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Title:Studying the role of noise in E. coli chemotaxis
Author(s):Bano, Roshni
Director of Research:Chemla, Yann R
Doctoral Committee Chair(s):Chemla, Yann R
Doctoral Committee Member(s):Kuehn, Seppe; Rao, Christopher V; Gruebele, Martin
Department / Program:School of Molecular & Cell Bio
Discipline:Biophysics & Quant Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Noise
chemotaxis
Abstract:Biochemical signaling networks allow living cells to adapt to changing environments, but these networks have to cope with unavoidable number fluctuations (“noise”) in their molecular constituents. These fluctuations can arise over time in an individual cell (due to inherent stochasticity in chemical reactions) or manifest themselves as differences between individual cells. The chemotaxis signaling network of Escherichia coli, using which these bacteria modulate their random walk-like run/tumble swimming pattern to navigate their environment, is a paradigm for the role of noise in cell signaling. The E. coli chemotaxis network thus has been my model system of choice to characterize and study the role of these different types of noise. A key signaling protein in this network, CheY, when activated by phosphorylation, causes a switch in the rotational direction of the flagellar motors propelling the cell, leading to tumbling. Since the degree of CheY activation/phosphorylation is a function of the cell’s environment, the CheY-P concentration, [CheY-P], is a measure of the output of the chemotaxis network and random fluctuations in [CheY-P] in time provide a proxy for network noise. However, measuring these fluctuations in the single cell, especially at the relevant timescale of individual run and tumble “decision making” events, remains a challenge. In my thesis work, we developed an approach to quantify short timescale (0.5-5 s) network noise due to [CheY-P] fluctuations using rotational switching statistics of individual flagella observed using time-resolved fluorescence microscopy of individual optically trapped E. coli cells. This work revealed the existence of high network noise at steady state which may be critical to driving cell tumbling. Upon activation of the network, this noise is reduced dramatically; we connect this reduction, through modeling, to the existence of an intrinsic kinetic ceiling on network activation, which may be functionally important to prevent unproductive tumbling. In collaboration with the research groups of Seppe Kuehn, Ido Golding and Nigel Goldenfeld, using single-cell optical trapping, I also studied evolution in E. coli motility/chemotaxis and the cell-cell variation therein in strains that were selected for faster collective migration through agar. In this work, we attempt to connect changes in relevant molecular constituents of the chemotaxis network, CheR and CheB, to changes in motility and chemotaxis at the individual and population level.
Issue Date:2020-12-03
Type:Thesis
URI:http://hdl.handle.net/2142/109604
Rights Information:Copyright 2020 Roshni Bano
Date Available in IDEALS:2021-03-05
Date Deposited:2020-12


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