Most of the summer, we developed a method of modulating the immune system during cytokine storms for COVID-19 patients. This system is represented in our genetic circuit design:
This genetic circuit was modeled and tested in MATLAB©️’s SimBiology program (Read more on our Model page!). We were able to show a successful negative feedback loop in cytokine modulation. Though this was developed in the context of cytokine storms based on COVID-19, this could be applied to other inflammatory diseases including but not limited to Rheumatoid Arthritis (Bonecchi et al., 2016), Gout (Punzi et al., 2015), Crohn’s Disease (Hazel & O'Connor, 2020), IBD (Bonecchi et al., 2016), and psoriasis (Schuker et al., 2015). We hope future teams will not only investigate our regulatory network in vivo, but also consider its applications to some of the other diseases mentioned.
Cytokine Network and Drug Target Identification:
To further investigate our proposed system’s inflammatory control, we developed a cytokine network model on MATLAB©️’s SimBiology program. This model was built on data of cytokine levels in patients, which was analyzed in previous literature that outlined relationships among key cytokines (Yiu et al., 2012).
Not only was this cytokine network useful to observe the cytokine storms and have relevant inputs to our systems, but this also gave us the opportunity to target different cytokines with our system. Using this cytokine network, we were able to identify the optimal target of our single chain variable fragment to reduce the cytokine storm in COVID-19 patients as effectively as possible. We found IL-1 to be the most effective target for our system.
While the majority of our work was focused on the design of a mechanism of immunomodulation, we did end up designing a few parts that would be used in our genetic circuit. Though these parts weren’t characterized, we hope other teams will use our proposed designs to implement and validate our proposed system. We created basic parts of the individual endoribonuclease necessary for gene regulation. Next, we implemented these in our system along with specific cytokine promoters to create our AND gate design. To see how our parts were used in our design see the diagram below or the parts page.