THESIS
2012
xii, 128 p. : ill. (some col.) ; 30 cm
Abstract
Genetic oscillators that arrive from the dynamic interaction of molecular components have been shown to associate with the regulation of cell cycle, tissue compartmentalization, circadian rhythms and responses of several signaling pathways. Unveiling the functional properties of such oscillators becomes crucial for the understanding of these cellular processes and for the characterization of fundamental properties of more complex clocks. Adapting a reverse engineering approach, I showed how the dynamics of minimal two-component oscillator were drastically affected by its genetic implementation. Our synthetic oscillators are composed of two components, activator and repressor, where the activator and repressor can respectively activate and inhibit their expression and that of the othe...[
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Genetic oscillators that arrive from the dynamic interaction of molecular components have been shown to associate with the regulation of cell cycle, tissue compartmentalization, circadian rhythms and responses of several signaling pathways. Unveiling the functional properties of such oscillators becomes crucial for the understanding of these cellular processes and for the characterization of fundamental properties of more complex clocks. Adapting a reverse engineering approach, I showed how the dynamics of minimal two-component oscillator were drastically affected by its genetic implementation. Our synthetic oscillators are composed of two components, activator and repressor, where the activator and repressor can respectively activate and inhibit their expression and that of the other in the transcriptional level. Employment of different modular components resulted in functional and non-functional oscillators. In the case of functional oscillators, 17% or 27% of cells after the transfection of the circuits demonstrated fluorescent oscillations in the period of 150-200 minutes. In addition to the oscillator construction, I attempted to couple the oscillations between two homogenous cells. I designed modules that will be important for future synchronization use. Mathematical modeling of our oscillator design successfully demonstrated the possibility of oscillation in the period of 150 minutes which is consistent with our experimental results. Together, they provided an important foundation for the understanding of biological clocks.
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