Measuring and Modeling The Response Characteristics Of The Environmental Phosphate Transducer In Escherichia Coli

<p>The PhoR/PhoB two-component system in <em>Escherichia coli</em> is a biological transducer that senses the limitation of environmental inorganic orthophosphate, the bacteria's preferred source of the essential nutrient phosphate, and transmits that information to the interior of the cell initiating a response that mitigates phosphate starvation. In the first part of this study, we present and apply a fluorescence microscopy technique to measure, <em>in vivo</em>, the dynamic response characteristics of the transducer with single-cell resolution. We report that the transience in the PhoR/PhoB TCS response is consistent with the transducer having a threshold sensitivity to the concentration of environmental phosphate, below which the transducer stochastically switches from a low to high operating point. Significantly, we find that the transducer response overshoots before settling to its final operating point. In the second part of this study, we investigate a series of minimal models, simple extensions of the birth-death process, that have response characteristics in common with the measured transducer response. We find that using the Hill equation as the functional form of the birth rate in an autoregulating birth-death process gives a bistable system with stochastic switching. This demonstrates that the model complexity necessary to reproduce the transducer's qualitative behavior is less than the complexity of the biological system.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physics

Year

2013

Author dc:creator

• Sood, Chetan

Contributors dc:contributor

• Ken P. Ritchie
• Brian Todd
• Ephraim Fischbach
• Barry L. Wanner

• bistability
• overshoot
• single-cell fluorescence microscopy
• stochasticity
• transience
• two-component system
• Biophysics
• Cell Biology

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/43

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-1173