Juan Nogales
Group Leader
Research summary
Our goal is deciphering the complexity of microbial metabolism, its evolutionary and biotechnological implications through a multidisciplinary approach. By assuming that the whole is greater than the sum of its parts, we aim to contribute to a better understanding of the emergent properties of microbial systems at subcellular, cellular and supracellular levels. We pursuit the rational re-design of these system properties towards novel biotechnological and medical applications.
Publications
García-Romero I, Nogales J, Diaz E, Santero E, Floriano B. Understanding the metabolism of the tetralin degrader Sphingopyxis granuli strain TFA through genome-scale metabolic modelling. Scientific Reports 2020; 10, 8651
Nogales J, Mueller J, Gudmundsson S, Canalejo FJ, Duque E, Monk J, Feist AM, Ramos JL , Niu W, Palsson BO. High-quality genome-scale metabolic modeling of Pseudomonas putida highlights its broad metabolic capabilities. Environ Microbiol 2020; (1):255-269
Lieven, C [… ] Nogales J. […] MEMOTE for standardized genome-scale metabolic model testing. Nat Biotechnol 2020; 38 (3), 272-276
Molina L, La Rosa R, Nogales J, Rojo F. Pseudomonas putida KT2440 metabolism undergoes sequential modifications during exponential growth in a complete medium as compounds are gradually consumed. Environ Microbiol 2019 21(7):2375-2390
García-Jiménez B, García JL, Nogales J. FLYCOP: metabolic modeling-based analysis and engineering microbial communities Bioinformatics 2018; 1;34(17):i954-i963
Monk J, Nogales J, Palsson BO. Optimizing genome-scale network reconstructionsOptimizing genome-scale network reconstructions. Nat Biotechnol. 2014 May;32(5):447-52.
Funding
2017-2024: INFRAIA-02-2017 and H2020-INFRADEV-2019-2. Industrial Biotechnology Innovation and Synthetic Biology Accelerator, IBISBA nº GA 730976 and 871118.
2019-2023: H2020-NMBP-BIO-2018-two-stage. Synthetic microbial consortia-based platform for flavonoids production using synthetic biology, SynBio4Flav nº GA 814650.
2020-2023: ERA CoBioTech, 2nd Joint Call on Biotechnologies. Microbial Conversion of lignin to monomers for bio-based plastic using synthetic biology MILIMO.
2020-2024: H2020-NMBP-BIO-CN-2019. MIXed plastics biodegradation and UPcycling using microbial communities, MIXUP nº GA 870294.
Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy‐Spanish National Research Council (SusPlast-CSIC).
Our foundational aim is the system-level understanding of microbial metabolism as a framework for developing a broad range of novel and non-intuitive biotechnological processes, ranging from industrial biotechnology to unconventional computing and living architecture. Taking advantage of metabolic modelling, systems and synthetic biology we are addressing, at different levels, the understanding and full taming of bacterial systems emergence.
Increasing the completeness and scope of metabolic reconstructions
Since we are largely committed in increasing the available computable reactome, we are involved in the high-quality metabolic modeling of a large set of metabolically diverse bacteria including P. putida KT2440, Synechocystis PCC6803, S. elongatus PCC7942, A. platensis, Azoarcus sp.CIB, S. granuli sp.TFA, P. pseudoalcaligenes CECT5344 and B. bacteriovorus HD100. This effort is enabling the system-level analysis of new metabolic processes while providing new computational test-beds for biotechnological applications. We are also interested in the inclusion of new metabolic modules and modelling approaches. Current efforts are targeted on i) the modeling of endogenous reactive oxygen species (ROS), ii) the implementation of dynamic condition-specific models and iii) the inclusion of posttranslational regulation.
System level analysis of Metabolic Robustness in bacteria
The robustness of a system is the property that allows it to maintain its functions despite external and internal perturbations. Through the metabolic modeling analysis of P. putida, we have recently identified metabolic cycles providing robustness to this bacterium. By using synthetic biology, ongoing efforts are focused on the rational engineering of such cycles under diverse biotechnological scenarios. In addition, we are increasing the metabolic robustness of P. putida by expanding its metabolic performance under oxygen limitation.
System level analysis and designing of microbial communities
The division of labor in microbial consortia allows an expanded complexity and functionality in bacteria. We are interested in: i) understanding how these expanded capabilities emerge within a community and ii) how we can engineer this community-level functionality towards biotechnological endeavors. To address these two fundamental questions we have developed a computational platform for modeling and engineering synthetic microbial consortia. Further implementation of these model-based designs is allowing us to develop new synthetic biology tools suitable for engineering microbial communities.
Systems metabolic modeling and engineering platform developed by SBG.
Multitasks synthetic microbial consortia being developed by SBG in the context of Living Architecture project http://livingarchitecture-h2020.eu/
