Understanding and engineering complex microbial communities (360G-Wellcome-209397_Z_17_Z)

The human microbiota provides protection against pathogens via colonisation resistance. However, this resistance is not guaranteed, especially in the face of antibiotic treatment that suppresses the microbiota. My goal is to engineer communities for robustness to both antibiotics and pathogens. The challenge is that communities are complex systems containing many interacting and evolving species, making them challenging to predict and understand. Aim 1. Develop theory and analysis tools for complex microbial communities We will develop complex systems theory and quantitative tools to meet the challenges of understanding and engineering diverse communities. Aim 2. Apply theory to in-vitro gut communities We will apply our theory and test our ability to design gut communities that are robust to either antibiotic treatment, colonisation by the enteric pathogen Salmonella Typhimurium, or both. We will then study community and pathogen evolution: can a pathogen easily resist a probiotic community? Will the community evolve in response? Aim 3. Apply theory to S. Typhimurium pathogenesis We will study S. Typhimurium in gnotobiotic mice and test our ability to design robust communities in vivo. We will ask if S. Typhimurium can overcome in vivo colonisation resistance.