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Principles for Designing Robust and Stable Synthetic Microbial Consortia


Ren, Xinying (Cindy) (2021) Principles for Designing Robust and Stable Synthetic Microbial Consortia. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/hc8x-3280.


Engineering stable microbial consortia with robust functions are useful in many areas, including bioproduction and human health. Robust and stable properties depend on proper control of dynamics ranging from single cell-level to population-environment interactions. In this thesis, I discuss principles of building microbial consortia with synthetic circuits in two design scenarios.

First, for one microbial population, strong disturbances in environments often severely perturb cell states and lead to heterogeneous responses. Single cell-level design of control circuits may fail to induce a uniform response as needed. I demonstrate that cell-cell signaling systems can facilitate coordination among cells and achieve robust population-level behaviors. Moreover, I show that heterogeneity can be harnessed for robust adaptation at population-level via a bistable state switch.

Second, multi-pecies consortia are intrinsically unstable due to competitive exclusion. Previous theoretical investigations based on models of pairwise interactions mainly explored what interaction network topology ensures stable coexistence. Yet neglecting detailed interaction mechanisms and spatial context results in contradictory predictions. Focusing on chemical-mediated interaction, I show that detailed mechanisms of chemical consumption/accumulation and chemical-induced growth/death, interaction network topology and spatial structures of environments all are critical factors to maintain stable coexistence. With a two population-system, I demonstrate that the same interaction network topology can exhibit qualitatively different or even opposite behaviors due to interaction mechanisms and spatial conditions.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Design principles, feedback control, robustness, microbial consortia
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Control and Dynamical Systems
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Murray, Richard M.
Thesis Committee:
  • Doyle, John Comstock (chair)
  • Murray, Richard M.
  • Elowitz, Michael B.
  • Pierce, Niles A.
  • Franco, Elisa
Defense Date:1 March 2021
Record Number:CaltechTHESIS:05262021-072231177
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Chapter 2. adapted for Chapter 2. adapted for Chapter 3. adapted for Chapter 3.
Ren, Xinying (Cindy)0000-0002-8852-6722
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14175
Deposited By: Xinying Ren
Deposited On:03 Jun 2021 23:59
Last Modified:10 Jun 2021 15:49

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