In partial fulfillment of the requirements for the degree of

Doctor of Philosophy in Quantitative Biosciences
in the School of Physics

Raymond Copeland

Defends his thesis:

Physical Simulations of Microbial Communities Under Stress

Friday, April 25, 2025

12:00pm Eastern

Location: IBB Suddath Seminar Room (1128)

Zoom: https://gatech.zoom.us/j/7615576281

Advisor: 

Dr. Peter Yunker

School of Physics

Georgia Institute of Technology

Committee: 

Dr. JC Gumbart

School of Physics

Georgia Institute of Technology

Dr. Brian Hammer

School of Biological Sciences

Georgia Institute of Technology

Dr. Jennifer Curtis

School of Physics

Georgia Institute of Technology

Dr. Ozan Bozdag

School of Biological Sciences

Georgia Institute of Technology

Abstract:

     Microbial communities are ubiquitous in nature and profoundly impact human health, industry, and the environment; yet, the fundamental ecological and evolutionary principles governing their behavior often remain elusive and counterintuitive. This thesis investigates several critical, yet underexplored, aspects of microbial community dynamics, combining theoretical modeling, computational simulations, and experimental validations to reveal insights into how spatial structure, ecological interactions, and evolutionary pressures shape microbial populations.

First, by employing individual-based simulations and experimental validation with Vibrio cholerae, we demonstrate that spatial constraints and stochastic fluctuations significantly alter competitive outcomes. Specifically, spatially constrained environments benefit strains with slower antagonistic ability, mitigating fitness differences and potentially stabilizing microbial diversity. Next, we provide a rigorous theoretical underpinning for vertical biofilm growth by deriving a previously empirical heuristic model directly from first principles of active fluid dynamics. This analytical approach clarifies previously unexplained empirical observations and highlights the critical interplay between biological growth processes and physical constraints.

Further, we explore the ecological and evolutionary dynamics of enzyme-mediated antibiotic resistance within microbial communities, revealing counterintuitive phenomena related to enzyme efficacy. Despite lacking any metabolic cost, higher beta-lactamase enzyme efficacy paradoxically reduces competitive fitness through unintended community-wide detoxification of antibiotic environments—termed "cooperation by accident." In our next project, by employing a combination of population dynamics and genetic drift, we identify distinct evolutionary regimes, showing that increased enzyme efficacy can delay or even eliminate the selective advantage of antibiotic resistance. Additionally, we demonstrate that community-level properties, such as cell density and effective population size, significantly influence these evolutionary outcomes.

Collectively, this thesis underscores the critical necessity of considering spatial, ecological, and evolutionary contexts to understand microbial community behaviors. These findings have significant implications, particularly for antibiotic resistance management in clinical and environmental settings, highlighting the importance of expanding current practices beyond strain-specific antibiotic susceptibility tests toward more comprehensive community-level analyses.