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Title:Multiscale modeling of microbial communities
Author(s):Blanchard, Andrew Edward
Director of Research:Lu, Ting
Doctoral Committee Chair(s):Tajkhorshid, Emad
Doctoral Committee Member(s):Kuhlman, Thomas; Cooper, Lance
Department / Program:Physics
Discipline:Physics
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Microbial Communities
Social Interactions
Population Structures
Abstract:Although bacteria are single-celled organisms, they exist in nature primarily in the form of complex communities, participating in a vast array of social interactions through regulatory gene networks. The social interactions between individual cells drive the emergence of community structures, resulting in an intricate relationship across multiple spatiotemporal scales. Here, I present my work towards developing and applying the tools necessary to model the complex dynamics of bacterial communities. In Chapter 2, I utilize a reaction–diffusion model to determine the population dynamics for a population with two species. One species (CDI+) utilizes contact dependent inhibition to kill the other sensitive species (CDI-). The competition can produce diverse patterns, including extinction, coexistence, and localized aggregation. The emergence, relative abundance, and characteristic features of these patterns are collectively determined by the competitive benefit of CDI and its growth disadvantage for a given rate of population diffusion. The results provide a systematic and statistical view of CDI-based bacterial population competition, expanding the spectrum of our knowledge about CDI systems and possibly facilitating new experimental tests for a deeper understanding of bacterial interactions. In the following chapter, I present a systematic computational survey on the relationship between social interaction types and population structures for two-species communities by developing and utilizing a hybrid computational framework that combines discrete element techniques with reaction-diffusion equations. The impact of deleterious and beneficial interactions on the community are quantified. Deleterious interactions generate an increased variance in relative abundance, a drastic decrease in surviving lineages, and a rough expanding front. In contrast, beneficial interactions contribute to a reduced variance in relative abundance, an enhancement in lineage number, and a smooth expanding front. More specifically, mutualism promotes spatial homogeneity and population robustness while competition increases spatial segregation and population fluctuations. To examine the generality of these findings, a large set of initial conditions with varying density and species abundance was tested and analyzed. The results and the computational framework presented provide the basis for further explorations of individual based simulations of bacterial communities. For Chapter 4, I consider the role of gene regulation in shaping the outcome of competition between a bacteriocin (i.e. toxin) producing and sensitive strain. In natural systems, bacteriocin production is often conditional, governed by underlying quorum sensing regulatory circuitry. By developing an ordinary differential equation (ODE) model integrating population dynamics with molecular regulation, we find that the ecological contribution of bacteriocin production can be positive or negative, determined by the tradeoff between the benefit of bacteriocins in mediating competition and the fitness cost due to metabolic load. Interestingly, under the naturally occurring scenario where bacteriocin production has a high cost, density-dependent synthesis is more advantageous than constitutive synthesis, which offers a quantitative interpretation for the wide prevalence of density-related bacteriocin production in nature. By incorporating the modeling framework presented in Chapter 3, the results of the ODE model were extended to the spatial setting, providing ecological insights into the costs and benefits of bacteriocin synthesis in competitive environments. For the final research chapter, I consider the impact of growth coupling on protein production at both the single cell and population scales. The same machinery (e.g. ribosomes) and resources (e.g. amino acids and ATP) are used within cells to produce both endogenous (host) and exogenous (circuit) proteins. Thus, the introduction of a gene circuit generates a metabolic burden on the cell which can slow its growth rate relative to the wild type. Building off of the computational framework introduced in Chapter 3 with single cell resolution, I utilize deterministic and stochastic simulations to characterize the changes in protein production due to host-circuit coupling for a simple gene regulatory architecture. Analytical arguments and simulation results show that incorporating growth can lead to drastic changes in both the steady state and time scales for protein production at the single cell and population level. Furthermore, host-circuit coupling can induce bimodality at the population level well outside the bistable region for single cell dynamics.
Issue Date:2016-05-17
Type:Thesis
URI:http://hdl.handle.net/2142/92700
Rights Information:Copyright 2016 Andrew Blanchard
Date Available in IDEALS:2016-11-10
Date Deposited:2016-08


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