Synthetic optobiology : engineering of photodissociable proteins and application to optical control of biology
Abstract/Contents
- Abstract
- If protein activities can be controlled with light, the exquisite spatial and temporal control possible would enable more precise understanding of how proteins function within signaling pathways and control cell behaviors. Previously described approaches either relied on protein relocalization to indirectly regulate protein activity, or required extensive screening and optimization. Thus, these methods have been successfully used to control only a few proteins, and a generalizable way to control protein activities has not yet been achieved. We describe the discovery and engineering of the first synthetic light-controlled protein-protein interaction, and the use of this interaction to develop a generalizable design for constructing light-inducible proteins. We used this design, termed "Fluorescent Light-inducible Proteins", or "FLiPs", to successfully control four protein classes with light: guanine nucleotide exchange factor, protease, kinase and Cas9. Using our engineered light-controllable kinases, we discovered a previously undetected feedback mechanism in the Raf-MEK-ERK cascade, demonstrated the potential of photoswitchable kinases in drug development, and proved the efficacy of these light-controllable domains in vivo. Our results demonstrate that engineered photodissociable proteins enable a general method for spatiotemporal investigation of protein function in cells and animals.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Zhou, Xin |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Lin, Michael Z |
| Thesis advisor | Lin, Michael Z |
| Thesis advisor | Cui, Bianxiao |
| Thesis advisor | Huang, Kerwyn Casey, 1979- |
| Advisor | Cui, Bianxiao |
| Advisor | Huang, Kerwyn Casey, 1979- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Xin Zhou. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Xin Zhou
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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