Human Practices
Integrated Human Practices is about connecting our project to the real world and understanding how it affects people and society. It’s not just a side task. It shaped our design and helped us to make responsible choices. To do this, we spoke with experts, stakeholders, and went to many meetups, even planned our own. Each conversation gave us new perspectives, challenged our assumptions, and showed practical needs we might not have considered. By listening and learning, we could adapt our project to be more useful, safe, and relevant. Next, we explain what we learned from these meetings and how it influenced our work.
Thanks to some great minds and enthusiastic supporters we were able to evolve our idea and our system of a condensate-based sensory system for RNA and actively discuss its need in the scientific world. Come with me to discover the history and development of TRAPS with the aid of countless experts in various fields!
I wonder what would happen if I clicked on the images...
In the process of finding our final project idea, we came across several other promising ideas first, which, after receiving feedback of experts of those fields, could be integrated and combined into the TRAPS system. Initially we considered using optogenetics to activate CAR T-cells only locally in order to reduce the side effects of CAR T-cell therapy. Our other most promising idea was to use condensates to boost the production of biopharmaceuticals by increasing the efficiency of enzyme cascades and enabling those with toxic or unstable intermediates. Following our innovative idea of using RNA to connect construct proteins of condensates, we quickly realized that we wanted to create an easier, more modular RNA sensory system for in vivo systems.
After and during our idea development phase, we started researching ways to implement our system in yeast, the organism most widely used by our mentors in the Aberti lab at the BIOTEC of TU Dresden. After consulting with countless experts, we were finally ready to start the wet lab work. Even after starting our experiments, we continued to integrate advice, alternative plans, in case something didn’t go as planned and improvement suggestions into our experimental designs.
In the absence of the right tools to select the optimal target RNA sequences for both our Cas13 system and our Pumby system, we developed our own software, SEA-STAR (side effect aware target site ranking), to assist with this task. Meeting with several bioinformaticians helped us to predict and calculate the perfect RNA target sequences with minimal off-target effects and optimal accessibility.
For many of us, as a group of young researchers and students, it was our first experience of organizing, presenting and implementing a project of this scale. This also involved communication, fundraising and public relations work in the scientific world. The many opportunities that have been presented to us by numerous professionals helped us to develop our system, our wiki and our new skills. We are now proud to present TRAPS to you.
Since we developed TRAPS with the intention of making it universally applicable to many organisms and target RNAs, we have contacted many renowned scientists to discuss further use cases that we have not yet come across. This has provided us with valuable constructive feedback on our system and a wealth of ideas for new practical applications that real scientists could use.
“At the Institute of Clinical Genetics Dresden, our team of physicians and scientists investigates the genetic origins of brain malformations and tumor development. The TRAPS system would be a powerful tool, allowing us to visualize the real-time expression of low-abundant, disease-causing RNAs. Observing precisely when these genes are active would provide critical insights into the mechanisms of disease formation.”
“At Bone Lab Dresden (www.bone-lab.de), we are researching the molecular and cellular mechanisms underlying osteoporosis, also known as bone loss. Loss of bone mass can occur due to age, various diseases, or medication use. With the TRAPS system, we would be able to examine changes in the gene expression profile of bone cells after treatment with, for example, medication in real time. In addition, the platform offers the possibility of modulating gene expression, which would allow us to investigate the significance of specific signaling pathways.”
“In my group at the Department of Pediatric Hematology/Oncology and the NCT/UCC Dresden, we aim to identify novel targets for individualized cancer therapy. To achieve this, it is often helpful to study the regulatory networks that drive tumorigenesis, especially when no direct inhibitors for a given target are available. In such cases, the TRAPS method can be used as a reporter system to identify therapeutic compounds that modulate gene expression in real time.”
“The TRAPS system looks like a potentially very useful system for live monitoring of transcriptional states in embryos and tissue, and clearly meets a demand for such a technology. My lab is interested in the mechanisms controlling the nervous system of the zebrafish to regenerate - something that we, as humans, cannot do. It would be great to further develop and adapt TRAPS for this work in zebrafish, and in my lab I would be glad to support this effort of the TRAPS team.”
"It is my pleasure to provide this letter of support for the 2025 iGEM team from TU Dresden. The team's research focuses on developing innovative tools to elucidate the mechanisms underlying neuronal degeneration and to facilitate the identification of novel therapeutic strategies. These are fundamental questions that are also central to our own research efforts, and the approaches being developed by the TU Dresden iGEM team address a critical and long-standing need within the neurodegeneration research community. Our laboratory is deeply committed to advancing methods for the precise detection and localization of RNA molecules within cells. In particular, we seek to understand how specific RNAs interact with their corresponding proteins—a core objective of our current and future work. In this context, the TRAPS approach proposed by the TU Dresden iGEM team is of particular interest. Its capacity to visualize the colocalization of proteins of interest with their respective RNAs represents a highly promising avenue for uncovering fundamental aspects of RNA–protein interactions. We view this project as both innovative and scientifically rigorous, with the potential to complement and enhance existing technologies in the field. The successful implementation of TRAPS could provide significant insights into cellular processes and contribute meaningfully to studies of RNA–protein dynamics and their implications in molecular neurobiology."
“One exciting research question where TRAPS could be extremely useful is understanding how host cells respond in the very first moments after infection. When a virus or bacterium enters a cell, it triggers rapid transcriptional changes, often only in a small fraction of cells and sometimes only transiently. With TRAPS, we could visualize the appearance of specific mRNAs in real time and at the single-cell level, allowing us to capture these early and short-lived responses that bulk RNA sequencing would completely miss. This could help us uncover, for example, which antiviral genes are switched on first, how pathogens suppress these signals, or how rare “first responder” cells shape the course of infection. A concrete research question where TRAPS could be invaluable is the study of how coronaviruses manipulate the unfolded protein response (UPR) in the host endoplasmic reticulum. It is known that viral proteins trigger ER stress, but the dynamics and timing of which UPR genes are activated remain unclear.”
“Designing a synthetic system that condenses in response to a specific RNA provides a highly responsive in vivo RNA detection strategy using the unique properties of cellular phase separation. If the TRAPS system proves successful it could become a powerful tool to be applied to many research questions.”
Our initial concept was to use biomolecular condensates to enhance enzymatic turnover by linking enzymatic cascades for improved pharmaceutical synthesis. This goal was very ambitious, which is why we consulted a team of experts on the possibility of achieving it in the given time and competition guidelines. We presented our concept to three biomolecular condensate specialists: Prof. Dr. Alberti, Dr. Franzmann and Prof. Dr. Honigmann.
The experts confirmed our concept was highly ambitious, but the talk sparked a productive discussion on alternative strategies. The experts suggested implementing a chaperone-assisted, cell-free expression system. Together, we started the idea of designing a condensate-based sensory system which could detect RNA in vivo with a high signal-to-noise ratio.
Although we thoroughly discussed how to implement an enzyme cascade for increased pharmaceutical production, we chose to pursue in vivo RNA detection as a more promising direction. This set the starting point for developing our TRAPS system.
At the beginning of our project, we came up with the idea of creating bioluminescent E. coli to optogenetically activate CAR T-cells once they had been driven to cancerous tissue or activated by its typically low extracellular pH levels. This would reduce the side effects of CAR T-cell therapy by only activating these modified immune cells locally, in tumor tissue. As this was a very ambitious idea, we contacted Prof. Dr. Dahmann, as an expert in molecular genetics and optogenetics, to help us refine it.
During our discussions with Prof. Dr. Dahmann, we learned about the basics of optogenetics, as well as challenges involved and possible approaches to resolving them. He confirmed that our idea was feasible, but difficult to implement due to the numerous experimental steps and the low light intensity of luciferase. If we wanted to use luciferase as a light source, it would need to be a very specific and high-output variant. To achieve intercellular communication through light signals, the luciferase should also be expressed as close to neighboring cells as possible, i.e. on the cell surface.
When further developing this idea, we created a concept involving high cell-surface expression of a luciferase with strong bioluminescence in E. coli by fusing it to a membrane protein. Using pH-sensitive promoters to control luciferase expression should result in light being emitted only at low pH-levels, such as in cancer tissue, to activate CAR T-cells.
We needed to find a relatively short and uncomplicated cascade to prove the increase in biopharmaceutical production through greater spatial proximity, which is achieved by locally upconcentrating enzymes of a specific cascade in condensates. We also needed to find a relatively short and uncomplicated enzyme cascade for our proof-of-concept experiment. Additionally, we wanted an expert to consult with us on our other idea of producing, normally chemically produced, pharmaceuticals with toxic or unstable intermediates also by locally upconcentrating the involved enzymes in condensates and immediately converting the intermediates. We contacted the enzyme expert Dr. Loderer for advice and help with searching for a cascade.
Dr. Loderer provided valuable advice on enzyme cascade complexity and general research. When looking for a suitable cascade we should only consider part of a cascade or just two enzymes, given the complexity of the conditions that specific enzymes require and how different these requirements can be. Therefore, we should also focus on something that has already been produced biologically. Lastly, he told us, that degradation is easier than synthesis.
We implemented Dr. Loderer’s advice by searching for and creating a list of mostly degrading and short enzyme cascades or parts of enzyme cascades with easily verifiable products.
At the start of our project, we were fortunate enough to be approached by Jiayi Alexis Zeng. As a former iGEM team instructor and out of curiosity for our project, she shared her experience with us in some of our weekly discussion meetings, giving us food for thought and new interesting ideas.
Zeng’s interest in biophysics and spider silk as a sturdy, elastic and light material led her to the idea of using condensates to store and produce spider silk in microorganisms. Similarly, spiders also produce their own spider silk in condensate-like structures, after being pushed out of the structure to undergo a transition from a liquid-like to a solid state. Although spider silk is extremely promising as a construction material and for use as naturally degradable bandages or scaffolds for tissue engineering, it is currently difficult to produce artificially due to instability of the silk-producing proteins. If we can improve this, we could benefit several different areas.
We added Zeng’s proposals to our idea list in the early research phase. We further pursued Zeng’s idea by searching for ways to make spider silk production more stable and accessible.
We planned to implement both our condensate and our optogenetics ideas in microorganisms, an area in which Prof. Dr. Mascher is an expert. He has also gained extensive experience as a Principal Investigator (PI) for many previous iGEM teams. We asked him to assist with our project to hear his opinion on the feasibility of our projects within the specified timeframe and scope of iGEM.
Prof. Dr. Mascher’s feedback helped us identify flaws in our ideas and revise them. Regarding our optogenetics idea, we received positive feedback on the two-factor activation of the CAR T-cells by light and by immune-specific recognition to reduce the side effects of CAR T-cell therapy. However, using tumor tissue and E. coli, which can be led to cancerous cells, was simply not feasible in terms of time or within the safety framework set by iGEM for experiments. Although he thought the idea of an enzyme cascade in a condensate was too luck-based to work, Prof. Dr. Mascher liked the idea of using condensates as a sensory system. To avoid being caught off guard by unexpected errors in the experiments, he advised us to make our system more modular, which would ultimately also help us adapt it to other circumstances.
After much discussion and consideration, we decided to focus on developing an RNA sensory system and leave other ideas behind due to their limitations. Following Prof. Dr. Mascher's advice, we then designed a modular RNA sensory system to ensure the success of each experimental step and allow our system to recognize multiple target RNAs. As our project, we landed on detecting an RNA encoding a fluorophore. This serves as a proof-of-principle experiment for our sensory system.
For our sensory system idea, we needed to have a yeast with an inducible fluorescent protein expression. This was necessary firstly to contrast with the fluorescently marked condensate, and secondly to stop the cytosol glowing when the RNA of the corresponding fluorescent protein was bound in the condensates, thereby stopping translation. As Dr. Döring’s research group mostly uses E. coli and yeast in its experiments, we contacted her in hope of gaining insight into yeast transformation and potentially using one of their yeast strains with an integrated fluorescent protein.
Dr. Döring kindly offered us the use of one of their yeast strains with inducible mScarlet genomically integrated, and she also provided us with the mScarlet gene sequence, which was already codon optimized for S. cerevisiae.
After being offered the use of this yeast strain, we researched further whether this fluorescent protein was the right choice for our experiments. Sadly, we ultimately could not accept Dr. Döring’s offer due to the relatively high degradation time of mScarlet, which was not optimal for our system as it did not degrade quickly enough to allow for a fast visual change in cytosolic fluorescent protein expression.
We first sketched out our condensate-based sensory system as a valency-based system, inspired by Michael K. Rosen's work on a similar system, which features a Pumilio factor variant called Pumby as an RNA-binding protein. To further develop our concept, we needed guidance on how to program RNA-dependent sequestration, implement a rapid on/off readout in yeast, and create a practical vector design for reliable yeast transformation and genetic integration. Since Prof. Dr. Alberti, Dr. Franzmann, and Prof. Dr. Honigmann bring deep expertise in biomolecular condensates, yeast-based experimentation and fluorescence microscopy and were familiar with our project, we met with them for a joint expert meeting.
This was a crucial meeting for designing foundational parts of our TRAPS sensory system. As the RNA-binding protein, Prof. Dr. Honigmann proposed replacing the Pumbys with Cas proteins, to make the condensate control sequence programmable and more modular. Later, we discussed switching from a SH3-PRM scaffold designed by Rosen to a toxin-antitoxin system introduced by Heidenreich. This system, featuring toxin and antitoxin Im2 and E9 combined with a tetramerization domain, was successfully tested in the Alberti lab and showed great promise. Because the toxin and antitoxin Im2 and E9 are foreign in yeast, this design could aid reliable condensate formation and add more orthogonality. Additionally, they helped us decide between episomal and genomic integration and optimize our yeast vector design, including the promoter options. Our proof-of-concept idea to target mCherry mRNA was approved because of the RNA's fast degradation time and the option to use GFP as a contrasting tag to our system's tetramerization domain to prove a condensate formed. Lastly, they connected us with other experts in the field for their opinions and help, which was instrumental in advancing our project.
We redesigned fundamental parts of our experiments to test a Cas-based condensate module, in addition to our Pumby-driven system for sensing mCherry mRNA. We continued testing with both concepts, as Cas proteins had several advantages, but the Pumby system’s higher binding affinity to RNA was an interesting factor to test for its role in condensate formation. This unique feature of Pumbys could also potentially allow us to target RNA, which is typically bound to proteins produced by the cell itself and usually can’t be sequestrated. We also switched from Rosen’s scaffolds to Heidenreich’s design, an adaptation which could improve speed and steepness of the switch to condensate formation (responsiveness), orthogonality, and spatial activity restriction (containment). Further, we updated our yeast vector and contacted Dr. Bogdanova and Andrey Pozniakovsky for their expertise and support during yeast transformation.
After deciding to replace the Pumbys with Cas proteins as our RNA binding proteins, as our new idea, we needed help with the experimental design and planning of our new system from an expert in both condensates and Cas proteins. Elsa has intensively experimented with Cas13 proteins and, as a member of the Hyman lab, which researches biomolecular condensates, she has a lot of expertise in both fields.
Firstly, Elsa informed us that Cas9 is primarily employed for genome editing, whereas Cas13 is utilized for RNA-editing, making it the ideal RNA binding protein for our purposes. Secondly, as we didn’t require the RNA-splicing domain (nuclease lobe) of Cas13, she informed us that we could use only the recognition lobe of Cas13 to reduce the size of our vector, or alternatively use a dead Cas13. She also informed us that Cas13 does not use a PAM-sequence, so there is no limitation in binding sites in the RNA. When discussing the ideal experimental implementation of our Cas13-condensate system, we learned from Elsa that we could use dCas13 to target multiple different gRNAs, which would then bind to different parts of the target RNA and connect the scaffold proteins. These guide RNAs will bind to Cas13 at random, resulting in a variety of Cas13 proteins with different gRNAs.
In our Cas13-condensate experiments, we followed Elsa’s advice and used dCas13 to bind the RNA. Prior to this, we used our new insight to search for a suitable binding site of our proteins to our targets and gRNA, free from the restriction of a PAM-sequence.
As we moved from design to execution of our experiments, we needed expert guidance on a robust yeast transformation workflow, vector architecture for simultaneous expression of several components, and tagging strategies that would enable us to reliably quantify protein expression. Dr. Bogdanova and Mr. Pozniakovsky have extensive practical experience with yeast genetics and complex construct design, making them ideal partners to review our plans and discuss potential improvements before we committed to cloning and experiments.
Dr. Bogdanova and Mr. Pozniakovsky reviewed our maps and recommended a multi-cassette layout with individual promoters for each gene, or a polycistronic design with the proteins in order of ascending expression levels to ensure predictable stoichiometry in yeast. Additionally, they suggested that we add antibody tags to monitor expression levels using western blots. For protein purification, they recommended avoiding His-tags and emphasized the importance of codon optimization for yeast to minimize expression variability. We wanted to ensure dynamic condensation rather than aggregation in pulldown assays. For this goal, they advised us to add myc tags at defined positions. The idea to attach Pumby directly to the tetramerization domains, rather than using E9 and Im2 to bridge Pumby to the tetrameric scaffolds originating from Dr. Franzmann, was also approved by them. This should simplify the system and reduce potential cross-interactions. Finally, Dr. Bogdanova and Pozniakovsky shared practical tips for yeast transformation and selection to keep the workflow reproducible and provided a final sequence check before we ordered the plasmids.
Following their advice, we rebuilt our vectors with multiple independent promoters (one per module), introduced myc tags on the relevant components for aggregation monitoring and removed His-tags. We also codon-optimized all ORFs for S. cerevisiae. Conceptually, we implemented the direct fusion of the Pumby to the tetramerization domains and removed the E9 and Im2 linkage from the Pumby-based condensate design. Using their recommendations, we finalized a yeast transformation plan aligned with the new vector architecture and moved forward with experiments, confident that the yeast transformation and correct protein expression could work.
For our experiments in yeast, we needed a build strategy for our constructs which balanced cost, build time, and quality control. This is why we reached out to Nikolett Nagy, Sales Account Manager at GenScript Europe, to assess whether full service gene syntheses and cloning into our vectors would be more effective than our initial plan of ordering fragments and assembling them ourselves.
Nagy advised that, instead of purchasing multiple fragments and performing sequential cloning, GenScript could handle the entire molecular build. This included accepting our plasmid backbones, codon-optimizing and synthesizing the inserts, assembling the multiple inserts, and delivering the sequence-confirmed plasmids. The net result was a lower cost per construct at our target throughput and less bench time without compromizing fidelity.
We adopted the full service build pipeline. We shipped our backbone vectors and annotated maps, specified promoters, terminators and tags, and GenScript returned finished, sequence-verified plasmids ready for yeast transformation. This allowed us to focus on assay development and validation rather than assembly, and, most importantly, the outsourcing proved to be cost-effective given the number and complexity of constructs.
We contacted Dr. Friedrich to pick multiple short Pumby binding sites on mCherry that remain specific at transcriptome scale using our own software.
After we gave Dr. Friedrich a short introduction to TRAPS, she warned us that condensates can misroute mRNAs and that domains near the translation initiation region might suppress translation. She agreed that checking short sites against the genome as a reference would be relatively easy, but checking those short sites against the transcriptome as a reference, which would be harder to implement, would be better to check for real off target effects. Friedrich also showed us a database containing quantitative transcriptome data.
We built our software SEA-STAR to check short sites against the whole transcriptome, score the sequence dissimilarity to the transcriptome using the Boltzmann factor and optionally weighting by gene expression, if gene expression levels are abundant. It ranks individual sites or site sets and reports risk conservatively by taking the strongest or rather worst match per transcript. We also added translation effect assays to our outlook and switched from qualitative to quantitative transcriptome dataset, weighting similarity scores by transcript expression to improve rankings.
We were fortunate enough to meet Richard Golnik on a train by complete chance. We used this chance to discuss secondary structure awareness and its integration into our software to find the perfect binding site of our proteins on the target RNA, with a trained bioinformatician.
Golnik suggested using the software “ViennaRNA” to bring secondary structure awareness into our software, to not only prefer binding sites of proteins on the target RNA that are actually bindable and have little off target effects, but also deprioritize ones buried in hairpin structures. Prototyping a ViennaRNA script and building a Python pipeline around ViennaRNA could help us achieve that goal, he added.
We built our software SEA-STAR to check short sites against the whole transcriptome, score the sequence dissimilarity to the transcriptome using the Boltzmann factor and optionally weighting by gene expression, if gene expression levels are abundant. It ranks individual sites or site sets and reports risk conservatively by taking the strongest or rather worst match per transcript. Because of our talk with Golnik, we considered using ViennaRNA to additionally bring secondary structure awareness into SEA-STAR to make the binding site prediction more applicable and significant.
We contacted Pekárek to have another principled opinion to decide how to or whether to incorporate secondary structure prediction into our design flow and how to optimize finding protein binding sites on target RNA without off target effects.
Pekárek recommended defaulting to 3’UTRs (untranslated regions) targeting when we want minimal perturbation and switching to 5’UTRs or rather the CDS (coding sequence) of the RNA, if translational repression is desired. He cautioned that secondary structure prediction is still unreliable at the resolution we care about. Nevertheless we should avoid tight hairpin structures and prefer open runs as binding sites. Also, where strong conserved or experimentally proved structures exist, they can inform site selection.
We built our software SEA-STAR to check short sites against the whole transcriptome, score the sequence dissimilarity to the transcriptome using the Boltzmann factor and optionally weighting by gene expression, if gene expression levels are abundant. It ranks individual sites or site sets and reports risk conservatively by taking the strongest or rather worst match per transcript. Pekárek helped us decide not integrate the prediction of secondary structure directly, because of the limited development of this field. We still used ViennaRNA to extract the most promising 25 % of mCherry RNA Cas13 binding sites, based on secondary structure. Similarly, we decided against incorporating any sequence function based evaluation as the preferred binding site on the target RNA might highly depend on the scientific question asked. Since users of SEA-STAR, however, can edit the binding site list, preselection via external scores or region restricted searches is straightforward.
The FOSTER workshops provided an ideal opportunity for us to acquire scientific expertise and novel insights on topics such as agile and stress-free project management. The vast majority of students had never previously managed an extensive project. The organization lacked effective strategies for establishing and maintaining an organizational structure in such a large group. The FOSTER workshops provided the necessary information to organize our team and manage the project effectively, thereby ensuring a stress-free environment.
The objective of the workshop on personal stress management was to facilitate the identification of the
origins of stress and the development of strategies for its management. A study was conducted on the
various types of stress present, the factors that were found to be within the scope of influence, and
those that were not. Moreover, a discourse was initiated concerning the factors that were identified as
impediments to the project's progress.
In the workshop on agile project management, the distinctions between classical and agile project
management were examined, and the optimal application of both approaches to our project was deliberated.
This included the organization of the group, the establishment of meeting intervals, the formulation of
interim objectives, the conduction of ongoing evaluations, and the creation of new plans for the
subsequent project phases.
The group structure has undergone an adjustment that has resulted in the formation of specialized working groups addressing specific subjects. These groups are responsible for the dissemination of weekly updates during the primary meeting. Consequently, a corresponding adjustment has been made to our protocol structure with the objective of ensuring a well-ordered documentation process. A lecture on stress recognition was delivered to the entire team, thereby fostering awareness about the issue. Furthermore, a digital repository for emotional distress has been established.
We contacted Simon Doll as an expert for storytelling in scientific presentations. He is a young scientist who is completing his PhD in the field of biomolecular condensates and biophysics of molecules. Mr. Doll has extensive experience in explaining complex research to a wide range of audiences, ranging from non-scientific groups of all ages to specialized scientific communities. He is especially skilled in communicating complex scientific topics in simple words. This strength was recently recognized when he received the “Best Science Slam” award from an expert jury at this year’s CMCB Science Slam, which was held during Dresden Science Night.
Simon advised us to restructure our presentations to convey less information, but put a larger focus on condensate research. This topic is well-known in Dresden, where condensates were first discovered and where a vibrant research network continues to thrive today. However, in other cities, the field is less established, which can make it harder for audiences to grasp.
We included additional information on condensates into our following presentations, to help audience members better understand our complex research topic.
We needed real-world advice on how to present our project across multiple formats, ranging from social media to long-form presentations. This is why we consulted Dr. Magdalena Gonciarz, an expert in storytelling, writing, social media, and visual communication. With several years of experience in both medical communication and working as the PR Officer of an internationally renowned institute, she provided great support.
Dr. Gonciarz reviewed our story for TRAPS and gave valuable feedback to apply the three act structure of setup, conflict, and resolution to our story to make it more memorable. She stressed that while preparing for an event or a presentation, we should always consider the audience and tailor both our content and delivery to what would resonate most and leave a lasting impression. We got the opportunity to present TRAPS to different audiences, ranging from high school students at UniStem Day to seniors during Seniorenakademie as well as a mixed lay audience at the CMCB Science Slam during Dresden Science Night. Lastly, her work on the CMCB’s Instagram account provided an inspiration on how we wanted to run our own account.
Following Dr. Gonciarz’s advice, we restructured our storytelling to feature a clear structure, making it easier to grasp. We told our story to people during three outreach events each targeting a different audience, allowing us to practice various types of presentations. Her work on the CMCB’s Instagram account inspired the approach we took when building our own account, which we launched in May.
We needed comprehensive guidance on scientific storytelling and presentation techniques to effectively communicate our complex research to diverse audiences. Thomas Frei, as Executive Creative Director and co-founder of Cast Pharma, brings extensive expertise in creating medicinal-scientific education materials and programs. Dr. Magdalena Gonciarz, from the CMCB PR Office, is an expert in storytelling, writing, social media, and visual communication with years of experience in medical communication. Together, they provided invaluable insights into crafting compelling scientific narratives that resonate with both scientific and general audiences.
From Thomas Frei and Dr. Gonciarz, we learned the fundamental principles of effective scientific storytelling. They emphasized the critical importance of tailoring presentations to specific target audiences, understanding that what works for a scientific conference may not be effective for public outreach. They taught us strategic word stress techniques to guide audience attention to key information, helping ensure that our most important messages would be remembered. The experts also highlighted the power of strategic pauses in presentations - using silence as a tool to create emphasis, allow for comprehension, and build dramatic tension in our narrative. Additionally, they provided guidance on structuring our story using the classic three-act format of setup, conflict, and resolution to make our research journey more memorable and engaging.
We completely restructured our presentation approach based on their advice. Before each presentation, we now carefully analyze our audience demographics and adjust our content, language complexity, and delivery style accordingly. We practiced implementing strategic word stress patterns to highlight key concepts like "condensates," "RNA detection," and "modularity" in our presentations. We incorporated purposeful pauses at critical moments - after introducing complex concepts, before revealing results, and when transitioning between major sections of our story. We also adopted the three-act narrative structure, presenting TRAPS as a journey from identifying the problem (setup), overcoming experimental challenges (conflict), to achieving our functional RNA sensing system (resolution). These techniques were successfully applied across multiple venues, from technical presentations to lab members to public science communication events.
The Alberti Lab is a renowned research group in the field of condensates. Both Prof. Dr. Alberti and Dr. Franzmann are among the most cited researchers in the world. The lab team draws on extensive hands-on experience in conducting and presenting research projects. Since we ran our experiments in the Alberti Lab and worked together closely with its researchers, we asked them to support us in planning and refining our presentation for the Grand Jamboree in Paris.
From the Alberti Lab’s feedback, we gained valuable insights into how to shape our narrative for presentations. They liked our story and suggested improvements for our presentation, such as reducing technical language and finding simple ways to explain our system. The team advised us on making the presentation more interactive and entertaining, and to cut any unnecessary content. This would make our presentation more engaging and accessible to both scientists and general audiences. In the end, they helped us revise some presentation slides and figures for more clarity. Dr. Franzmann was especially helpful for our team during project management. He supported us in setting a budget for the laboratory work and introduced us to using a digital lab book to keep track of experiments.
After starting our project, we planned our experiments based on the budget suggested by Dr. Franzmann. Each experimental step was carefully recorded in a digital lab book to ensure easy tracking and documentation. We also applied the team’s advice to our presentations by explaining the project as simply and clearly as possible. By practicing in front of audiences with varying backgrounds in the field of condensates, we then continuously reevaluated our approach and refined our storytelling.
We organized an outlook and application discussion with Dr. Jahn to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought his clinical human genetics perspective to evaluate whether our system is practicable for use with patient-derived material and what additional capabilities he would expect in order to employ it in his research. Rather than pursuing further design changes at this stage, we focused on mapping real-world applications, performance requirements, risk profiles and translation pathways within a clinical research context. Our goal was to validate where the concept could deliver the greatest value for his use cases and identify what success criteria an end user like Dr. Jahn would expect in practice.
From the discussion with Dr. Jahn, we gained valuable and constructive criticism on our system. He liked
the modularity of our system and that it operates in vivo. Dr. Jahn envisioned several use cases for our
system. We could make multiple gRNAs target multiple RNAs encoding a certain pathway to investigate
translation factories or even produce them. Another idea was to implement the TRAPS system in the nucleus
of a cell, to target pre-spliced RNA molecules to purify them after condensate formation. He also thought
we could target short-lived or intermediate RNAs, like RNAs containing premature stop codons getting
degraded in the nonsense-mediated decay pathway, possibly shielding them from degradation, which could
help researchers find causes of RNA degradation. Another use case Dr. Jahn could imagine is real-time
visualization of the expression of low-abundant, disease-causing RNA, to further research the mechanisms
of disease formation.
To make our system even more practical, the system could incorporate RNA quantification and sequencing
capabilities and should be inducible or transient.
Guided by Dr. Jahn’s feedback, we included real-time visualization of low-abundance, disease-linked RNAs into the outlook of TRAPS. We will extend the future plans for our system by, aligned with our reversibility plan, operating TRAPS under inducible control to capture rapid expression changes. We appreciated Dr. Jahn’s further suggestions, which have broadened the potential application space and will inform our ongoing prioritization and study design.
We organized an outlook and application discussion with Prof. Dr. Rauner to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought her translational bone biology perspective and her expertise in qPCR as a comparison, to assess its practicability in bone and bone marrow-related contexts and what she would expect for potential use in osteometabolism and osteoimmunology workflows. Rather than seeking further design changes at this stage, we focused on mapping real-world applications, performance requirements, risk profiles and translation pathways in a bone research and clinically adjacent setting. Our goal was to validate where the concept could create the most value for her use cases and what success criteria an end user like Prof. Dr. Rauner would expect in practice.
As Prof. Dr. Rauner frequently uses qPCR in her experiments, she used it to compare our TRAPS system for her use case to quantify RNA. She therefore suggested incorporating a better way to quantify RNA into our system and noted that TRAPS is somewhat more time-consuming than qPCR. At the same time, she appreciated the dynamic sensing that qPCR lacks as well as the modularity of our system, which could help build a translation-centered system that reports or controls translation. Furthermore our system could be useful for her research in studying drug-induced changes in the gene expression profiles of bone cells.
Guided by Prof. Dr. Rauner’s feedback, we included the study on the effect of TRAPS on translation and dynamic drug response profiling in cells to the outlook of our project. We appreciated Prof. Dr. Rauner’s further suggestions, which have broadened the potential application space and will inform our ongoing prioritization and study design.
We organized an outlook and application discussion with Dr. Jahnel to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought his perspective of condensate biophysics to assess responsiveness thresholds, ensure true condensate behavior instead of aggregation and gauge the feasibility of quantitative readouts and further adaptations suitable for lab adoption. Rather than pursuing further design changes at this stage, we focused on mapping real-world applications, performance requirements, risk profiles and translation pathways. Our goal was to validate where the concept could create the most value for his use cases and what success criteria an expert end user like Dr. Jahnel would expect in practice.
Dr. Jahnel encouraged us to incorporate a design to localize sensed RNA or combine both local and global sensing by layering precise micro-perturbations on a mild background to reveal context-dependent behaviors of our condensate system. We discussed titrating interference strength of the target RNA to learn about sequestration thresholds and capacity, buffering and redundancy effects of RBPs and parallel transcripts and the cell’s resilience. Dr. Jahnel then suggested using multiflex targeting to research the cell phenotype alterations, in cases of redundant RNA networks and compensatory routes. For visualization we explored a second color system, by making the two condensate modulus chemically and compositionally orthogonal. Finally to control our system better, he advised building off-switches that could dissolve condensate and let the cellular mechanisms return to their normal state.
In accordance with Dr. Jahnel’s input and our ideas, we included localization assays using bud-localized mRNA of the ASH1 gene versus cytosolic mRNA of the ACT1 gene to test for spatial reporting in our outlook. In the future we also want to perform RNA titration to quantify the detection threshold for condensate formation and test reversibility, switching from galactose to glucose to shut off transcription and monitor condensate disintegration as target RNA declines. We appreciated Dr. Jahnel’s further suggestions, which have expanded the potential application space and will inform our ongoing prioritization and study design.
We organized an outlook and application discussion with Dr. Wurm to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought his perspective in translational oncology and non-coding RNA to assess its practicability with patient-derived bone marrow material, and to understand what he would expect for potential use in ncRNA-guided biomarker and therapy response studies. Rather than pursuing further design changes at this stage, we focused on mapping real-world application, performance requirements, risk profiles and translation pathways in an oncology setting. Our goal was to validate where the concept could deliver the greatest value for his use cases and what success criteria an end user like Dr. Wurm would expect in practice.
The discussion covered topics such as the cellular alterations during condensate formation, which have the potential to disrupt our concept of real-time detection of specific RNA. Additionally, Dr. Wurm proposed the occurrence of condensation within the nucleus that could potentially be applied in visualizing nuclear RNA via staining. The issue of RNA splicing was also discussed, particularly in the context of non-coding RNA. Together we spoke about testing our system in more complex cell types, for which we would need to integrate our Cas protein into the genome. It was confirmed that the system is suitable for cancer-related drug research, emphasizing its application as a high-throughput reporter assay for the detection of specific genes.
Guided by Dr. Wurm’s input, we updated our outlook to prioritize the visualization of low-abundance, disease-linked RNAs, including long non-coding RNAs, which have been proven to play a role in diseases like leukemia. To ensure accurate real-time readouts, we will proceed with our planned translation effect and reversibility assays and we will explore adapting the system to additional model systems beyond yeast. We appreciated Dr. Wurm’s further suggestions, which have broadened the potential application space and will inform our ongoing prioritization and study design.
We organized an outlook and application discussion with the Ader research group to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought their retinal regeneration and iPSC-derived photoreceptor perspective to assess practicability in neuronal and retinal contexts and to understand what they would expect for potential use in retina-focused workflows. Rather than pursuing further design changes at this stage, we focused on mapping real-world applications, performance requirements, risk profiles and translation pathways relevant to neuro-ophthalmology. Our goal was to validate where the concept could deliver the greatest value for their use cases and what success criteria end users like the Ader group would expect in practice.
The meeting with the Ader research group helped us think ahead and develop further strategies to improve and implement TRAPS. They were curious whether we could implement a method for precise RNA quantification and if and how we planned to implement our system into organisms beyond yeast. They suggested that we should try to apply our system in mammalian model organisms and in organoids.
In accordance with the Ader group's feedback and our plan, we strengthened our outlook by adding the implementation in additional organisms, proceeding with our planned zebrafish adaptation as the next step beyond yeast. We appreciated the research group’s further suggestions, which have expanded the potential application space and will inform our ongoing prioritization and study design.
We organized an outlook and application discussion with Prof. Dr. Brand to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought his neuroregeneration and developmental neurobiology perspective to assess practicability and relevance for central nervous system regeneration paradigms and to understand what he would expect for potential use in zebrafish and neural repair workflows. Rather than pursuing further design changes at this stage, we focused on mapping real-world applications, performance requirements, risk profiles and translation pathways in a neurobiology context. Our goal was to validate where the concept could deliver the greatest value for his use cases and what success criteria an end user like Prof. Dr. Brand would expect in practice.
Prof. Dr. Brand advised us to test TRAPS in other organisms and to deliver it via injection rather than reintegrating our system through cloning, as this approach would be easier. He also mentioned concerns about the effort of implementation outweighing improvements in signal-to-noise ratio, and about potential changes in cell physiology caused by our system. Prof. Dr. Brand saw potential in using TRAPS for live monitoring of transcriptional states in embryos and expressed interest in seeing TRAPS implemented in zebrafish to help research nervous system mechanisms controlling regeneration.
Guided by Prof. Dr. Brand’s feedback for our outlook, we prioritized adapting TRAPS beyond yeast, specifically to zebrafish embryos via one-cell microinjection using a codon-optimized, zebrafish-active Cas13. We planned to validate potential physiological impact through assays on translation effects and system reversibility, and added live translational state monitoring during development as an application of TRAPS. We appreciated Prof. Dr. Brand’s further suggestions, which have expanded the potential application space and will inform our ongoing prioritization and study design.
We organized an outlook and application discussion with Prof. Dr. Sterneckert to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought his iPSC and neurodegeneration perspective to assess practicability for human iPSC-derived neurons and glia, compatibility with live cell imaging and what he would expect for potential use in disease modeling workflows. Rather than pursuing further design changes at this stage, we focused on mapping real-world applications, performance requirements, risk profiles and translation pathways. Our goal was to validate where the concept could create the most value for his use cases and what success criteria an end user like Prof. Dr. Sterneckert would expect in practice.
From the discussion with Prof. Dr. Sterneckert, we gained important input to our project. He expressed concerns about our system altering the physiology of a cell and questioned if TRAPS could compete with other RNA sensing ideas, particularly regarding ease of application. Nevertheless he saw potential in the enhanced signal-to-noise ratio our system offers, and would like to see TRAPS integrated with a method to investigate RNA-protein interactions within the cell. He also recommended titrating target RNA to determine the threshold of target RNA that is required for condensate formation.
Analogously to Prof. Dr. Sterneckert’s feedback and our plan for the future of TRAPS, we incorporated RNA titration to define the detection threshold required for condensate formation, as well as translation effect and reversibility assays to assess any physiological impact of TRAPS into our outlook. We also expanded future application examples to include RNA-protein colocalization experiments to probe their interactions. We appreciated Prof. Dr. Sterneckert’s further suggestions, which have expanded the potential application space and will inform our ongoing prioritization and study design.
We were lucky to meet Dr. Zahradník by chance at an iGEM meetup in Prague, after which we organized an outlook and application discussion with him to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We were specifically thankful for his protein engineering and virology perspective to assess practicability for infection model contexts and to understand what he would expect for potential use in virus-host interaction workflows. We focused on mapping real-world applications, performance requirements, risk profiles and translation pathways. Our goal was to validate where the concept could deliver the greatest value for his use cases and what success criteria an end user like Dr. Zahradník would expect in practice.
From the discussions with Dr. Zahradnik, we gained new ideas for real-world applications and input on how to redesign a more stable version of TRAPS. An interesting use case could be to use TRAPS to research cell response during early-stage infection by sequestrating specific mRNAs that are often only transiently expressed during rapid transcriptional changes during a starting viral or bacterial infection. Another specific research topic involving TRAPS could be how coronaviruses manipulate the unfolded protein response (UPR) by uncovering transcriptional changes of UPR genes. Dr. Zahradnik also suggested to use a stabilized version of Cas13 for a future TRAPS design to stop the aggregation of the Cas proteins.
Thanks to Dr. Zahradník’s input, we updated our outlook to include infection-response applications, track early, transient RNA waves during viral or bacterial entry, and to monitor changes in gene expression. We also noted TRAPS’ potential to sequestrate viral RNAs during these assays, thereby preventing virus replication. His feedback also helped us choose a stabilized version of Cas13 to prevent aggregation, since we planned to repeat our experiments for that purpose. We appreciated Dr. Zahradík’s further suggestions, which have expanded the potential application space and will inform our ongoing prioritization and study design.
We organized an outlook and application discussion with Prof. Dr. Hyman to stress-test the use cases of our condensate-based in vivo RNA sensory system in yeast. We specifically sought his condensate and cell biology perspective to assess practicability of TRAPS and its suitability for broad adoption. Rather than pursuing further design changes at this stage, we focused on mapping real-world applications, performance requirements and translation pathways. Our goal was to validate where the concept could create the most value for his use cases and what success criteria an expert end user like Prof. Dr. Hyman would expect in practice.
Prof. Dr. Hyman saw potential in TRAPS as a highly responsive in vivo RNA detection strategy that leverages the unique physics of cellular phase separation. He emphasized that, if TRAPS reliably couples RNA recognition to a switch-like phase transition, it could evolve into a generalizable tool applicable to many research questions.
Guided by Prof. Dr. Hyman’s perspective, we focused our outlook to further enhance TRAPS by planning multiple assays examining translation effects, RNA detection thresholds via titration, localization and reversibility. We appreciated Prof. Dr. Hyman’s feedback which could help establish TRAPS as a generalizable tool.
Inspiration for page layout from: 2024 Heidelberg
From the 23rd to the 25th of May, three of our members Fabi, Basti and Matilda travelled to Frankfurt to attend the BFH (Bielefeld–Frankfurt–Hamburg) Meetup and joined 25 teams and over 150 participants. It was the first large opportunity this year to exchange ideas with other iGEM teams and present our project concept. Over the three days, we joined workshops on topics such as wiki design and pipeline design, and took part in a first project presentation and a poster gallery where we received valuable feedback from both peers and current iGEM judges. As a first deep dive into the community built on curiosity, collaboration and creativity the event gave us a lot of perspectives on our own project. From former iGEM teams that told their journey, to judges and iGEM committee members we recieced alot of advice that changed our project going forward from here. And of course we also had a lot of fun particpating in the sociallizing aspect and want to thank all the people involved in organising it!
On the 5th of July, Fabi, Konrad and Matilda represented our team at the Düsseldorf Meetup. After getting to know the Düsseldorf team in Frankfurt at the BFH, we were invited to join teams for a meetup in Düsseldof. This one-day event was packed with discussions and project presentations, offering a perfect chance to exchange insights at a crucial point in the summer. We shared our progress so far, learned about the other projects and how other teams manage their lab work and enjoyed networking in a welcoming atmosphere. Not only did we gain valuable feedback on our project, but we got the chance to listing to iGEM Ambassador for Europe Florian Hänsel on Human Practices and the Düsseldorfs PI and head of the Institute of Cell and Interaction Biology Prof. Dr. Guido Grossmann, whose presentation gave an fascinating insight into his work. The meetup gave us both inspiration and constructive input that we carried into the next stages of our project. Thanks to the organising team and everyone that we met there It was really fun and we enjoyed not only the talks but the botanical garden and altstadt tour.
On the 9th of August, four of our team members (Doro,Li Jing, Liesa and Paul) took part in the iGEM Global “Pub” Quiz Game, a virtual event hosted by iGEM Lund. The quiz brought together teams from all over the world for a fun and interactive session full of trivia, laughs, and friendly competition. Participating virtually allowed us to connect with fellow iGEMers from diverse countries, test our knowledge about synthetic biology, and enjoy a relaxed, social event in the middle of the busy summer season. The quiz not only offered a great break from lab work, but also strengthened our sense of global community within iGEM. And with us and Prague winning the first place, it was a perfect note to our next planned meetup.
On the 12th and 13th of September, a large group of our members Fabi, Celina, Doro, Malte, Konrad, Dylan, Paul and Lukas joined the Prague Meetup. This international gathering brought together teams from across Central Europe and gave us the opportunity to present our project to a new audience. We enjoyed listening to diverse presentations and taking part in discussions on sustainability and synthetic biology. Beyond the academic programme, exploring the city with fellow participants made this meetup an unforgettable experience.
On the 29th of September, we had the privilege of hosting our own meetup in Dresden. Our entire team welcomed five members of the iGEM Potsdam team, and together we created a day filled with presentations networking opportunities and fun. To strengthen the East German teams and create meetups that are more local, we were eager to create a day to learn and connect. As hosts, we gained valuable organisational experience while ensuring that all participants had the chance to share their progress and challenges. It was exciting to see the lively discussions and the spirit of collaboration in action, and we were proud to contribute to the iGEM community in such a direct way.
On the 17th of October, six of our members Celina, Malte, Franz, Li Jing and Matilda will travel to Eindhoven to take part in the final meetup of the season. This event will be a chance to showcase our almost-finished project and gather valuable last feedback before the Grand Jamboree. We are looking forward to meeting new teams, reconnecting with familiar peeps, and strengthening our network across Europe and maybe eat cheese and enjoy the City of Light.