Continued economic development necessitates truly sustainable approaches for addressing human needs, including the provision of food, the production of therapeutics, and the disposal of waste. Biological systems are fantastic platforms for meeting such needs, as they contain a universe of highly specific catalysts, self-replicate, undergo evolution to improve function, and integrate information about their surroundings to adjust their behavior. Outstanding progress has been made engineering single-species microbial systems, collectively enabling economical production of a wide variety of chemicals and materials from renewable sources and the construction of complex behaviors. However, natural microbial systems are rarely, if ever, composed of a single species. Rather, microbial communities containing tens to hundreds of species, richly distributed across 3D space, and enmeshed in a complex network of chemical reactions are the norm. These microbial communities exist in every known habitat, playing vital roles in human health, soil productivity, marine biogeochemistry, and even atmospheric phenomena. Strikingly, microbial communities can achieve higher metabolic efficiency than single-species systems through division of labor and compartmentalization of competing metabolic pathways, and attain increased resilience through occupancy of available niche space. Therefore, engineered microbial communities represent a disruptive paradigm through which to sustainably solve pressing challenges in food, health, and the environment.
Despite their ubiquity in nature, it is currently extremely difficult to synthetically design and assemble microbial communities which predictably colonize defined habitats and exhibit desired properties. These challenges arise for several reasons. First, engineered microbes are often quickly outcompeted by native species and therefore do not stably colonize their intended habitat. Further, few synthetic biology parts have been characterized for engineered strains colonizing microbial communities, making rational design difficult. Additionally, the metabolic capacity of engineered microbial communities must be very high in order to successfully compete for nutrients with their host and potential invaders. Finally, it is difficult to computationally predict the properties of an engineered community from its genetic content, and nearly impossible to use this predictive power for forward design.
The Crook Lab addresses these challenges through the development of new high-throughput experimental and computational genetic engineering techniques. By undertaking high-risk, basic research, we hope to uncover novel biological phenomena and accelerate applied research and development in the broad areas of metabolic engineering, synthetic biology, and microbial ecology.
Our current application focus is the human gut microbiota. The ability of the gut microbiota to influence health has recently been uncovered, enabled by high-throughput DNA sequencing and animal models in which community composition is precisely controlled. The ultimate goal of this focus is the development of foundational technologies by which engineered gut commensal ecosystems can be designed and assembled as a matter of practice, enabling the conversion of food into a healthy mixture of energy, nutrients, and therapeutics (See Figure).
Figure. An engineered gut microbiota mediates the conversion of dietary material to compounds required for host health.