Dissertation/Thesis Abstract

Design principles in biological networks
by Goyal, Sidhartha, Ph.D., Princeton University, 2009, 167; 3377995
Abstract (Summary)

Much of biology emerges from networks of interactions. Even in a single bacterium such as Escherichia coli, there are hundreds of coexisting gene and protein networks. Although biological networks are the outcome of evolution, various physical and biological constraints limit their functional capacity. The focus of this thesis is to understand how functional constraints such as optimal growth in mircoorganisms and information flow in signaling pathways shape the metabolic network of bacterium E. coli and the quorum sensing network of marine bacterium Vibrio harveyi, respectively.

Metabolic networks convert basic elemental sources into complex building-blocks eventually leading to cell's growth. Therefore, typically, metabolic pathways are often coupled both by the use of a common substrate and by stoichiometric utilization of their products for cell growth. We showed that such a coupled network with product-feedback inhibition may exhibit limit-cycle oscillations which arise via a Hopf bifurcation. Furthermore, we analyzed several representative metabolic modules and find that, in all cases, simple product-feedback inhibition allows nearly optimal growth, in agreement with the predicted growth-rate by the flux-balance analysis (FBA).

Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum sensing (QS) systems. The QS circuit of V. harveyi integrates and funnels different ecological information through a common phosphorelay cascade to a set of small regulatory RNAs (sRNAs) that enables collective behavior. We analyzed the signaling properties and information flow in the QS circuit, which provides a model for information flow in signaling networks more generally. A comparative study of post-transcriptional and conventional transcriptional regulation suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. Furthermore, we develop a new framework for analyzing signal integration based on Information Theory and use it to analyze quorum sensing in V. harveyi.

Indexing (document details)
Advisor: Wingreen, Ned S.
School: Princeton University
School Location: United States -- New Jersey
Source: DAI-B 70/10, Dissertation Abstracts International
Subjects: Theoretical physics
Keywords: Biological networks, Cell growth, Quorum sensing, Signaling pathways
Publication Number: 3377995
ISBN: 978-1-109-40982-6
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