ENGINEERING SYNTHETIC MICROBIAL COMMUNITIES FOR BIOTECHNOLOGY

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In nature, microorganisms live in communities -microbiota- where each member interacts with the others and with the environment. These microbial consortia are responsible for human, animal and crop health, ecological stability, and industrial bioprocesses. For example, in the recent years, human gut microbiota has been associated with many important diseases from cardiovascular diseases to diabetes. As another example, the most stable and robust industrial bioprocesses are carried out by microbial communities, such as the production of most fermented food and drink. Despite the very well known importance of microbiota, and our recent progress towards the identification of the members of the communities we still know very little about how these communities are established and maintained, which limit our possibilities to engineer them in order to tackle microbiota diseases or create new robust bioprocesses. To this end, there is significant interest in developing simplified microbial communities which can serve as a platform to address basic biological questions on microbial interactions and to create more efficient bioprocesses than those based on a single engineered microorganism. The work proposed here aims to design and build synthetic microbial communities using synthetic biology. Synthetic biology uses engineering principles in biological systems in a predictable, controllable and standardized manner in order to get new biological insights and create cells with improved abilities. This project, firstly, will generate stable synthetic microbial communities, and secondly, will use some of these communities to perform specific tasks, such as the production of biofuels and pharmaceuticals. This work will, therefore, be able to produce specialist strains valuable for use in biotechnology.To achieve these goals, I plan to use knowledge and tools gained from my previous experiences in microbial metabolite exchange, which is the basis for establishing communities. Engineering metabolism has proven useful to generate synthetic communities, as shown by my preliminary results and previous works, indicating the feasibility of the proposed work. Therefore, we will create a series of engineered microbial strains that are able to interact with each other in different manners and generate stable communities. In addition, the generated synthetic microbial communities will be used to create more complex population behaviours and learn by building how natural communities interact and evolve. This way, we will be able to control the abundance of the members in the population, we will generate new population-level functionalities, and we will re-create ecological relationships found in nature. This will generate important new insights for understanding how cells form and maintain microbiota.Finally, we will prove that synthetic microbial communities can be designed and build to improve the production of biotechnologically relevant compounds. Firstly, a community where two microorganisms cooperate to maximize the production of an industrial pharmaceutical will be engineered. Secondly, a community designed to select the best mutants to produce biodiesel will be generated and used. Both strategies are strongly supported by competitive industrial partners in the field, which indicates the enormous potential of this new technology. This project is, therefore, developing a new synthetic biology technology that can be used in a variety of fields, from helping us to better understand natural microbiota and tackle the associated diseases to create more robust and versatile bioprocesses, which may allow us to move towards the bioeconomy.