Spatiotemporal dynamics from interlinked positive-and-negative feedback loops
Abstract/Contents
- Abstract
- Positive and negative feedback loops are two of the most ubiquitous network motifs in biological systems. When a positive feedback loop and a negative feedback loop are coupled together, rich dynamics can emerge. Among these, oscillations in time and space, and pulses of protein activity are some of the commonly observed phenomena in a biological system. In this thesis, we started by computationally study the benefit of a positive feedback in an oscillator, and concluded that oscillators running on interlinked positive-and-negative feedback loops are more robust and tunable in period than the oscillators with only the negative feedback. We then focused on the Xenopus laevis embryonic cell cycle oscillator, a well characterized biochemical oscillator that runs on interlinked positive-and-negative feedback loops. We identified a transition of oscillator topology during Xenopus early development, from the long first cell cycle that depends critically on Wee1/Cdc25 mediated positive feedback, to the short subsequent cell cycles in which the positive feedback is dispensable. Using the human neutrophil-like HL60 cells, we studied the spatiotemporal dynamics of cytoskeleton proteins. We identified a perfect coupling between the protruding front and the retracting rear of a migrating HL60 cells. Myosin exhibits dynamic flashes at the rear of the cell, and the time scale of the flashes depends on local positive and negative feedback loops. When the duration of the myosin flashes is perturbed, the cell exhibits difficulties in turning and has inefficient chemotaxis. We also performed a statistical study comparing the shape and migration dynamics of HL60 cells, and provided evidence of a close correlation between the two phenotypes. Our results showed that the spatiotemporal protein dynamics allowed by proper regulation of interlinked positive-and-negative feedback loops is important in many examples in biology.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Tsai, Tony Yu-Chen |
|---|---|
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
| Primary advisor | Ferrell, James Ellsworth |
| Primary advisor | Theriot, Julie |
| Thesis advisor | Ferrell, James Ellsworth |
| Thesis advisor | Theriot, Julie |
| Thesis advisor | Meyer, Tobias |
| Thesis advisor | Skotheim, Jan, 1977- |
| Thesis advisor | Spudich, James A |
| Advisor | Meyer, Tobias |
| Advisor | Skotheim, Jan, 1977- |
| Advisor | Spudich, James A |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Tony Yu-Chen Tsai. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Ph.D. Stanford University 2013 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Yu-Chen Tsai
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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