Great success for the iGEM Freiburg team at the Grand Jamboree in Paris 2024

The growing threat of antibiotic resistance and an innovative solution: CAPTURE

Antibiotic resistance is associated with three million deaths worldwide every year. But estimates predict that by the year 2050, this number could rise to ten million, which is comparable to the current number of deaths caused by cancer. So this is already a significant issue and will become an even bigger concern in the near future. An especially serious threat comes from the ESKAPE pathogens – a group of bacteria notorious for evading antibiotic treatments. This year's iGEM project CAPTURE was designed to CAPTURE the ESKAPE pathogens, or more specifically, one of them: Pseudomonas aeruginosa, the major cause of ventilator-associated pneumonia.

To replace antibiotics, we implemented antimicrobial peptides (AMPs)—evolutionarily conserved effectors of the innate immune system. By binding to bacterial membranes, AMPs cause pore formation and disrupt membrane integrity, making it much harder for bacteria to develop resistance.

To circumvent the production costs and poor pharmacokinetics that come with AMPs, we encoded the peptide on a plasmid for delivery to, and expression in the target bacteria itself. Basically, at the site of infection, P. aeruginosa is transformed to produce AMPs and self-destruct.

Vesicular Carrier Systems for targeted delivery of plasmids into the bacteria

For the delivery of the plasmid, we explored two distinct vesicular carrier systems in parallel: Lipid Nanoparticles (LNPs) and Outer Membrane Vesicles (OMVs).

Lipid Nanoparticles (LNPs): These lab-produced vesicles (50-500 nm) use synthetic lipids. By fine-tuning lipid composition and surface modifications, characteristics like payload capacity, stability, and target specificity can be optimized.
Outer Membrane Vesicles (OMVs): are naturally secreted by gram-negative bacteria (20-200 nm) and play an important role in horizontal gene transfer and stress responses. We employed a modular SpyTag/SpyCatcher system, making use of a phage tail protein, for specific targeting of P. aeruginosa.

Graphical abstract. The antimicrobial peptide (AMP) is encoded on a plasmid with a pseudomonas-specific promoter (pel). Transport of the plasmid is mediated by target-specific vesicles, which fuse with Pseudomonas aeruginosa. The bacteria express the AMP and are killed from within.

The Grand Jamboree in Paris: Project presentation and making connections and lasting memories

In October 2024, our team of fourteen members, supported by three supervisors and two principal investigators, traveled to Paris for the Grand Jamboree. This four-day event at the Parc des Expositions brought together synthetic biology teams from around the world to present projects, engage with judges, and network with academic and industry experts.

iGEM from above. Image: iGEM Foundation, (CC BY 2.0)

We showcased our work at our information booth and delivered a live stage talk on integrating ethics and innovation into combating Pseudomonas aeruginosa. Of course, we also explored the other teams' projects and connected with iGEMers from around the world. We made lasting memories—from a spontaneous table football tournament with other teams, to team celebrations on the sun deck, and evenings spent exploring the city.

Judging Day: Rising to the occasion

The third day of the Jamboree was critical: Judging day. Each team promoted their project at their info booth and attended a formal judging session. We delivered a concise five-minute pitch, summarizing the core of our project, followed by a twenty-minute Q&A with the judges. Despite the pressure, we rose to the occasion and in the evening, celebrated the conclusion of the Judging Sessions with other teams – soaking up the excitement of being in Paris with so many others whose creativity and hard work had brought them here.

Awards and achievements

On the final day, we were thrilled to be ranked among the top 10 Overgraduate* teams and to win the Best Infectious Disease Project award. We were also nominated for several Overgraduate Special Awards, including:

Best New Composite Part
Best Measurement
Best Integrated Human Practices
Best Presentation
Best Wiki

This recognition validated the dedication and effort we invested throughout the year.
* Overgraduate means that at least one member of our team is over the age of 23 or has a university degree.

The iGEM Team Freiburg 2024 with the award for the Best Infectious Diseases Project. Top row from left to right: Leon-Samuel Icking, Niels Geipel, Liv Neumann, Isabelle Tipp, Emil Kozma, Alexej Wolosski. Middle row from left to right: Dr. Pavel Salavei, Lucille Gutzmer, Dr. Nicole Gensch, Amelie Stange, Laura Pasman, Marina Hammerl. Bottom row from left to right: Leonie Mungenast, Jan Zielinski, Mathilda Bertges, Nicole Kucera, Nafis Madappalli, Melita Dyla, Ivana Rozić. Image: iGEM Foundation, (CC BY 2.0)

Acknowledgments and Gratitude

Our success was made possible by our Principal Investigators, Dr. Nicole Gensch and Dr. Pavel Salavei, whose dedication and support were crucial to our team's success. We are deeply grateful to them, as well as to our student supervisors: Melita Dyla, Anne Frederiksen, Leon-Samuel Icking, Anna Indricane, Konstantin Jaeschke, Yara Jenin Jamal, Jonas Pleyer, Kevin Postol, Michael Spädt, Amelie Stange, and Hannah Swientek.

We would also like to express our gratitude to our main sponsors – the University of Freiburg, CIBSS and BIOSS – as well as the many laboratory groups, in particular the Römer Lab, and their members, who have generously supported us with material donations and with valuable expertise.

This year was more than just a research project for us – it was a dynamic journey full of challenges, learning and team spirit, and we are excited to see what ideas the next iGEM team will develop in 2025.

Written by Liv Neumann, member of the Freiburg iGEM team of 2024.