Contributions

Wet lab contributions

This year, our team set out not only to tackle therapeutic challenges in synthetic biology but also to strengthen iGEM as a competition and as a community. Each of our contributions was designed to be standardized, reusable and accessible, so that future teams can build on our work without starting from scratch.

Precise control in a minimal footprint

Most inducible systems use the minimal CMV promoter with Tet operators, but this setup is leaky and usually requires multiple plasmids.

We chose a different path: the TetO/YB_TATA promoter, a compact alternative that could, for the first time, place TetO and rtTA on a single vector. To our knowledge, it has not been used in published research outside iGEM.

By adding it to the Registry, we give future teams the chance to test its leakiness and performance and to explore whether it can truly simplify inducible design. If successful, this part could reshape how doxycycline systems are built, offering a cleaner, single-vector option where current systems fall short.

Unlocking compact parts

We introduced an ultra-compact doxycycline-inducible promoter (TetO/YB_TATA) that provides tight, tunable gene expression control while occupying minimal DNA space. Its compactness makes it ideal for size-restricted systems like AAV, but its utility extends across many fields.

In mammalian cell engineering, inducible promoters enable researchers to switch genes on and off with precision, making them reliable tools for studying disease pathways or modeling dynamic processes¹. In therapeutic contexts^2,3 such as CAR-T cells, they can function as “safety switches”, giving clinicians precise control over effector genes with a simple drug^4,5. In regenerative medicine, timed induction prevents harmful overproduction of growth factors-for example, doxycycline-regulated BMP expression has been used to control bone regeneration in vivo^6,7,8.

In developmental biology and stem cell research, induction ensures that critical genes are expressed only at the right stage of differentiation^9,10,11.

For the first time, this compact TetO/YB_TATA promoter has been standardized and added to the iGEM Registry, giving future teams a compact yet reliable tool for precise control of gene expression-from basic research to regenerative medicine and next-generation therapies¹².

Building backbone launchpads

Our dual-vector co-transfection system implements an AND gate requiring simultaneous cumate and doxycycline inputs for gene activation. This platform surpasses conventional overexpression or knockdown studies by enabling fine temporal and dosage-dependent modulation of cooperating genes. It is particularly suited for dissecting gene-gene interactions critical in tumorigenesis and fusion-oncogene biology. The system’s modularity supports integration of shRNAs, permitting temporally controlled knockdown/rescue assays for mechanistic insights and therapeutic development across neuro-metabolic and oncogenic contexts.

Cracking the visual AND gate

To make our work directly useful, we designed three versatile backbone plasmids as ready-to-use community platforms:

A constitutive backbone expressing a validated miRE-shRNA against HDAC6, paired with EGFP and puromycin for immediate experimental use.

Two dual-inducible backbones (cumate/doxycycline) equipped with fluorescent reporters and modular cloning sites, enabling safe, combinatorial gene expression experiments.

These backbones are not tied to our project alone. They can be adapted for RNAi projects targeting disease-linked genes, for logic-gated circuits^13,14 or for basic research in areas such as neurobiology and oncology, where precise and flexible gene control is essential.

Unleashing dual-inducible systems

Unlike transposon-based systems such as PiggyBac, which rely on transfection and perform poorly in non-dividing or primary cells, our lentiviral approach ensures stable integration and robust performance even in hard-to-manipulate contexts. The system supports both gene activation and repression, with the flexibility to incorporate shRNAs for temporally regulated knockdown. This also enables knockdown/rescue experiments, where an endogenous gene can be silenced while a wild-type or variant form is reintroduced in a controlled, stage-specific manner. By combining stable delivery with fine temporal and dosage control, the system provides a versatile framework for studying cooperative or context-dependent gene functions, advancing applications from basic biology to therapeutic discovery.

Democratizing control systems

We built a dual-input AND gate requiring both doxycycline and cumate to activate, moving beyond single-promoter regulation. This modular design opens the door to multi-layered logic in genetic control and can be adapted for shRNAs, therapeutic payloads, or mechanistic studies.

To ensure accessibility, we also developed a visual AND gate. Instead of relying on costly assays, this circuit produces a purple fluorescent signal when both inputs are active. This means even small teams can explore multi-layered regulation-a capability usually reserved for well-funded labs.

Simplifying RNAi

Beyond plasmid design, we validated a miRE-based shRNA targeting HDAC6 and submitted it as a ready-to-use part. HDAC6 is known to be overexpressed in several human diseases, including cancers (glioma, breast, lung, colorectal) and neurodegenerative disorders.

To guide future teams, we linked directly to HDAC6’s MalaCards page, where they can explore the diseases in which HDAC6 is overexpressed, the signaling pathways it is involved in and the potential therapeutic contexts where targeting HDAC6 could be valuable. This means teams can use our shRNA as a starting point to design therapeutic models or disease-focused projects wherever HDAC6 plays a pathological role.

Delivering validated miRE RNAi

We designed and validated a miRE-based shRNA targeting HDAC6, submitted as a ready-to-use part in the Registry. Embedding the shRNA in a microRNA scaffold camouflages the construct in the cytoplasm, ensuring efficient incorporation into the RISC complex while reducing immune activation. Compared to conventional shRNAs, this strategy improves intracellular half-life, lowers off-target effects and preserves cell viability, making it a robust platform for therapeutic or mechanistic studies where gene silencing must be precise and reliable.

Expanding the RNAi backbone

To maximize reuse, we placed the shRNA within a modular plasmid backbone that can be easily customized for new targets. Teams can swap the targeting cassette via restriction sites or cloning modules, enabling RNAi applications across many disease-linked genes. Practical guidance is provided to streamline this process: candidate target sequences can be identified using the Broad Institute’s GPP portal, while our design notes outline how to optimize scaffold choice and expression tuning. By combining modular cloning with clear instructions, this backbone serves as a flexible launchpad for future RNAi-based iGEM projects.

Shaping the future of therapeutics

Our contributions extend beyond our project to strengthen the iGEM community. By adding standardized parts to the Registry, providing modular backbone plasmids, developing accessible dual-input circuits and contributing validated RNAi tools with clear design guidelines, we created resources that are immediately reusable by future teams. These tools lower technical barriers, accelerate project development and open the door to more ambitious applications in therapeutic and fundamental synthetic biology. Above all, they reflect the iGEM spirit of sharing and openness, ensuring that future teams start from a stronger foundation and push the field further.

Dry lab contributions

Our team focused on the computational and theoretical aspects of our project, developing models and frameworks to support experimental design and optimization. Through simulations, data analysis and modeling, we gained a deeper understanding of the dynamics and behavior of our biological systems, allowing us to refine our designs and improve their overall efficiency. By thoroughly documenting our workflow and sharing our modeling approaches, we aim to offer future iGEM teams useful resources and a reliable foundation to build upon for their own computational studies and project development. To learn more about our Dry Lab work, visit our Model page.

Human practices contributions

As part of our Human Practices efforts, our team aimed to leave a lasting impact on both society and the iGEM community. We designed initiatives and integrated elements that future participants can learn from, adopt and build upon, creating projects with even greater impact. Our continuous efforts this year leave the following legacy in the competition:

Commitment to sustainable development

Our team aligned every aspect of our project with the United Nations Sustainable Development Goals (SDGs), actively addressing ten of them. By demonstrating that science can directly serve society and the goals it sets for its own development, we show that science can be both social and accessible, highlighting its profound societal impact. Our commitment to the SDGs is intended to inspire future iGEM teams, proving that a project does not need to address an environmental problem to fully align with these goals, as is often assumed.

Communicating synthetic biology

To engage students with ethical issues in science, we developed an interactive Bioethics Debate Card Game. The game allows students to discuss real-world dilemmas in synthetic biology, express their opinions through voting and reflect on the societal impact of scientific advances. It is freely accessible, enabling future teams to incorporate it into their outreach strategies and expand the reach of synthetic biology.

Download the game here

Many communities with diverse backgrounds often lack equal access to scientific and research knowledge. To ensure our project was holistic and accessible to all members of society, we recognized the need for tailored strategies. We therefore designed a Community Outreach Guide to serve as a practical tool for teams planning community engagement initiatives. Future teams can use this guide to ensure that their contributions are meaningful and genuinely beneficial to the communities they aim to reach.

Download the guide here

Destigmatization

Obesity is often misunderstood as a matter of personal failure rather than a complex, multifactorial disease. To address this, we created a Guide for Inclusive and Respectful Language in collaboration with mental health professionals. The guide highlights how the words we use in science and medicine carry weight and provide strategies to prevent stigmatizing language. Future iGEM teams can use it as a roadmap when communicating with patients or expand it with insights from other health conditions.

Download the guide here

Digital tools

Acknowledging the power of technological tools, especially in today’s digital era, we developed Healthy Byte, an application for children and parents designed to educate and promote healthy lifestyles. The app includes fun, gamified activities, nutrition guidance, weekly challenges, a supportive parent community and progress tracking with personalized feedback. Future teams are welcome to expand and enhance the application, supporting children and parents in acquiring essential knowledge about healthy living.

Workshop “Health & Ethics” impact questionnaires

To ensure that our workshop “Health & Ethics” created measurable change, we designed pre- and post-session questionnaires in collaboration with educators and mental health professionals. These tools assess shifts in students’ knowledge, attitudes and empathy across nutrition, mental health and social justice. By openly sharing the questionnaires, we provide future iGEM teams and schools with a ready-to-use evaluation method that can be replicated, adapted or expanded for different contexts. This contribution strengthens the link between science outreach and evidence-based impact assessment.

Download the pre-workshop here
Download the post-workshop here

Linking well-being with community health

Blood donation is more than a medical act, it is a powerful entry point to discuss the connections between nutrition, mental well-being and community health. To highlight these links, we created a Practical Guidebook featuring accessible explanations, everyday checklists and a “Myths vs. Facts” section about blood and donation. The guide was developed with input from nutrition and mental health specialists to ensure both accuracy and sensitivity. It is designed to be low-cost, scalable and freely available, enabling educators and future iGEM teams to integrate blood donation into broader health education initiatives. By openly sharing this guide, we provide a resource that can be replicated and expanded—linking scientific literacy with empathy, social responsibility and healthier everyday choices.

Download the Practical Guidebook here

Entrepreneurship contributions

Our team aimed to translate Morphe from a scientific concept into a real-world therapeutic solution. Early participation in entrepreneurship programs helped us cultivate a mindset focused on applying research to real needs, while enhancing our pitching, teamwork and strategic thinking skills. Through this process, we learned how innovation can be transformed into tangible societal impact.

We tested and advanced our project through participation in competitions together with accelerator programs, including Ideathon Patras, the Piraeus Bank Accelerator Program and the iGEM Startups Summer School 2025. These experiences provided structured feedback, helped us refine our strategies and enhanced our understanding of entrepreneurship in the biomedical field.

Through this process we:

• Applied Lean Business Model Canvas, SWOT analysis, PESTEL analysis, competitors analysis, Gantt charts together with financial roadmaps to craft a comprehensive business and market strategy.
• Researched drug development timelines together with regulatory approval processes, identifying which steps a student team can realistically undertake and the type of institutional and industrial support required.
• Developed financial projections, risk analyses together with regulatory outlines, creating resources that can serve as templates for future iGEM teams, especially for therapeutic projects.
• Collaborated with clinicians together with industry professionals to validate Morphe’s feasibility and strengthen its translational relevance.
• Promoted social and ethical responsibility, ensuring safety, equity and sustainability while raising awareness on obesity together with metabolic health.

The deliverables, frameworks and methodologies created by our team provide a practical model for future iGEM teams, helping them navigate realistic timelines, regulatory requirements and identify the support networks essential to successfully translate scientific research into real-world applications. All of the above can be viewed on our Entrepreneurship page.

Finance contributions

One of the greatest challenges our team faced was securing the financial resources required for our iGEM participation. From the registration fees and laboratory consumables to event organization and outreach activities, funding was a constant challenge. Due to limited internal funding, our university could not cover the competition expenses, so we took full responsibility for approaching external companies, institutions and organizations that believed in our vision and decided to support us.

This process, although demanding, taught us how to communicate effectively, pitch our idea with confidence and build meaningful partnerships.

A key factor in our success was the Sponsorship Booklet we created, a comprehensive document outlining our mission, activities, budget and sponsorship packages. It became a professional presentation tool that helped us demonstrate the value of our work and attract sponsors.

To contribute to future iGEM teams, we decided to share our Sponsorship Booklet template. This resource serves as a practical guide for teams aiming to secure financial support, providing a structure that clearly presents their project’s impact and value to potential sponsors. We hope that by sharing this, we can make the fundraising journey easier and more efficient for future iGEMers.

Download Sponsorship Booklet template

Graphic design contributions

Science is best understood when it’s seen. To empower future iGEM teams, we developed a graphic design archive featuring editable illustrations of biological pathways, experimental designs and wiki-ready materials. Compatible with Adobe Illustrator and similar tools, this resource is freely available to customize, helping teams bring their scientific stories to life with clarity and creativity.

Download the Graphic Design Archive here