Systems of chemical reactions in biology : dynamics, stochasticity, spatial effects and model reduction
Name
261504255-MIT.pdf
Description
Full printable version
Size
8.31 MB
Format
Adobe PDF
Checksum (MD5)
6f7bc5b505ac72f2a59128836ba57a2c
Author(s)
Gómez Uribe, Carlos Alberto
Advisor(s)
George C. Verghese and Leonid Mirny.
Date Issued
2008
Publisher
Massachusetts Institute of Technology
Abstract
Cells are continuously sensing and processing information from their environments and responding to it in sensible ways. The communication networks on which such information is handled often consist of systems of chemical reactions, such as signaling pathways or metabolic networks. This thesis studies the dynamics of systems of chemical reactions in the context of biological cells. The first part of this thesis analyzes the osmo-regulation network in yeast, responsible for the regulation of internal osmolarity. We measure the system's step response in single cells, and find that the steady state is independent of the input, a property termed perfect adaptation that relies on integral feedback control. We then consider the signaling cycle, a pattern of chemical reactions that is often present in signaling pathways, in which a protein can be either active (e.g., phosphorylated) or inactive (e.g., unphosphorylated). We identify new regimes of static and dynamic operation, and find that these cycles can be tuned to transmit or digitize time-varying signals, while filtering input noise. The second part of this thesis considers systems of chemical reactions where stochastic effects are relevant, and simplifies the standard models. We develop an approximate model for the time-evolution of the average concentrations and their variances and covariances in systems with and without spatial gradients. We also describe a framework to identify and derive approximate models for variables that evolve at different time scales in systems without spatial gradients. These tools can help study the impact of stochastic and spatial effects on system behavior.
Description
Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 221-232).
Subjects
Harvard University--MIT Division of Health Sciences and Technology.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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