Team:NUDT CHINA/Implementation
IMPLEMENTATION
Our project presented Cycleblue, a novel tool for controlling cyclin degradation with blue light, therefore controlling cell proliferation. We also presented light inducible PREDATOR (LiPrePro), a novel targeted protein degradation system directly regulated by blue light. LiPrePro is highly modularized, with replaceable features to easily change the targeting module that interacts with the target protein, and the interface where the signal responsive feature can be altered.
As a foundational advance project, our project can potentially be used in wide range of scenarios. Here we list three possible real-world implementations of our design and discussed the possible safety issues and challenges we may have to address.
Possible Working Scenarios, Concerns and Challenges
1. In our opinion, the most reasonable end users of iGEM 2021 project would mainly be scientists working on synthetic biology. Both Cycleblue and LiPrePro can provide new regulatory tools with which cell proliferation or cellular protein abundance can be directly controlled by blue light-responsive protein dimerization. Minimum safety and ethical concerns are raised under such scenario.
2. For scientists working on gene function research, both Cycleblue and LiPrePro can also provide solution on developing novel cellular or animal model to understand the cellular function of specific cell type in a specific time/location. In this scenario, further optimization should be conducted on to reduce the leakiness caused by the background dimerization and improve degradation efficiency. Affection of constitutive or tissue specific system expression in animals should also be evaluated.
3. There is also some possibility that our project might be used for therapeutic purposes. It has been reported Loss of robustness in cell cycle control is related to multiple diseases including cancer, fibrosis, cardiovascular diseases, diabetes, and neurodegenerative diseases. In this case, Cycleblue can be used to control the growth of target cells with high spatial accuracy. Under such scenario, the delivery and expression of Cycleblue system would raise safety concerns especially regarding the specificity of the delivery. Also, huge amount of optimization and trial experiments should have been conducted before the application is pushed this far.
As a methodology study in an exceedingly early stage, we do understand that there will still be countless challenges and setbacks waiting ahead of us. But we do believe that with efforts and love, our project may help making a better world somehow.