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The roles of intergeneration inheritance and intrageneration molecular dynamics in shaping living cells

Vashistha, Harsh (2021) The roles of intergeneration inheritance and intrageneration molecular dynamics in shaping living cells. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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We study two important dynamical processes in the bacterium E. coli. The first focuses on understanding how the inheritance of non-genetic components influences cellular properties and restrict heterogeneity in future generations. Heterogeneity in physical and functional characteristics of cells proliferates within an isogenic population due to stochasticity in intracellular biochemical processes and in the distribution of resources during divisions. Conversely, it is limited in part by the inheritance of cellular components between consecutive generations. The aim of this study is to characterize the dynamics of non-genetic inheritance in the simple model organism E. coli, and how it contributes to restraining the variability of various cellular properties. We describe the design of a novel microfluidic device that can trap sister cells in the same environment for 10s of generations. We introduce a new method for measuring proliferation of heterogeneity in bacterial cell characteristics, based on measuring how two sister cells become different from each other over time. Our measurements provide the inheritance dynamics of different cellular properties, and the ‘inertia’ of cells to maintain these properties along time. We find that inheritance dynamics are property specific and can exhibit long-term memory (∼10 generations) that works to restrain variation among cells. Our results can reveal mechanisms of non-genetic inheritance in bacteria and help understand how cells control their properties and heterogeneity within isogenic cell populations. In the second study, we turn our attention to the specific question of cell size control in bacteria and focus on the role of the Min proteins dynamics in determining cell size. We demonstrate that the Min proteins, known to exhibit pole-to-pole oscillation responsible for localizing the septal ring to mid-cell in E. coli, play a crucial role in setting the cell size. We show that manipulating the concentrations ratio of the Min proteins in the cell destabilizes their oscillation temporarily and leads to a delay in the formation of the division ring until the cell reaches a size that would stabilize the oscillation again. As a result, cells divide at a new stable size which is longer than observed in earlier cell-cycles with the preceding concentrations.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Vashistha, Harshhav17@pitt.eduhav17
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSalman, Hannahsalman@pitt.eduhsalman
Committee MemberWu, Xiao-Lunxlwu@pitt.eduxlwu
Committee MemberPekker, Davidpekkerd@pitt.edupekkerd
Committee MemberSavinov, Vladimirvladimirsavinov@pitt.eduvladimirsavinov
Committee MemberLee, Robinrobinlee@pitt.edurobinlee
Date: 8 October 2021
Date Type: Publication
Defense Date: 29 July 2021
Approval Date: 8 October 2021
Submission Date: 5 August 2021
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 130
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Physics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Biophysics, Cell growth, Microfluidics, Cell size, Inheritance
Date Deposited: 08 Oct 2021 19:54
Last Modified: 08 Oct 2022 05:15


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