Summer School: Design and Control of Microbial Communities

Synthetic microbial consortia have been increasingly utilized in biotechnology. Experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, a quantitative understanding of the conditions that make stable coexistence and higher productivity possible is still limited. I present a coarse-grained mathematical model of a prototypical synthetic consortium consisting of two E. coli strains. A first strain produces a heterologous protein, while a second strain is engineered to scavenge toxic byproducts, thus favoring growth of the producer at the expense of diverting part of the resources to growth of the cleaner. The simplicity of the consortium is ideal to perform an in-depth analysis of conditions enabling stable coexistence of the strains. Moreover, it allows an analysis of the trade-offs involved in heterologous protein production by a consortium as compared to a mono-culture. I also present some initial experimental results on the growth of the E. coli consortium in a computer-controlled mini-bioreactor system.

In this talk, I will detail how we have tackled two distinct questions that have fascinated us over the past few years: do we have to understand a community to control it, and can we design a community to (robustly) control itself? I will cover the computational and mathematical approaches used and demonstrate how we can validate some of our theoretical results in the lab with synthetic biology.

We will step-by-step build quantitative ODE models of a metabolic network integrating regulation on both the metabolic and gene expression level, and investigate the effect of these layers of regulation on the networks dynamics. The course will be structured around the case of carbon catabolite repression in bacteria, using simple kinetic models. All simulations will be carried out by means of Matlab (no toolboxes needed). The hand-out and the models and simulation code are available from the instructor.