions of functional body modification through bioartist collaborations and engagement with tattoo studios. Our quantitative survey employed rigorous statistical analysis and extensive consultation to avoid common acceptance-framed questions, prioritizing genuine understanding of safety perceptions while remaining aware of methodological limitations inherent in self-selected sampling. Our bias acknowledgement grounds the project in transparent recognition of techno-optimistic perspectives and unresolved ethical tensions that show the narrow-mindedness of overpromising in iGEM projects. These efforts reflect our commitment to responsibility and reflexivity as ongoing practices rather than completed achievements, acknowledging that meaningful engagement with societal complexities extends beyond any single project timeline.

Model

Modeling Overview integrates multi-scale computational approaches spanning enzyme kinetics, optical transmission, and structural biology to optimize melanin-producing nanocage systems. The work combines Michaelis-Menten kinetics for tyrosinase activity prediction, Beer-Lambert law modifications for optical properties of a hydrogel bead filled with modified HEK cells, and comprehensive structural modeling using SPELL, AlphaFold2, Boltz-2, and Rosetta Suite to engineer controllable tyrosinase variants and predict their assembly within encapsulin nanocages.
The modeling campaign systematically screened 19+ tyrosinase variants through integrated computational pipelines requiring candidates to pass stringent criteria across split site prediction, structure prediction, binding affinity estimation, and physics-based energy validation. Read more about our computational methods on our model page.

Project Integration

Computational predictions directly shaped experimental strategy at every decision point, transforming exhaustive screening into targeted hypothesis testing. The lid domain engineering for HcTyr1 relied entirely on computational identification of the likely auto-cleavage site and design of modified linkers, which experimental validation confirmed. Split tyrosinase candidates emerged through SPELL-identified optimal division points that AlphaFold2 validated would restore native active site geometry. View our wet lab impact on our model page.

Data Sources

All model parameters derive from experimentally validated sources with comprehensive citation. Kinetic constants (kcat, KM) for tyrosinase variants come from peer-reviewed publications. Copper coordination geometry references crystal structures from the Protein Data Bank. Structural modeling employed sequences from UniProt. Conservative assumptions (irreversible reactions, steady-state kinetics, negligible flux through nanocage pores) are explicitly stated with justifications, while experimental validation with Native PAGE analysis revealed that actual encapsulin tolerance exceeded conservative predictions.

Guideline for Future Modelling

The dynamic modelling components predict melanin production kinetics and optical properties across different tyrosinase-nanocage combinations. Michaelis-Menten differential equations with competitive inhibition terms model dopaquinone concentration over time for all tyrosinase-encapsulin pairs and were solved numerically via scipy. Modified Beer-Lambert law calculations predict hydrogel bead transmission as a function of nanocage concentration per cell, showing that SkMelC2+MX at maximal loading reduces transmission to 3.35% through a single bead. Explore our tyrosinase kinetics model and optical transmission model on our model page.