Team:NUDT CHINA/Model/Discussion
Designed Protein Degradation Method Based on
Trim21 And Nanobody
Discussion
Future Work
From the previous analysis, it can be seen that the idea based on increasing the concentration of the input plasmid by increasing the rate of protein degradation or reduce the concentration of protein is limited by the intracellular XXX , and increasing plasmid dosage also has a non-negligible limiting effect on cell growth and proliferation. Therefore, we hope to explore how to complete the entire circuit through modeling, and improve the threshold of the reaction speed from the underlying improved circuit. When the original constructed plasmid is expressed, the translated trim21 and the antibody peptide chain are cleaved by the p2a method, and the function of trim21-mediated ubiquitination functions after the antibody-antigen complex (Fig.). However, if the antibody and trim21 are directly linked after expression by designing the gene sequence, which means that trim21 is also attached to the complex (Fig.).Therefore, Trim21 can directly initiate the ubiquitination of the antigen-antibody complex.(It is reflected in the equation of the model to skip the S + E3 <-> SE3 link) . Through computer simulation (Fig.), we evaluate the effect of this improvement and compare it with the original design,finding that (Fig.)
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Our modeling and analysis was focused to achieve a better theoretical grounding of the relation between plasmid dosage and protein degradation rate. By integrating our model with data analysis from the experimental data we collected, we were able to provide design considerations for future iGEM team who will build upon our work, building circuits that rely on our minds.In addition，the analysis of different influencing factors also makes us think more deeply about experimental improvement and future clinical application, and can provide more feasible opinions.
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| name | city | |
|---|---|---|
| Tanmay | Bangalore | 560001 |
| Sachin | Mumbai | 400003 |
| Uma | Pune | 411027 |
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