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The Effect of Noisy Protein Expression on E. coli/Phage Dynamics

Chapman-McQuiston, Emily Louise (2008) The Effect of Noisy Protein Expression on E. coli/Phage Dynamics. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    It has long been suspected that population heterogeneity, either at a genetic level or at a protein level, can improve the fitness of an organism under a variety of environmental stresses. However, quantitative measurements to substantiate such a hypothesis turn out to be rather difficult and have rarely been performed. We examine the response of Escherichia coli (E. coli) to infection by viruses known as phage. In order to inject its DNA into a bacterium, the phage must first bind to a specific receptor protein and consequently the number of receptors per bacterium is related to the bacterial susceptibility to infection. Like many proteins in a bacterial population, the number of expressed receptor proteins in an individual cell is not deterministic but stochastic. In this project, experiments and model calculations are used to study how the noisy expression of phage receptors in a bacterial population changes the short-time population dynamics of an isolated and well-mixed E. coli/phage system. We find that when phage are present in the system, the selective killing of bacteria expressing high numbers of phage receptors creates a phenotype selection and the bacterial population can no longer be considered as having a homogeneous susceptibility to the phage pressure. It is shown that a heterogeneous bacterial population is significantly more fit compared to a homogeneous population when confronting a phage attack. We find that a small percentage of cells which are expressing few phage receptors become important because these bacteria persist despite the presence of phage. In view of their important roles in environmental adaptation, in various diseases and potentially in evolution, a fundamental understanding of this minority of cells remains a significant challenge.


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    Item Type: University of Pittsburgh ETD
    ETD Committee:
    ETD Committee TypeCommittee MemberEmail
    Committee ChairWu, Xiao-lunxlwu@pitt.edu
    Committee MemberSwigon, Davidswigon@pitt.edu
    Committee MemberCoalson, Robertrob@mercury.chem.pitt.edu
    Committee MemberDuda, Robertduda@pitt.edu
    Committee MemberSavinov, Vladimirvps3@pitt.edu
    Title: The Effect of Noisy Protein Expression on E. coli/Phage Dynamics
    Status: Unpublished
    Abstract: It has long been suspected that population heterogeneity, either at a genetic level or at a protein level, can improve the fitness of an organism under a variety of environmental stresses. However, quantitative measurements to substantiate such a hypothesis turn out to be rather difficult and have rarely been performed. We examine the response of Escherichia coli (E. coli) to infection by viruses known as phage. In order to inject its DNA into a bacterium, the phage must first bind to a specific receptor protein and consequently the number of receptors per bacterium is related to the bacterial susceptibility to infection. Like many proteins in a bacterial population, the number of expressed receptor proteins in an individual cell is not deterministic but stochastic. In this project, experiments and model calculations are used to study how the noisy expression of phage receptors in a bacterial population changes the short-time population dynamics of an isolated and well-mixed E. coli/phage system. We find that when phage are present in the system, the selective killing of bacteria expressing high numbers of phage receptors creates a phenotype selection and the bacterial population can no longer be considered as having a homogeneous susceptibility to the phage pressure. It is shown that a heterogeneous bacterial population is significantly more fit compared to a homogeneous population when confronting a phage attack. We find that a small percentage of cells which are expressing few phage receptors become important because these bacteria persist despite the presence of phage. In view of their important roles in environmental adaptation, in various diseases and potentially in evolution, a fundamental understanding of this minority of cells remains a significant challenge.
    Date: 23 January 2008
    Date Type: Completion
    Defense Date: 13 November 2007
    Approval Date: 23 January 2008
    Submission Date: 15 October 2007
    Access Restriction: No restriction; Release the ETD for access worldwide immediately.
    Patent pending: No
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    URN: etd-10152007-153219
    Uncontrolled Keywords: flow cytometry; stochastic protein expression; bacteria; phage
    Schools and Programs: Dietrich School of Arts and Sciences > Physics
    Date Deposited: 10 Nov 2011 15:03
    Last Modified: 07 May 2012 14:42
    Other ID: http://etd.library.pitt.edu/ETD/available/etd-10152007-153219/, etd-10152007-153219

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