Partnership
TU-Eindhoven
The superb partnership between our team and the team TU-Eindhoven started end of May. From the start onward both teams were determined to tackle the partnership criteria. This was improved by setting up a shared slack, drive, and WhatsApp group for communication and sharing of information. Moreover, meetings were set up to be held at least every two weeks, increasing over time within the areas of collaboration.
The collaboration consisted of four major parts.
Firstly, human practices were the most obvious point of overlap, as TU-Eindhoven is working on a diagnostic tool for inflammatory bowel disease (IBD) and since IBD patients are three times more likely than the general population to have irritable bowel syndrome (IBS). The second and third collaboration parts were the exchange of information, tips and tricks shared between the respective Lab and Modeling teams. Lastly, our two teams (TU-Eindhoven and us) agreed to help each other out with the documentation. On the one hand the team from Eindhoven gave us insight into their organization and how they keep track of what needs to be done and on the other hand both teams agreed to share wiki texts to make sure the texts are understandable and well written.
The project of iGEM TU-Eindhoven 2021(see also their wiki)
Non-Invasive Monitoring of IBD using Genetically Engineered Bacteria as Living Sensors Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the intestine. Globally over 6 million people suffer from IBD, and this number keeps rising. The current monitoring procedure for this disease lacks specificity, resulting in unnecessary follow-up examinations that are invasive, expensive, and time-consuming, which calls for an alternative procedure.
Our solution - IBDetection - consists of a pill that can be ingested orally by the patient and delivers living, safe, genetically engineered Escherichia coli BL21(DE3) to the intestine. These bacteria include a biorthogonal sensing cascade to detect tetrathionate - an inflammation biomarker - with high specificity, and in turn activates translation of acoustic reporter genes, resulting in the formation of gas vesicles in the bacteria. These gas vesicles can then be measured outside of the body using conventional ultrasound equipment. This method provides a cost-effective, easy-to-use solution to rule out unnecessary follow-up examinations in a specific and non-invasive manner using fast imaging methods.
Human Practices
Discussions & sharing of progress
The members of each Human Practice team met every two weeks to discuss the progress, especially in the areas we collaborated with, for example the survey and the interviews. We also talked about topics like informed consent and presentation of our project. This outside point of few given by the other team, respectively, was especially helpful to work out the respective problems, challenges, and points we missed to improve our project.
Survey
The survey we prepared for the society provided a great opportunity to collaborate with our partner team in a way in which both teams had great benefits from the collaboration. Firstly, we dedicated one chapter of our survey to questions about IBD which were designed by the iGEM team TU-Eindhoven before we included them into our survey. Secondly, both teams mutually reviewed the survey questions before publishing the survey to confirm the understandability as well as that the questions are as unbiased as possible. Furthermore, the survey was kindly translated into Dutch by the iGEM team TU-Eindhoven and distributed in the Netherlands in order to reach more people with our survey.
Patient Interviews
This part of our collaboration started early during a meeting, where we discussed our general plan with human practices and what ideas we had to get into contact patients and how to receive information. During this talk the team TU-Eindhoven saw our point of going for zoom interviews and in the end also decided to lay beside their initial idea of doing a patient survey for one-on-one interviews, to better understand the patient perspective. Being the ones going into the patients perspective on the project ideas, the most important questions for the respective teams were exchanged to include them into the surveys and into the interviews. This increased the sample size and input of ideas and suggestions for both teams. Furthermore, our team found a patient with IBD who was interviewed by us for the iGEM team TU-Eindhoven.
Ethics/Safety
Due to the shared safety and ethics concerns related to the topic of GMO’s in either the possible medicine or diagnose tool, we organized a meeting with an ethics Professor for the team TU-Eindhoven to join. To prepare the meeting, questions were collected, discussed, and also feedback was given by both teams. The meeting was held together giving both teams the chance to get an insight in the other team's thoughts and problems, resulting in a better understanding of the matter. Prof. Dr. Rath was gave us more insight into the ethical and safety considerations of our projects as well as an idea of what would be necessary if we would like to further develop our ideas into the direction of a medication or diagnose tool.
Informed consent
Since both teams in the end decided on doing patient interviews and were talking a lot to specialists, we made the team from TU-Eindhoven aware that an informed consent is needed from both groups to be finally allowed to present the acquired knowledge on our wikis.
Moreover, our informed consent also made sure that those participating where aware of the fact that both of our projects are most likely not going to result in a final product available for them.
Lab
Discussions & sharing of progress
During the many discussions and progress updates done between the lab teams a lot of smaller problems were able to be solved and avoided, also giving each other tips like the usage of an online tool to determine protein degradation rates, which we were happy to introduce to our partner.
Moreover, it was planned to collaborate on the usage of the gut-on-a-chip system for testing also for the team from TU-Eindhoven, which in the end was not possible due to shipping and expenses.
Troubleshooting
After half of our lab time had passed, it was time to discuss some difficulties and obstacles we faced in the lab with a greater number of bright minds to continue making progress with our lab work. Therefore, our lab team organized a troubleshooting meeting together with our partner team from Eindhoven, as well as overall five supervisors from both teams. In this meeting, both teams presented their progress in the lab before discussing the difficulties and open questions that our teams were facing in the lab. The lab team from the TU Eindhoven was able to get input on the optimal concentration of doxycline to use in their experiments, as well as suggestions on how to optimize their sequencing results for large plasmids. For our lab team, it was really helpful to get more Know-How on the use of Ampicillin as a selection pressure for our GMOs as well perform troubleshooting on the expression of our enzymes in lactobacilli. This troubleshooting meeting was very valuable and helped us in our further progress of our laboratory work. Thereby, we want to thank our partner Team from the TU Eindhoven with their supervisors Prof.dr.ir. Luc Brunsveld, Prof. Dr. Maarten Merkx as well as our supervisors Dipl.-Ing. Dr. Hans Marx, Dipl.-Biol. Dr.sc. Martin Altvater and Dipl.-Ing. Dr. Hannes Russmayer for the great troubleshooting meeting!
Biosafety
We offered that the team from Eindhoven could feature our capsule as another example of how it could be used, since our system is versatile, can be applied for different approaches and helps with biosafety as well as mucoadhesion.
This was possible since both approaches have living GMOs, which should settle in the intestine and profit from the longer residue time. We therefore went forward by sharing our design, system and work knowledge with them also holding a meeting for this purpose.
Modelling
Discussions & sharing of progress
We met our modeling collaboration partner Eindhoven on a regular basis to give short progress reports and discuss issues with the models. To ensure compatibility and easier communication our team decided to use the same software as Eindhoven and our partners kindly shared introduction videos with us. The regular exchange helped us in resolving issues with SimBiology and gave us new ideas on how to proceed with our model.
Tips & Tricks instruction guide to using SimBiology
As both of our teams encountered similar problems and errors, we decided to create a tips & tricks sheet to help future iGEMers with their modeling in SimBiology. On the sheet, we included important things to consider prior to creating the model, frequently occurring issues while building the model and tips for simulating and analyzing the data.
Other Collaboration points
- Furthermore, both teams took part in collaborations set up by the other team. The team of TU-Eindhoven therefore sent us a recipe for our cookbook, and we created a lesson plan for their elementary school program.
- We also created some shared content on our social media websites and promoted each other's work.
- Both teams also agreed to help each other with their respective wiki content. If one team was unsure about the clarity and content of their documentation the other teams was there to help out and to give an unbiased opinion.