Team:Lund/Implementation
Introduction
During the project, the focus has been distributed on different areas to explore the project's future potential in the bigger picture. Team Lund proposes a three-angle-focused implementation; the lab, entrepreneurial and modeling angle.
The Lab Angle
After more extensive testing of what works best, our proposed implementation would be a probiotic such as L. reuteri, B. subtilis, or E. coli nissle. If we were to make a finished product, we would select the most effective inhibitors and combine them to get the best curli inhibitory effect. We would integrate the gene encoding for the inhibitors into the genome of our chosen bacteria and make sure it expressed them adequately. We might change our construct by fusing our larger proteins with our curli inhibiting peptides, and a linker in between was easily cut apart by enzymes found in the small intestine. A kill switch could also be introduced to decrease the unintentional spreading of the bacteria outside of the body. A probiotic capable of expressing and secreting effective inhibitors would be the ultimate goal of a subsequent project building on the results of our projects. If this could be achieved in the lab, that probiotic would eventually be introduced to the market after necessary approval.
The Entrepreneurial Angle
Human practices have contributed vastly to the proposed implementation of our project. The input from Zack Abbot, CEO of ZBiotics, the results of our survey, and Jordi Riera from AB-Biotics have been of great help.
The discussion with Zack Abbot helped us understand the importance of playing it simple and cooperating with the consumers' habits. Earlier in the project, we had ideas on making our proposed product into a smoothie or another form of a food product. However, after talking to Zack Abbot, we understood that it is easier to get consumers to regularly take a pill since it is easy to add to a morning routine, especially if the people are already taking a daily supplement.
When our survey results were analyzed, this also supported Zack Abbot's remark. One of the primary, uniform reasons why people were not taking probiotics was habitual. Although we also got an answer that most people prefer to take probiotics in the form of food than pills (84% compared to 44%), we decided to prioritize habits. We concluded that our proposed product should be a pill that one can take daily. Another person that helped confirm this conclusion was Jordi Riera of AB-Biotics. AB-Biotics is a highly successful company on the probiotic market in Spain that produces pills and capsules designed for oral administration. This confirmed that a pill or capsule is a good idea for a proposed final product and that consumers are used to that form of supplement or medicine.
A hurdle that prevents us from introducing an engineered probiotic to the market in the EU is the current GMO (Gene Modified Organism) legislation. As of 2021, a potential alternative market to the EU is the US, with its more relaxed legislation regarding GMOs. Team Lund acknowledges that the safety aspect is crucial. It is not just a matter of political lobbying to introduce our future GM bacteria on the European market. Our bacteria must be safe to consume and not harm human health nor the environment. With this in mind, we would like to stress that our proposed commercial implementation is far off into the future, with plenty of research and legislation changes required.
In conclusion, team Lund proposes that our engineered probiotics, if put on the medical market that allows GM bacteria in the future, should be a pill or a capsule as a product. Our end users would most likely be people with a family history of Alzheimer's or other neurodegenerative diseases.
Modelling
The Cure-li model plays a vital role in the implementation of probiotic treatment. It forms the bridge between in-vitro and in-vivo studies. Using the model, we can derive essential metrics such as the required probiotic bacteria concentration in the gut, how close the probiotic bacteria need to come to the curli fibrils, and whether the probiotic needs to colonize the gut or if it can simply pass through it. These metrics would then be used to optimize the delivery of the probiotic bacteria and set requirements on the fitness of the bacteria, hence reducing the number of experiments needed to move from in-vitro to in-vivo.