Rules of life in CO2-driven microbial communities: Microbiome engineering for a Net Zero future

Microbial communities (often called microbiomes) are everywhere; on our skin, in our gut, in the soil we rely on to grow our food, indeed in almost every habitable environment on the planet. Members of microbiomes interact with one another in myriad ways which we are only just beginning to appreciate, thanks largely to powerful new tools at our disposal. In this ambitious, multidisciplinary project, we bring together expertise to use these tools to unearth the 'rules of life' that govern the interactions between microbial community members, with the view to develop predictive approaches that can help us to understand and control microbiome function. Drawing on low diversity communities that inhabit geothermal springs, we will interrogate the metabolic, ecological and evolutionary interactions between community members that collectively govern the conversion of CO2 into value-added products. These products span primary metabolites that result from direct microbial growth (and hold value as platform chemicals for manufacturing industries and as biofuels), as well as secondary metabolites that are not directly liked to growth but that play ill-defined roles in microbial communities, and often harbour bioactive properties of high value to society (e.g. antibiotics, anticancers). We will use synthetic biology approaches to engineer the microbiome and its metabolic pathways of interest, both as a learning tool with which to test hypotheses on metabolite production and function, and as a means to augment the CO2 bioconversion capacity of the system for future biotechnological development. In parallel, we will apply ecological and metabolic modelling approaches to continue to generate hypotheses that can be tested with our model system, and which will be integrated into new predictive tools to accurately infer function from microbiome genomic data. Crucially, these approaches will work in tandem to help resolve the microbe-microbe interactions that drive this model system, which we have deliberately chosen to maximise the success of our ambitious goals. By unravelling the rules of life in these low-diversity systems, we will take the first major step towards understanding the more complex communities that impact our ability to grow food and live healthy lives. At the same time, our project promises to deliver new ways to turn waste CO2 emissions into waste, towards a more sustainable and Net Zero future.

Microorganisms are everywhere. Despite our long-held tradition of studying them in isolation, microbial life exists not in isolation but as interdependent multi-species assemblages. Despite the profound impact microbial communities have on their environment and the technological advances in microbial genomics in recent years, the rules that govern the structure, function and stability of microbial communities are complex and only partially understood. Although a plethora of mechanisms that influence microbial communities have been identified, from metabolic priming, to inter- and intraspecific metabolic signalling and even direct antibiosis, holistic understanding has yet to be resolved in any microbial system.

Here, we will develop a novel experimental system that is complex yet tractable, enabling rich, coordinated multi-omics analysis coupled with computational modelling to deliver deep mechanistic insight. We will apply a cutting-edge toolbox of experimental, analytical, and computational approaches to reveal the rules of life in this system that will serve as a blueprint to apply to any microbiome. Crucially, we will move beyond standard metabarcoding and metagenomic approaches to encompass both chromosomal and extrachromosomal replicons. Achieving this requires a major shift from our taxonomy-focused paradigm to a functionality-focused view of microbial communities and their dynamics, and a multi-disciplinary team of experts to deliver frontier bioscience research. Together, we will deliver predictive understanding of the rules of microbial life in communities, and deploy these to engineer microbiome function for biotechnological applications.