Detalle de: Systems Biotechnology Group

Summary

We applied a multidisciplinary approach including metabolic modelling, systems and synthetic biology to study bacterial metabolism from cellular to population level. Our final goal is to create a biological framework that allows the development of a broad range of novel and non-intuitive biotechnological processes, such as bioremediation solutions and sustainable production alternatives.

Research Lines

Increasing the completeness and scope of metabolic reconstructions

We are committed to building a niche-specific collection of standardised and highly reproducible metabolic models. In pursuit of this goal, we have dedicated ourselves to developing high-quality models for a wide range of metabolically diverse microorganisms. We place particular emphasis on expanding the scope of metabolic modelling by incorporating new modules that capture important aspects of microbial metabolism. This includes modeling the generation of endogenous reactive oxygen species, underground metabolism, metabolic heterogeneity, and condition-specific biomass production. By incorporating these additional components, we aim to enhance the accuracy and applicability of our models, enabling a deeper understanding of microbial physiology and facilitating the design of innovative biotechnological and clinical solutions.

Disentangling the driving forces behind metabolic processes

Microbial metabolism operates and evolves under the trade-off between two principles: optimality under one given condition and minimal adjustment between conditions. These principles give rise to a three-dimensional space characterised by competing objectives: growth, robustness, and adaptability. At our lab, we are dedicated to deciphering the intricate relationship between metabolic robustness, adaptability, and optimality in microbial metabolism. We seek to investigate the mechanisms underlying metabolic cycles that promote high robustness in bacteria and explore how metabolic heterogeneity contributes to microbial survival in the face of perturbations. By gaining a deeper understanding of these fundamental aspects, we aim to apply this knowledge to diverse fields such as biotechnology and clinical microbiology. Our ultimate goal is to leverage this newfound understanding to develop innovative solutions for a wide range of applications.

Main Technological Bioprocesses Developed at SBG. The group develops processes for the valorization of recalcitrant waste into high value-added products within the ONE HEALTH framework. To achieve this, we have not only developed a highly competitive iterative optimization cycle (DBTL), but we also utilize advanced microbial metabolism concepts such as division of labor and synthetic differentiation.

System level analysis and designing microbial communities

The division of labor allows an expanded complexity and functionality in microorganisms. Guided by these interesting features, our research focuses on two key objectives. Firstly, we aim to unravel the mechanisms underlying the emergence of complex capabilities within microbial populations and communities. By studying how microorganisms interact and coordinate their activities, we seek to understand the factors that contribute to their expanded functionality. Secondly, we strive to harness and engineer this supracellular-level functionality for various biotechnological and clinical applications. To achieve this, we have developed a comprehensive suite of systems biology tools and evolutionary engineering frameworks. Our research finds practical application in multiple areas. For instance, we are working towards the valorization of complex polymers like lignin and plastic wastes, aiming to develop sustainable strategies for their use. Additionally, we focus on cost-effective production of plant-based secondary metabolites and the development of animal-free, sustainable ingredients for the food, beverage and nutraceutical industries.

Developing a DNA biofoundry towards the AI-guided exploration of microbial chemical space.

We are actively involved in the development of a DNA biofoundry (CNBio) that integrates advanced automation, synthetic biology, evolutionary engineering and artificial intelligence (AI) to explore the untapped potential of microbial metabolism. Our goal is to go beyond the limited set of known biochemical transformations and uncover new metabolic pathways that can expand the metabolic space suitable for biotechnological and medical applications. Through the use of advanced automation and synthetic biology techniques, we can design and build genetic circuits and pathways in a systematic and precise manner. This allows us to engineer microorganisms with enhanced metabolic capabilities, opening up new possibilities for the production of valuable compounds. Furthermore, the AI-guided approach enables us to explore the vast chemical landscape of potential transformations and accelerate the discovery and optimization of novel microbial metabolic capabilities.

DBTL Cycle Developed at SBG: In recent years, the group has developed a highly integrative and partially automated DBTL cycle. To achieve this, we have created systems biology and artificial intelligence tools for Design and Learn, as well as novel synthetic biology tools in the Build stage to optimize pathway and strain construction. Additionally, the group has developed cutting-edge tools for evolutionary engineering and high-throughput prototyping in the Test stage.