Engineering Robust Synthetic Microbial Communities for Sustainable Biotechnology Applications

Context: Microbes are found everywhere, from the soil and the seas to the our food and bodies, performing fundamental roles in nature and human health. Advances in molecular and synthetic biology have demonstrated that engineered microbes have the potential to be a crucial component in future sustainable technologies from manufacturing to medicine. Despite their potential, using single types of engineered microbes (monocultures) has limitations. There is only so far that we can push cells before they succumb to evolutionary and other pressures, and our engineering efforts are lost. It has long been proposed that division-of-labour, in which a complex and resource intensive task is divided into more manageable chunks and distributed to specialised workers, can provide the solution to monoculture limitations. Challenge: Placing different microbial strains into the same environment leads to competition for space and resources, resulting in extinction of some strains, and failure of the larger process. Strains in wild microbiomes are able to co-exist by interacting with one another, demonstrating both combative and cooperative behaviours. While some simple examples of engineered microbial communities have been created by manipulating such interactions, the ad hoc approach taken to-date has provided very little foundation on which to build communities for real applications. Aims and objectives: This project aims to move beyond ad hoc demonstrations of simple communities, to develop a deeper understanding of how the various genetic tools at our disposal can be harnessed to efficiently and effectively produce robust microbial communities for biotechnological applications. To achieve this we will: Develop a platform for the design, implementation, and assessment of synthetic microbial communities; uniquely bringing together threads from mathematical and biological disciplines, and bridging them with computational and robotic capabilities. Through rapid prototyping and iteration of new microbial communities, explore factors that contribute to community stability and resilience; propagating this knowledge back into the community design process. Demonstrate the application of this platform and knowledge to a complex bio-process; producing high-value biochemicals from sugars in a four-strain community Potential applications and benefits: The direct outputs of this project will provide immediate impact in fields such as ecology and microbiology, where existing top-down approaches to understanding community behaviours have focused on analysing wild microbiomes or assembling novel communities of wild strains. This project will deliver the tools for a systematic bottom-up approach, enabling falsification and refinement of theory that has been difficult to achieve in the past. Our proof-of-principle community bio-process, and the systematic engineering framework, will also provide short term benefits to those interested in advancing bio-industrial applications. In the longer term, we aim to use this as a foundation for understanding how engineered microbes interact with existing microbiomes; a fundamental challenge and important responsibility as we push engineering biology applications into medical and environmental settings. Given this breadth of possibility, this project will provide impact from academia to industry and broader society. Relevance to BBSRC priorities: This project aligns with the BBSRC’s goals of advancing bioscience for sustainable agriculture, health, and advanced manufacturing; providing a foundation for immediate and sustained improvement across all of these areas. It also supports UKRI’s mission to drive innovation and economic growth through cutting-edge science and technology. By addressing current limitations in microbial engineering, this project contributes to the UK government’s focus on engineering biology as a critical technology.