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-What is Phoebus?
-Phoebus is the abbreviation of:
-It is a platform that helps users rebuild target proteins into opto-controllable elements, and more than that...
People working in lab always want better tools to control cellular activities quantitively with high spatiotemporal precision and less invasion to cells. Traditional methods were alternated by a precise spatiotemporal approach——Optogenetics. And after years of developing, one of its branches: non-neuronal optogenetics was born. It aims to control various bio-chemical processes in all kinds of cells, not just channel on/off in neural cells. To achieve this goal, researchers need to link opto-switches to target proteins so that the activity of these proteins can be controlled through light.
However, there is no generally standardized protocol on how to design experimental compartments switched by light, and there’s no software to guide users how to ease the process. Therefore, researchers, especially students or freshmen in this field, are facing lots of problems when designing these opto-controllable proteins:
- Which opto-switch protein to use? What is its mode of action? What wavelength does it react to?
- Which linker is appropriate? What is its basic length and solvent accessibility? What is the structure of the fusion protein?
- Do the fusion protein still has normal activity?
Failing to answer these questions may force researchers to focus more on endless DBTL cycles, not on inspiration discovery. So this year, we decided to build an integrated platform that can help and guide users design opto-controllable proteins easier and faster. First, we defined the concept “opto-controllable element”, which is built with three interchangeable parts: opto-switch, target protein, and a linker between them. Simply by changing these parts, we can build any opto-controllable elements that work in different situations, kind of like antibody VDJ rearrangement.
Then, we designed a standardized protocol for opto-controllable elements design: choose a target protein, choose an opto-switch protein, choose the appropriate linker, fusion protein structure prediction, fusion protein activity evaluation and protein sequence optimization.
We then build an opto-controllable element designer module in our platform to perform this process automatically. It is built with five parts: opto-switch protein database,linker database,structure predict algorithm,protein activity evaluator,sequence optimization algorithm.
We also realized that users may require more specific supplementary tools if they are working with a specific situation. For example, if our users want to control cascade reaction rate though light intensity, besides our opto-controllable element designer, we also need an algorithm to calculate the cascade reaction rate. Although tools like this only work in specific situations, they can make our platform much more useful. Since our users may have different kinds of requirements, it is impossible for us to build all these supplementary tools. So, we recommend our users to build open-source tools they find useful by themselves, and combine them with our software. To give examples on how to do this, we build two such tools in our software: one for controlling cascade reaction speed with light, and the other for controlling gene transcription with appropriate opto-controllable transcription factor.
To learn more, check cascade reaction rate control module,transcription control module.
We also want our users to share their ideas and designs of opto-controllable elements. So we decided to build Phoebus Community, a place for sharing and discussing.
To learn more, check Phoebus Community.
We hope that our platform is not limited to what it is since we created it. Instead, it will grow by the effort of our users, it will be more useful, more powerful, and more professional. We hope that it can make non-neuronal optogenetic research and design easier, and researches can focus more on inspiration discovery, not the process of building opto-controllable elements needed to achieve their goals.