Our project: CONCAVE

Every year, iGEM brings together hundreds of teams from around the globe in Paris to exchange ideas on how synthetic biology can be used to solve real world problems and shape a better future.

In 2025, Team Freiburg presented CONCAVE, a project designed to revolutionize the production of novel antibodies, essential tools for countless laboratory applications. Today, generating custom antibodies is expensive, monopolized by specialized companies, and still heavily dependent on animal immunization. This not only raises ethical concerns, as animals are repeatedly used in the process, but also limits scientific progress. The lack of accessible alternatives and the reliance on costly, centralized production leaves many labs, especially those with limited funding, without the reagents they need.

CONCAVE aims to change this.

We designed a system that enables researchers to generate custom protein binders as antibody alternatives directly in E. coli. Thus, making binder development faster, cheaper, and accessible to any lab.

Antibody alternative: learning from nature

CONCAVE is based on Repebodies, binders inspired by the Variable Lymphocyte Receptors (VLRs) found in the immune system of jawless fish. Like VLRs, Repebodies are composed of Leucine-Rich Repeats (LRRs), whose variable amino acids allow for a concave binding surface capable of recognizing diverse targets.

To achieve this diversity in vivo in E. coli, we introduce mutations directly into the Repebody-coding genes. Short single-stranded DNA (ssDNA) fragments carrying the desired mutations enter the cell and anneal to the DNA during its replication. After a few rounds of replication, these mismatches are locked in as mutations, generating a diverse library of Repebody variants.

To make the entire process possible, we investigated retrons, a bacterial defense mechanism against viruses that produce ssDNAs directly inside the cell. This allows the diversification system to work fully in vivo after transformation, without handling external DNA during the mutation step.

Finally, in order to select for the Repebody with the desired mutations, we have explored the bacterial adenylate cyclase two-hybrid (BACTH) system, which can detect protein-protein interactions. This allows us to screen large cultures and identify the Repebody that specifically binds to the protein of interest.

Repebodies unlock thousands of potential applications. In our project, we took the first steps toward targeted protein degradation by designing a chimeric construct that connects the Repebody to a degradation initiator. This would allow any protein of interest targeted by the Repebody to be pulled into the degradation machinery and be destroyed in the lysosome.

Furthermore, we also performed Far Western Blots using Repebodies as primary antibodies to prove their usefulness in antigen-binding assays.

If you would like to have a deeper understanding about our project and results, you can read all about it here:  https://2025.igem.wiki/freiburg/

Grand Jamboree: Ceremony, Awards, Presentations and Connections

In the last week of October, our team of 11 members, 5 advisors and 2 PIs boarded a train that would lead us to the final challenge of our iGEM journey: the Grand Jamboree in Paris.

The 4-day event gathered a crowd of almost 5000 participants, including students, researchers, industry representatives, nonprofit organizations and journalists.

Each team had its own booth to present its project to the other attendees. We organized ourselves in multiple shifts, guaranteeing that at least one member of each subgroup would be there to answer specific questions from the more curious participants. In the remaining time, off-shift members could wander around the huge venue, go to other team’s booths, and listen to live stage talks held by members of different teams.

Team member Keno Tellkamp delivered our stage presentation “The RNA Renaissance: Functional RNAs”, highlighting the diverse roles of RNAs and introducing the audience to retrons, the core of our mutation system.

Judging day: the final challenge

After two days of presenting and exchanging ideas, we were ready for our judging session.

First, we had to hold a concise five-minute pitch, summarizing and selling the potential of our project for one last time. The enthusiasm of the judges towards CONCAVE gave us the confidence we needed to successfully answer all of the questions about biosecurity, lab methods, literature and bioethics during the 20-minutes Q&A session. We left the judging room proud and relieved. All that remained was the award ceremony.

Awards and achievements: a day to remember

When sitting together at the ceremony, surrounded by thousands of participants, we truly felt the scale of iGEM.

The very first award to be announced in the ceremony was Best Basic Part. Suddenly, seeing FREIBURG appear on the giant screen and going on stage for the very first time in front of such a huge crowd felt unreal.

Later, it was time for the Village prizes to be announced. To increase the suspense, the moderators described each project before revealing the team’s name. It felt like a fever dream when we started hearing phrases like “…custom protein binders”  “…generated in E. coli” “…antibody alternative” - they were talking about us! Once again, FREIBURG was to be read on the big screen.

Once all 15 village prizes were announced, it was time for the “Best Veteran Judge”. This time, the screen did not show Freiburg, but rather the name Nicole Gensch, the PI who has guided Freiburg teams since 2014. One thing is for sure: the team was even more excited about this award than Nicole was. We cheered loudly as she walked onto the stage. It was now our time to be proud.

Then, the medals were revealed simultaneously for all teams. When Freiburg appeared under “Gold”, the higher level of excellence, we celebrated together with everyone around us.

Finally, the TOP 10 Overgraduate Teams were announced, and FREIBURG appeared on the big screen for the last time.

We ended that night with 4 awards and 2 nominations:

• Best Foundational Advance Project
• Best Basic Part
• Gold Medal
• Best Veteran Judge (Dr. Nicole Gensch)
• Nominations: Best Wiki, Best Presentation

*Overgraduate: at least one member is over 23 or holds a completed university degree.

Acknowledgements and Gratitude

This success was only possible thanks to dedication and collaboration.

We would like to sincerely thank our Principal Investigators Dr. Nicole Gensch and Dr. Pavel Salavei, for their endless patience, for teaching us that “bad” results are still results, for showing us lab techniques that go beyond what’s taught in books, and for motivating us to always strive for more.

We are deeply grateful to our advisors Michael Spädt, Amelie Stange, Isabelle Tipp, Ivana Rozić, Jan Zielinski, Nicole Kucera and Niels Geipel, for guiding us based on what they had learned by being members of previous Freiburg iGEM teams, as well as for their time spent in countless meetings with us.

We would like to thank Concepción Sainz Rueda (Conchi) and Efthimia Yousefi (Effi) for their support in the lab, and Sarah Kempff for the workshops that helped us grow as a team. And we say thank you again to Effi for always bringing us food, giving us the energy to work even harder.

Finally, we would also like to thank our sponsors, CIBSS and BIOSS, for providing us with a lab and materials.

iGEM Recap: more than a competition

We are deeply grateful to have participated in iGEM. It allowed us to understand the world of research, be inspired by incredible projects presented at the Grand Jamboree, and see students apply and piece together concepts taught in university that once felt so distant and abstract.

Beyond synthetic biology, iGEM taught us how to work in a team, to be resilient and organized (or at least a bit more organized), to ask for help, to motivate each other when facing failure, and how to collaborate across disciplines for a common goal.

We can’t wait to be amazed by the next team’s idea and to advise them based on everything we have learned.

Written by Ana Luiza Longo Moniz Freire, member of the Freiburg iGEM team of 2025,

Join the 2026 iGEM Team Freiburg

Would you like to be part of next year’s team as a member or advisor?

Submit your application HERE by 30 December 2025, 23:59 CET.